The DOI matches its Crossref record; 341 of the 341 references it cites were found in a registry or an index; none of the 340 sources its claims cite is checked for support yet.
Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders
Open accessAbstract
Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are cognitive disorders with complex genetic architectures but overlapping behavioral phenotypes, which suggests common pathway perturbations. Multiple lines of evidence implicate imbalances in excitatory and inhibitory activity (E/I imbalance) as a shared pathophysiological mechanism. Thus, understanding the molecular underpinnings of E/I imbalance may provide essential insight into the etiology of these disorders and may uncover novel targets for future drug discovery. Here, we review key genetic, physiological, neuropathological, functional, and pathway studies that suggest alterations to excitatory/inhibitory circuits are keys to ASD and SCZ pathogenesis.
Overview
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TL;DR
This review argues that autism spectrum disorder (ASD) and schizophrenia (SCZ), despite distinct genetic architectures, converge on disrupted excitatory/inhibitory (E/I) balance in cortical circuits. It synthesizes genetic, postmortem, physiological, and animal-model evidence for shared glutamatergic and GABAergic mechanisms, including mTOR and NMDA receptor pathways.
Key findings
- E/I ratios are developmentally and cell-type specific: cultured hippocampal pyramidal dendrites shift from 2:1 at 14 days to 4:1 at 19 days, while hippocampal parvalbumin and calretinin interneurons show 14:1 and 3:1 ratios, respectively.
- In SCZ, postmortem work links gray matter loss and reduced spine density in dorsolateral prefrontal cortex, auditory cortex, and hippocampus to working memory, hallucination, and memory deficits; PV+ interneurons show lower parvalbumin and GAD67 mRNA without loss of cell number, and gamma oscillations (30–80 Hz) are abnormal.
- In ASD, early brain overgrowth occurs in about 25–30% of children between years 1 and 2, epilepsy in about 30%, and postmortem tissue shows increased spine density in some cortical layers but also contradictory simplified dendrites; GABAergic markers (GAD65/GAD67, GABA receptors, PV+ interneurons) are altered.
- Shared risk genes and pathways include NRG1/ErbB4, DISC1, 22q11 deletion, neurexins/neuroligins, SHANK, MeCP2, FMRP, CNTNAP2, mTOR, and NMDAR hypofunction; 22q11 deletion accounts for up to 1–2% of SCZ cases, and Rett syndrome has epilepsy in 80% of cases.
Methods
- Narrative review with no primary experiments; synthesizes genetic linkage/GWAS, postmortem neuropathology, electrophysiology, imaging, and mouse/animal model studies.
- Organizes evidence by disorder and circuit: SCZ and ASD separately across glutamatergic and GABAergic systems, then convergent mTOR and NMDAR signaling pathways.
- No systematic search, inclusion criteria, or meta-analysis described.
Limitations
- Authors caution that ASD postmortem evidence is limited by small samples (about 120 brains since 1980) and lack of closely matched controls; syndromic autism models (TSC, PTEN, FXS, Rett) are genetically and pathologically distinct from idiopathic autism, so their mechanisms may not fully generalize.
- Authors note unresolved discrepancies, such as ErbB4 pre- versus postsynaptic localization and NL4 synaptic localization.
- Evident from the text: conclusions rely heavily on animal models and narrative synthesis; many genetic associations are weak and heterogeneous, with individual genes explaining little risk.
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215 Not checked yet · 43 Own interpretation · 12 No basis given · 1 Own method
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In the paper
“Here, we review key genetic, physiological, neuropathological, functional, and pathway studies that suggest alterations to excitatory/inhibitory circuits are keys to ASD and SCZ pathogenesis.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > Abstract
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In the paper
“Multiple lines of evidence implicate imbalances in excitatory and inhibitory activity (E/I imbalance) as a shared pathophysiological mechanism.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > Abstract
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“Moreover, given the conditions’ heterogeneous natures, many studies lack the required power to consistently reproduce these weak associations [5].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [5] Owen MJ Williams NM O’Donovan MC The molecular genetics of schizophrenia: new findings promise new insights Mol Psychiatry 2004 9 1 14 27 14581932
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“One of the defining neuropathological features of SCZ is gray matter loss [51–53].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
What the sources say
- Not checked yetcites [51] Selemon LD Goldman-Rakic PS The reduced neuropil hypothesis: a circuit based model of schizophrenia Biological psychiatry 1999 45 1 17 25 9894571
- Not checked yetcites [52] Thompson PM Vidal C Giedd JN Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia Proceedings of the National Academy of Sciences of the United States of America 2001 98 20 11650 5 11573002 PMC58784
- Not checked yetcites [53] Vita A De Peri L Deste G Sacchetti E Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies Transl Psychiatry 2012 2 e190 23168990 PMC3565772
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“In addition, subsets of autism patients have auditory and visual hallucinations, similarly to acutely ill patients with SCZ [8].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [8] Toal F Bloemen OJ Deeley Q Psychosis and autism: magnetic resonance imaging study of brain anatomy Br J Psychiatry 2009 194 5 418 25 19407271
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“In addition, postmortem studies have discovered structural/functional changes in both glutamatergic excitatory and GABAergic inhibitory circuits in individuals with ASD and SCZ [12–14].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [12] Chattopadhyaya B Cristo GD GABAergic circuit dysfunctions in neurodevelopmental disorders Front Psychiatry 2012 3 51 22666213 PMC3364508
- Not checked yetcites [13] Glausier JR Lewis DA Dendritic spine pathology in schizophrenia Neuroscience 2013 251 90 107 22546337 PMC3413758
- Not checked yetcites [14] Hutsler JJ Zhang H Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders Brain Res 2010 1309 83 94 19896929
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In the paper
“Thus, in response to outside influences forcibly altering activity, compensatory mechanisms are recruited to restore the initial circuit set point.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
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“mice deficient in NRG1 (type III) show reductions in spine density in hippocampal neurons [85].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [85] Chen YJ Johnson MA Lieberman MD Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components J Neurosci 2008 28 27 6872 83 18596162 PMC2728592
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“Postmortem studies have examined brain regions showing the highest indices of gray matter loss and have consistently found reductions in spine density in these parts.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
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“Finally, reductions in hippocampal volume and reduced spine density on CA3 dendrites in SCZ [56, 57] could be the physiological reason why patients have problems with memory and spatial learning.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
What the sources say
- Not checked yetcites [56] Steen RG Mull C McClure R Hamer RM Lieberman JA Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies Br J Psychiatry 2006 188 510 8 16738340
- Not checked yetcites [57] Kolomeets NS Orlovskaya DD Rachmanova VI Uranova NA Ultrastructural alterations in hippocampal mossy fiber synapses in schizophrenia: a postmortem morphometric study Synapse 2005 57 1 47 55 15858835
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“Moreover, optogenetic manipulation of specific excitatory and inhibitory circuits directly caused changes in social and cognitive behavior in mice [48].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
What the sources say
- Not checked yetcites [48] Yizhar O Fenno LE Prigge M Neocortical excitation/inhibition balance in information processing and social dysfunction Nature 2011 477 7363 171 8 21796121 PMC4155501
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In the paper
“These observations suggest that while the genetics are diverse, the two diseases may convergence upon common pathophysiological mechanisms.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
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In the paper
“Collectively, these studies reveal strong associations between brain region-specific loss of gray matter, reduced spine density and functional hypoactivity in SCZ.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
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“Fittingly, gamma-frequency oscillations are abnormal in the prefrontal cortex of patients with SCZ who are performing working-memory tasks [45, 62, 63].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
What the sources say
- Not checked yetcites [45] Uhlhaas PJ Singer W Abnormal neural oscillations and synchrony in schizophrenia Nat Rev Neurosci 2010 11 2 100 13 20087360
- Not checked yetcites [62] Haenschel C Bittner RA Waltz J Cortical oscillatory activity is critical for working memory as revealed by deficits in early-onset schizophrenia J Neurosci 2009 29 30 9481 9 19641111 PMC6666530
- Not checked yetcites [63] Barr MS Farzan F Tran LC Chen R Fitzgerald PB Daskalakis ZJ Evidence for excessive frontal evoked gamma oscillatory activity in schizophrenia during working memory Schizophr Res 2010 121 1–3 146 52 20598857
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“Information transfer in the brain relies on a functional balance between excitatory and inhibitory networks.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
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In the paper
“Dysfunction of DLPFC inhibitory PV+ basket cells is also thought to play a major role in SCZ’s working memory deficits.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
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In the paper
“In conclusion, these findings suggest hyper-excitability and gamma wave disruption in particular brain regions can be etiological contributions of SCZ.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
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In the paper
“However, this ratio is highly asymmetric across development and between neuronal subtypes.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
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“Spine loss in the DLPFC has been reproducibly reported, particularly in layer 3 neurons [54].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
What the sources say
- Not checked yetcites [54] Glantz LA Lewis DA Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia Arch Gen Psychiatry 2000 57 1 65 73 10632234
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“Moreover, there is also a profound reduction in spine density on pyramidal neurons in the primary auditory cortex, which could explain why schizophrenics suffer from auditory hallucinations [55].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
What the sources say
- Not checked yetcites [55] Sweet RA Henteleff RA Zhang W Sampson AR Lewis DA Reduced dendritic spine density in auditory cortex of subjects with schizophrenia Neuropsychopharmacology 2009 34 2 374 89 18463626 PMC2775717
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“Thus, the E/I synaptic ratio is critical for keeping the cell’s overall firing patterns within a narrow range [36].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
What the sources say
- Not checked yetcites [36] Eichler SA Meier JC E-I balance and human diseases - from molecules to networking Front Mol Neurosci 2008 1 2 18946535 PMC2526001
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In the paper
“As spiny synapses are the basic units of excitatory neural circuits and are intimately involved in neurotransmitter signal transduction, dendritic spine dysfunction may play an important etiological role in SCZ.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT
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“Indeed, long-term DISC1 knockdown leads to reduced spine area in cortical neurons [103].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [103] Hayashi-Takagi A Takaki M Graziane N Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1 Nat Neurosci 2010 13 3 327 32 20139976 PMC2846623
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In the paper
“several case studies have found smaller neurons and simplified dendrite morphology in the limbic system, consistent with a curtailment of developmental maturity [140, 141].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [140] Guerin P Lyon G Barthelemy C Neuropathological study of a case of autistic syndrome with severe mental retardation Dev Med Child Neurol 1996 38 3 203 11 8631517
- Not checked yetcites [141] Raymond GV Bauman ML Kemper TL Hippocampus in autism: a Golgi analysis Acta Neuropathol 1996 91 1 117 9 8773156
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In the paper
“3) ErbB4 is not necessary for excitatory transmission between pyramidal neurons [87].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [87] Fazzari P Paternain AV Valiente M Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling Nature 2010 464 7293 1376 80 20393464
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“Primary hippocampal neurons from mice engineered to carry hemizygous deletion of the 1.3-Mb orthologous chromosomal region (Df(16)A+/−) showed reduced spine density and sizes [107].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > 22q11 microdeletion
What the sources say
- Not checked yetcites [107] Mukai J Dhilla A Drew LJ Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion Nat Neurosci 2008 11 11 1302 10 18836441 PMC2756760
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In the paper
“Through multiple mRNA studies, it has been established that ErbB4 is expressed predominantly in GABAergic cells in the neocortex and hippocampus [115–119].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [115] Lai C Lemke G An extended family of protein-tyrosine kinase genes differentially expressed in the vertebrate nervous system Neuron 1991 6 5 691 704 2025425
- Not checked yetcites [116] Steiner H Blum M Kitai ST Fedi P Differential expression of ErbB3 and ErbB4 neuregulin receptors in dopamine neurons and forebrain areas of the adult rat Exp Neurol 1999 159 2 494 503 10506520
- Not checked yetcites [117] Gerecke KM Wyss JM Karavanova I Buonanno A Carroll SL ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system J Comp Neurol 2001 433 1 86 100 11283951
- Not checked yetcites [118] Fox IJ Kornblum HI Developmental profile of ErbB receptors in murine central nervous system: implications for functional interactions J Neurosci Res 2005 79 5 584 97 15682390
- Not checked yetcites [119] Thompson M Lauderdale S Webster MJ Widespread expression of ErbB2, ErbB3 and ErbB4 in non-human primate brain Brain Res 2007 1139 95 109 17280647
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In the paper
“Indeed, fMRI studies have consistently reported patterns of long-distance “under connectivity” with short-range “over connectivity” in brains of ASD adult patients [144].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [144] Wass S Distortions and disconnections: disrupted brain connectivity in autism Brain Cogn 2011 75 1 18 28 21055864
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In the paper
“Evidence for alterations in GABAergic circuits in ASD also come from postmortem studies showing significantly reduced GAD65/GAD67 levels in the parietal cortex and cerebellum [145, 146]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [145] Fatemi SH Halt AR Stary JM Kanodia R Schulz SC Realmuto GR Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in autistic parietal and cerebellar cortices Biological psychiatry 2002 52 8 805 10 12372652
- Not checked yetcites [146] Yip J Soghomonian JJ Blatt GJ Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications Acta Neuropathol 2007 113 5 559 68 17235515
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“recent evidence examining post-mortem ASD human brain tissue revealed an increase in spine density on apical dendrites of pyramidal neurons from cortical layer 2 in frontal, temporal and parietal lobes and layer 5 in the temporal lobe [14].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [14] Hutsler JJ Zhang H Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders Brain Res 2010 1309 83 94 19896929
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In the paper
“Interestingly, loss of either of two genes within this region (ZDHHC8 and DGCR8) was sufficient to impair spine and dendrite morphology [106, 107].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > 22q11 microdeletion
What the sources say
- Not checked yetcites [106] Stark KL Xu B Bagchi A Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model Nat Genet 2008 40 6 751 60 18469815
- Not checked yetcites [107] Mukai J Dhilla A Drew LJ Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion Nat Neurosci 2008 11 11 1302 10 18836441 PMC2756760
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In the paper
“multiple postmortem studies show schizophrenic adults have lower levels of GAD67 in DLPFC PV+ neurons [65, 113, 114]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT
What the sources say
- Not checked yetcites [65] Hashimoto T Volk DW Eggan SM Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia J Neurosci 2003 23 15 6315 26 12867516 PMC6740534
- Not checked yetcites [113] Volk DW Austin MC Pierri JN Sampson AR Lewis DA Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyric acid neurons in subjects with schizophrenia Arch Gen Psychiatry 2000 57 3 237 45 10711910
- Not checked yetcites [114] Akbarian S Kim JJ Potkin SG Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics Arch Gen Psychiatry 1995 52 4 258 66 7702443
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None of the sources cited for this claim have been checked yet.
In the paper
“Gamma oscillation amplitudes are reduced in patients with SCZ [111, 112]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT
What the sources say
- Not checked yetcites [111] Kwon JS O’Donnell BF Wallenstein GV Gamma frequency-range abnormalities to auditory stimulation in schizophrenia Arch Gen Psychiatry 1999 56 11 1001 5 10565499 PMC2863027
- Not checked yetcites [112] Wilson TW Hernandez OO Asherin RM Teale PD Reite ML Rojas DC Cortical gamma generators suggest abnormal auditory circuitry in early-onset psychosis Cereb Cortex 2008 18 2 371 8 17557901 PMC2648842
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Kalirin loss strongly correlates with spine loss in layer 3 prefrontal cortex neurons in postmortem schizophrenia samples [104].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [104] Hill JJ Hashimoto T Lewis DA Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia Mol Psychiatry 2006 11 6 557 66 16402129
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“and alterations in GABAA and GABAB receptors in postmortem brains of autistic subjects [147–149].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [147] Collins AL Ma D Whitehead PL Investigation of autism and GABA receptor subunit genes in multiple ethnic groups Neurogenetics 2006 7 3 167 74 16770606 PMC1513515
- Not checked yetcites [148] Fatemi SH Reutiman TJ Folsom TD Thuras PD GABA(A) receptor downregulation in brains of subjects with autism J Autism Dev Disord 2009 39 2 223 30 18821008 PMC2697059
- Not checked yetcites [149] Oblak AL Gibbs TT Blatt GJ Decreased GABA(B) receptors in the cingulate cortex and fusiform gyrus in autism J Neurochem 2010 114 5 1414 23 20557420 PMC2923229
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“About 25–30% of autistic children experience excessive increase in brain size between the first and second year of life when compared with healthy controls [137]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [137] Courchesne E Redcay E Kennedy DP The autistic brain: birth through adulthood Curr Opin Neurol 2004 17 4 489 96 15247547
plain- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Dysbindin is involved with intracellular trafficking and is downregulated in the prefrontal cortex and hippocampus of SCZ patients [132, 133].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > DISC1/Dysbindin
What the sources say
- Not checked yetcites [132] Weickert CS Straub RE McClintock BW Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain Arch Gen Psychiatry 2004 61 6 544 55 15184234
- Not checked yetcites [133] Talbot K Eidem WL Tinsley CL Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia J Clin Invest 2004 113 9 1353 63 15124027 PMC398430
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“culture studies have shown that particular splice variants influence the formation of specific synapses [158, 177–180].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [158] Chih B Gollan L Scheiffele P Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex Neuron 2006 51 2 171 8 16846852
- Not checked yetcites [177] Boucard AA Chubykin AA Comoletti D Taylor P Sudhof TC A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins Neuron 2005 48 2 229 36 16242404
- Not checked yetcites [178] Graf ER Kang Y Hauner AM Craig AM Structure function and splice site analysis of the synaptogenic activity of the neurexin-1 beta LNS domain J Neurosci 2006 26 16 4256 65 16624946 PMC2826202
- Not checked yetcites [179] Dean C Scholl FG Choih J Neurexin mediates the assembly of presynaptic terminals Nat Neurosci 2003 6 7 708 16 12796785 PMC1646425
- Not checked yetcites [180] Koehnke J Katsamba PS Ahlsen G Splice form dependence of beta-neurexin/neuroligin binding interactions Neuron 2010 67 1 61 74 20624592 PMC2910870
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“conversely, knockdowns lead to excitatory synapse loss [163, 167, 186–188].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [163] Kwon HB Kozorovitskiy Y Oh WJ Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number Nat Neurosci 2012 15 12 1667 74 23143522 PMC3536444
- Not checked yetcites [167] Zhang C Milunsky JM Newton S A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export J Neurosci 2009 29 35 10843 54 19726642 PMC2777970
- Not checked yetcites [186] Chih B Afridi SK Clark L Scheiffele P Disorder-associated mutations lead to functional inactivation of neuroligins Hum Mol Genet 2004 13 14 1471 7 15150161
- Not checked yetcites [187] Chih B Engelman H Scheiffele P Control of excitatory and inhibitory synapse formation by neuroligins Science 2005 307 5713 1324 8 15681343
- Not checked yetcites [188] Chubykin AA Atasoy D Etherton MR Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2 Neuron 2007 54 6 919 31 17582332 PMC3738748
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Multiple studies have identified rare mutations and CNVs in genes encoding synaptic proteins in autistic individuals, supporting the hypothesis that excitatory synapse dysfunction may be important in the etiology of ASD.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Nrxn-NL trans-synaptic signaling recruits NMDARs and AMPARs to the synapse surface, possibly via intracellular mechanisms centered around the PSD-95 scaffold [185]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [185] Dalva MB McClelland AC Kayser MS Cell adhesion molecules: signalling functions at the synapse Nat Rev Neurosci 2007 8 3 206 20 17299456 PMC4756920
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“More recently, a genome-wide copy number variation analysis also implicated NLGN1 among several candidate genes in ASD susceptibility [176].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [176] Glessner JT Wang K Cai G Autism genome-wide copy number variation reveals ubiquitin and neuronal genes Nature 2009 459 7246 569 73 19404257 PMC2925224
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“a transgenic mouse overexpressing NL1 also had disruptions in memory acquisition and LTP, but this time as a result of increased numbers of excitatory synapses [193].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [193] Dahlhaus R Hines RM Eadie BD Overexpression of the cell adhesion protein neuroligin-1 induces learning deficits and impairs synaptic plasticity by altering the ratio of excitation to inhibition in the hippocampus Hippocampus 2010 20 2 305 22 19437420
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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In the paper
“a NLGN1-knockout mouse exhibited deficits in spatial memory and increased repetitive behavior as a result of decreased long-term synaptic plasticity in area CA1 of the hippocampus and dorsal striatum [192].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [192] Blundell J Blaiss CA Etherton MR Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior J Neurosci 2010 30 6 2115 29 20147539 PMC2824441
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“over-expression of these NL isoforms increased excitatory synapse number and spine density in cultured neurons”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [163] Kwon HB Kozorovitskiy Y Oh WJ Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number Nat Neurosci 2012 15 12 1667 74 23143522 PMC3536444
- Not checked yetcites [167] Zhang C Milunsky JM Newton S A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export J Neurosci 2009 29 35 10843 54 19726642 PMC2777970
- Not checked yetcites [186] Chih B Afridi SK Clark L Scheiffele P Disorder-associated mutations lead to functional inactivation of neuroligins Hum Mol Genet 2004 13 14 1471 7 15150161
- Not checked yetcites [187] Chih B Engelman H Scheiffele P Control of excitatory and inhibitory synapse formation by neuroligins Science 2005 307 5713 1324 8 15681343
- Not checked yetcites [188] Chubykin AA Atasoy D Etherton MR Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2 Neuron 2007 54 6 919 31 17582332 PMC3738748
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“another study showed that ASD patient brains had lower numbers of PV+ interneurons in the prefrontal cortex [151].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [151] Zikopoulos B Barbas H Altered neural connectivity in excitatory and inhibitory cortical circuits in autism Front Hum Neurosci 2013 7 609 24098278 PMC3784686
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“In vitro and in vivo studies show NL1, NL3, and NL4 localize to excitatory synapses [182–184]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [182] Song JY Ichtchenko K Sudhof TC Brose N Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses Proceedings of the National Academy of Sciences of the United States of America 1999 96 3 1100 5 9927700 PMC15357
- Not checked yetcites [183] Budreck EC Scheiffele P Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses Eur J Neurosci 2007 26 7 1738 48 17897391
- Not checked yetcites [184] Graf ER Zhang X Jin SX Linhoff MW Craig AM Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins Cell 2004 119 7 1013 26 15620359 PMC2826211
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“also exhibited increases in grooming behaviors [181].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [181] Etherton MR Blaiss CA Powell CM Sudhof TC Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments Proceedings of the National Academy of Sciences of the United States of America 2009 106 42 17998 8003 19822762 PMC2764944
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“the NL3 Arg451Cys, NL4 D396X, and NL4 R87W variants - missense mutations found in affected in autistic members of several families - prevented this effect due to surface trafficking defects”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [163] Kwon HB Kozorovitskiy Y Oh WJ Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number Nat Neurosci 2012 15 12 1667 74 23143522 PMC3536444
- Not checked yetcites [167] Zhang C Milunsky JM Newton S A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export J Neurosci 2009 29 35 10843 54 19726642 PMC2777970
- Not checked yetcites [186] Chih B Afridi SK Clark L Scheiffele P Disorder-associated mutations lead to functional inactivation of neuroligins Hum Mol Genet 2004 13 14 1471 7 15150161
- Not checked yetcites [187] Chih B Engelman H Scheiffele P Control of excitatory and inhibitory synapse formation by neuroligins Science 2005 307 5713 1324 8 15681343
- Not checked yetcites [188] Chubykin AA Atasoy D Etherton MR Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2 Neuron 2007 54 6 919 31 17582332 PMC3738748
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“NLGN4-knockouts exhibit highly selective deficits in social interactions and communication [194, 195].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [194] Radyushkin K Hammerschmidt K Boretius S Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit Genes, brain, and behavior 2009 8 4 416 25 19243448
- Not checked yetcites [195] Jamain S Radyushkin K Hammerschmidt K Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism Proceedings of the National Academy of Sciences of the United States of America 2008 105 5 1710 5 18227507 PMC2234209
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a small population of NL2 is also endogenously present in excitatory synapses”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [224] Hines RM Wu L Hines DJ Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression J Neurosci 2008 28 24 6055 67 18550748 PMC6670530
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“NL2 tightly regulates inhibitory synapse architecture and function by tethering pre-synaptic α-Nrxns or a subset of β-Nrxns with an insert in splice site 4 [158].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [158] Chih B Gollan L Scheiffele P Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex Neuron 2006 51 2 171 8 16846852
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the relevance of specific molecular mechanisms and cellular alterations to pure autism may not be entirely accurate.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“epilepsy is co-morbid in 80% of cases of Rett Syndrome”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [230] Jian L Nagarajan L de Klerk N Predictors of seizure onset in Rett syndrome J Pediatr 2006 149 4 542 7 17011329
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, NL3 R451C mutation causes region-specific alterations in either excitatory or inhibitory neural circuits that accompany the ASD-relevant mouse behaviors.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Fragile X syndrome results from transcriptional silencing of the FMR1 gene, which encodes for the transcription regulator FMRP”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [217] Bagni C Greenough WT From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome Nat Rev Neurosci 2005 6 5 376 87 15861180
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Functional studies have linked neuroligin 2 (NL2) to proper inhibitory synaptic function [188, 222].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [188] Chubykin AA Atasoy D Etherton MR Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2 Neuron 2007 54 6 919 31 17582332 PMC3738748
- Not checked yetcites [222] Varoqueaux F Jamain S Brose N Neuroligin 2 is exclusively localized to inhibitory synapses Eur J Cell Biol 2004 83 9 449 56 15540461
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“additional studies unexpectedly revealed a large increase in excitatory transmission in the hippocampus [196].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [196] Etherton M Foldy C Sharma M Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function Proceedings of the National Academy of Sciences of the United States of America 2011 108 33 13764 9 21808020 PMC3158170
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“NLGN4-knockout mice are accurate models of certain monogenic heritable ASDs [195]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [195] Jamain S Radyushkin K Hammerschmidt K Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism Proceedings of the National Academy of Sciences of the United States of America 2008 105 5 1710 5 18227507 PMC2234209
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“maternal duplications of chromosome 15q11-q13, a region that encompasses the Angelman syndrome gene UBE3A, are associated with autism [219].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [219] Cook EH Jr Lindgren V Leventhal BL Autism or atypical autism in maternally but not paternally derived proximal 15q duplication Am J Hum Genet 1997 60 4 928 34 9106540 PMC1712464
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Converging evidence from genetic and neuropathological studies suggest pathological cellular alterations to GABAergic interneurons may play etiological roles in ASD.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These mice, similar to the NLGN2-overexpression mice, also exhibited impaired social interactions.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [225] Tabuchi K Blundell J Etherton MR A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice Science 2007 318 5847 71 6 17823315 PMC3235367
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting a potential link between Angelman syndrome, autism and altered synaptic structure.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“NLGN2-overexpressing mice also exhibit small but significant changes in excitatory synapse morphology [224]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [224] Hines RM Wu L Hines DJ Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression J Neurosci 2008 28 24 6055 67 18550748 PMC6670530
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“UBE3A encodes an E3 ubiquitin ligase whose loss reduces dendritic spine density and length in cerebellar and hippocampal pyramidal neurons [220, 221]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [220] Dindot SV Antalffy BA Bhattacharjee MB Beaud The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology Hum Mol Genet 2008 17 1 111 8 17940072
- Not checked yetcites [221] Greer PL Hanayama R Bloodgood BL The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc Cell 2010 140 5 704 16 20211139 PMC2843143
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“individuals harboring mutations of tuberous sclerosis proteins 1 and 2 (TSC1, TSC2) or the phosphatase and tensin homolog (PTEN) gene are frequently diagnosed with autism [211, 212].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [211] Prather P de Vries PJ Behavioral and cognitive aspects of tuberous sclerosis complex J Child Neurol 2004 19 9 666 74 15563012
- Not checked yetcites [212] Butler MG Dasouki MJ Zhou XP Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations J Med Genet 2005 42 4 318 21 15805158 PMC1736032
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Shank3 interacts with the NLs through PSD95 and GKAP”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
What the sources say
- Not checked yetcites [154] Sudhof TC Neuroligins and neurexins link synaptic function to cognitive disease Nature 2008 455 7215 903 11 18923512 PMC2673233
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the R451C mutation may lead to a gain-of-function shift of NL3 activity to the inhibitory synapse”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting NL2 may also have some overlapping and redundant functions at the excitatory synapse.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“MECP2-null mice exhibit most of the neurological phenotypes of Rett syndrome [231, 232]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [231] Guy J Hendrich B Holmes M Martin JE Bird A A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome Nat Genet 2001 27 3 322 6 11242117
- Not checked yetcites [232] Chen RZ Akbarian S Tudor M Jaenisch R Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice Nat Genet 2001 27 3 327 31 11242118
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“TSC1 or TSC2 loss causes enlarged spines [214].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [214] Tavazoie SF Alvarez VA Ridenour DA Kwiatkowski DJ Sabatini BL Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2 Nat Neurosci 2005 8 12 1727 34 16286931
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“MeCP2, a transcriptional regulator that is mutated in Rett syndrome, controls the function of excitatory synapses and spine morphology in an activity-dependent manner [218].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [218] Zhou Z Hong EJ Cohen S Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation Neuron 2006 52 2 255 69 17046689 PMC3962021
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“mTOR activity becomes essential during this time by controlling key components of homeostasis such as synaptogenesis, spinogenesis, and dendrite arborization [270].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
What the sources say
- Not checked yetcites [270] Lasarge CL Danzer SC Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation Front Mol Neurosci 2014 7 18 24672426 PMC3953715
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which recapitulates the corticostriato-thalamic circuitry known to control higher order functions such as speech and language.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“GABAergic abnormalities in the thalamus [234] and medulla [235] occur in MECP2-null mice prior symptom onset.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [234] Zhang ZW Zak JD Liu H MeCP2 is required for normal development of GABAergic circuits in the thalamus J Neurophysiol 2010 103 5 2470 81 20200124 PMC2867574
- Not checked yetcites [235] Medrihan L Tantalaki E Aramuni G Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome J Neurophysiol 2008 99 1 112 21 18032561
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Around 20% of those with FXS meet formal criteria for an ASD [239–242]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [239] Clifford S Dissanayake C Bui QM Huggins R Taylor AK Loesch DZ Autism spectrum phenotype in males and females with fragile X full mutation and premutation J Autism Dev Disord 2007 37 4 738 47 17031449
- Not checked yetcites [240] Harris SW Hessl D Goodlin-Jones B Autism profiles of males with fragile X syndrome Am J Ment Retard 2008 113 6 427 38 19127654 PMC2629645
- Not checked yetcites [241] Hatton DD Sideris J Skinner M Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP Am J Med Genet A 2006 140A 17 1804 13 16700053
- Not checked yetcites [242] Wang LW Berry-Kravis E Hagerman RJ Fragile X: leading the way for targeted treatments in autism Neurotherapeutics 2010 7 3 264 74 20643379 PMC4084556
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Loss of MeCP2 leads to inhibitory neurons containing lower than normal levels of GABA”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [233] Chao HT Chen H Samaco RC Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes Nature 2010 468 7321 263 9 21068835 PMC3057962
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting these effects may involve region-specific gamma oscillation deficiencies [246].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [246] Selby L Zhang C Sun QQ Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein Neurosci Lett 2007 412 3 227 32 17197085 PMC1839948
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“MeCP2 controls the expression of GAD65 and GAD67 in GABAergic neurons in a cell-autonomous manner [233].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [233] Chao HT Chen H Samaco RC Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes Nature 2010 468 7321 263 9 21068835 PMC3057962
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“FXS specifically exhibit profound network hyperexcitability in the amygdala - an area of the brain responsible for emotional processing - due to the loss of GAD65 and GAD67 expression and reduced GABAergic synapses [244].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [244] Olmos-Serrano JL Paluszkiewicz SM Martin BS Kaufmann WE Corbin JG Huntsman MM Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome J Neurosci 2010 30 29 9929 38 20660275 PMC2948869
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“various other reports discovered region-specific increases or decreases of GAD 65/67 levels [244, 248–251].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [244] Olmos-Serrano JL Paluszkiewicz SM Martin BS Kaufmann WE Corbin JG Huntsman MM Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome J Neurosci 2010 30 29 9929 38 20660275 PMC2948869
- Not checked yetcites [248] D’Hulst C Heulens I Brouwer JR Expression of the GABAergic system in animal models for fragile X syndrome and fragile X associated tremor/ataxia syndrome (FXTAS) Brain Res 2009 1253 176 83 19070606
- Not checked yetcites [249] Adusei DC Pacey LK Chen D Hampson DR Early developmental alterations in GABAergic protein expression in fragile X knockout mice Neuropharmacology 2010 59 3 167 71 20470805
- Not checked yetcites [250] El Idrissi A Ding XH Scalia J Trenkner E Brown WT Dobkin C Decreased GABA(A) receptor expression in the seizure-prone fragile X mouse Neurosci Lett 2005 377 3 141 6 15755515
- Not checked yetcites [251] Paluszkiewicz SM Martin BS Huntsman MM Fragile X syndrome: the GABAergic system and circuit dysfunction Dev Neurosci 2011 33 5 349 64 21934270 PMC3254035
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that it is involved interneuron function.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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None of the sources cited for this claim have been checked yet.
In the paper
“Genetic studies over the past decade have reproducibly associated CNTNAP2 variants with ASD [252–256].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
What the sources say
- Not checked yetcites [252] Bakkaloglu B O’Roak BJ Louvi A Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders Am J Hum Genet 2008 82 1 165 73 18179895 PMC2253974
- Not checked yetcites [253] Rossi E Verri AP Patricelli MG A 12Mb deletion at 7q33-q35 associated with autism spectrum disorders and primary amenorrhea Eur J Med Genet 2008 51 6 631 8 18675947
- Not checked yetcites [254] Poot M Beyer V Schwaab I Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder Neurogenetics 2010 11 1 81 9 19582487
- Not checked yetcites [255] O’Roak BJ Deriziotis P Lee C Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations Nat Genet 2011 43 6 585 9 21572417 PMC3115696
- Not checked yetcites [256] Alarcon M Abrahams BS Stone JL Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene Am J Hum Genet 2008 82 1 150 9 18179893 PMC2253955
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“genetic linkage and association studies have identified AKT as a candidate susceptibility gene related for SCZ [272, 273]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [272] Mathur A Law MH Megson IL Shaw DJ Wei J Genetic association of the AKT1 gene with schizophrenia in a British population Psychiatr Genet 2010 20 3 118 22 20421846
- Not checked yetcites [273] Karege F Perroud N Schurhoff F Association of AKT1 gene variants and protein expression in both schizophrenia and bipolar disorder Genes, brain, and behavior 2010 9 5 503 11 20214684
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Recent investigations have linked SCZ pathology to the PI3K-Akt-mTOR signaling cascade [268, 271].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [268] Gururajan A van den Buuse M Is the mTOR-signalling cascade disrupted in Schizophrenia? J Neurochem 2014 129 3 377 87 24266366
- Not checked yetcites [271] Kalkman HO The role of the phosphatidylinositide 3-kinase-protein kinase B pathway in schizophrenia Pharmacol Ther 2006 110 1 117 34 16434104
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“if protein production cannot be in tune with critical developmentally driven shifts, neuronal networks may be pathogenically imbalanced.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“other studies reported the reduction of several GABA subunits’ mRNA in the cortex but not in the cerebellum in FMR1-null mice [247, 248]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [247] D’Hulst C De Geest N Reeve SP Decreased expression of the GABAA receptor in fragile X syndrome Brain Res 2006 1121 1 238 45 17046729
- Not checked yetcites [248] D’Hulst C Heulens I Brouwer JR Expression of the GABAergic system in animal models for fragile X syndrome and fragile X associated tremor/ataxia syndrome (FXTAS) Brain Res 2009 1253 176 83 19070606
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“region-specific deletion of MECP2 can also recapitulate many of these behaviors.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [233] Chao HT Chen H Samaco RC Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes Nature 2010 468 7321 263 9 21068835 PMC3057962
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“genetic studies have consistently identified reoccurring CNVs mutual overlapping both disorders.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > CONVERGENT PATHWAYS OF ASD AND SCZ
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“FMR1-knockout mice, which exhibit autistic-like behaviors [245].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [245] Spencer CM Alekseyenko O Serysheva E Yuva-Paylor LA Paylor R Altered anxiety-related and social behaviors in the Fmr1 knockout mouse model of fragile X syndrome Genes, brain, and behavior 2005 4 7 420 30 16176388
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“FMRP is broadly expressed in GABAergic neuron populations [244]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [244] Olmos-Serrano JL Paluszkiewicz SM Martin BS Kaufmann WE Corbin JG Huntsman MM Defective GABAergic neurotransmission and pharmacological rescue of neuronal hyperexcitability in the amygdala in a mouse model of fragile X syndrome J Neurosci 2010 30 29 9929 38 20660275 PMC2948869
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Fragile X Syndrome (FXS) is a monogenetic neurodevelopmental disorder caused by an abnormal expansion of a CGG trinucleotide repeat within the promoter region of the gene FMR1, which prevents expression of the encoded protein FMRP [238].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [238] Wisniewski KE Segan SM Miezejeski CM Sersen EA Rudelli RD The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities Am J Med Genet 1991 38 2–3 476 80 2018089
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“25% exhibit epileptic symptoms [243]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [243] Coghlan S Horder J Inkster B Mendez MA Murphy DG Nutt DJ GABA system dysfunction in autism and related disorders: from synapse to symptoms Neurosci Biobehav Rev 2012 36 9 2044 55 22841562 PMC4477717
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“SCZ and ASD have been characterized as polygenic disorders, meaning multiple susceptibility genes may work together - possibly along different points of common pathways - to trigger disease onset [3].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > CONVERGENT PATHWAYS OF ASD AND SCZ
What the sources say
- Not checked yetcites [3] Harrison PJ Weinberger DR Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence Mol Psychiatry 2005 10 1 40 68 image 5 15263907
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“thus support the existence of shared biologic pathways between these two neurodevelopmental disorders.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > CONVERGENT PATHWAYS OF ASD AND SCZ
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Recent evidence suggests CNTNAP2 regulates neural networks through E/I balance.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the level of Akt-1 protein and its kinase activity decreased significantly both in white blood cells and in postmortem brain tissue of schizophrenic patients [274].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [274] Emamian ES Hall D Birnbaum MJ Karayiorgou M Gogos JA Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia Nat Genet 2004 36 2 131 7 14745448
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting enhanced signaling from the ErbB4 isoform CYT-1 lowers PI3K activity.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“NMDAR antagonist (e.g. PCP, MK-801, ketamine) administration in normal subjects produce metabolic, neurochemical, and cognitive deficits almost identical to SCZ patients [300]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [300] Morris BJ Cochran SM Pratt JA PCP: from pharmacology to modelling schizophrenia Curr Opin Pharmacol 2005 5 1 101 6 15661633
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“elevated NRG1-ErbB4 activity has been observed in SCZ postmortem brain tissue [283]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [283] Hahn CG Wang HY Cho DS Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia Nat Med 2006 12 7 824 8 16767099
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In the paper
“PTEN and TSC1 may have distinct mechanisms for E/I regulation [289].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [289] Weston MC Chen H Swann JW Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures Front Mol Neurosci 2014 7 1 24574959 PMC3922082
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In the paper
“mice with PTEN ablation from mature CA3 neurons, dentate granule cells, and layer III-V cortical neurons exhibit spontaneous seizures [213].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [213] Kwon CH Luikart BW Powell CM Pten regulates neuronal arborization and social interaction in mice Neuron 2006 50 3 377 88 16675393 PMC3902853
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In the paper
“disrupted network homeostasis via mTOR perturbation has been proposed as a pathophysiology mechanism contributing to autism spectrum disorders”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [286] Bourgeron T A synaptic trek to autism Curr Opin Neurobiol 2009 19 2 231 4 19545994
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these results suggest a specific requirement of depolarizing GABA signaling in DISC1-dependent regulation of Akt/mTOR signaling and dendritic growth during adult neurogenesis.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Pathological GABA signaling, therefore, may be indirectly responsible for the hallmark alterations in inhibitory circuits and behavior in SCZ via the DISC1-Akt-mTOR signaling pathway.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
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In the paper
“analysis from peripheral blood leucocytes from SCZ patients confirmed a 1.3 fold decrease in Akt levels [274].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [274] Emamian ES Hall D Birnbaum MJ Karayiorgou M Gogos JA Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia Nat Genet 2004 36 2 131 7 14745448
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In the paper
“NMDAR-associated proteins have key roles in the receptor’s trafficking, stability, subunit composition and function through post-translational modifications such as phosphorylation, ubiquitination, and palmitoylation.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
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In the paper
“adding evidence that enhanced NRG1-ErbB4 signaling may diminish PI3K-Akt signaling in SCZ.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“These findings suggest that in addition to its RNA-binding activity, FMRP also plays a role in the regulation of translation initiation and subsequent protein synthesis.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“dysbindin expression in the brain of schizophrenic patients is reduced [132, 133].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [132] Weickert CS Straub RE McClintock BW Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain Arch Gen Psychiatry 2004 61 6 544 55 15184234
- Not checked yetcites [133] Talbot K Eidem WL Tinsley CL Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia J Clin Invest 2004 113 9 1353 63 15124027 PMC398430
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In the paper
“NMDAR antagonist treatment specifically decreases GAD67 and parvalbumin in PV+ interneurons [301–303]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [301] Cochran SM Fujimura M Morris BJ Pratt JA Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain Synapse 2002 46 3 206 14 12325047
- Not checked yetcites [302] Kinney JW Davis CN Tabarean I Conti B Bartfai T Behrens MM A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons J Neurosci 2006 26 5 1604 15 16452684 PMC6675509
- Not checked yetcites [303] Behrens MM Ali SS Dao DN Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase Science 2007 318 5856 1645 7 18063801
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In the paper
“rapamycin treatment of DISC1 knockdown neurons prevented enhanced Akt phosphorylation and hypertrophic dendritic growth [261].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [261] Kim JY Duan X Liu CY DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212 Neuron 2009 63 6 761 73 19778506 PMC3075620
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting a relationship between mTOR hyperactivity and alterations of network circuits [270].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [270] Lasarge CL Danzer SC Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation Front Mol Neurosci 2014 7 18 24672426 PMC3953715
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“post-mortem studies reporting abnormalities in NMDAR density and subunit composition in SCZ patients [304, 305]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [304] Akbarian S Sucher NJ Bradley D Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics J Neurosci 1996 16 1 19 30 8613785 PMC6578738
- Not checked yetcites [305] Kristiansen LV Beneyto M Haroutunian V Meador-Woodruff JH Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia Mol Psychiatry 2006 11 8 737 47 05 16702973
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that dysbindin-1 deficits may contribute to the pathophysiology of SCZ by affecting neuronal viability of E/I circuits via regulation the PI3K/Akt signaling cascade.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“several lines of evidence suggest prominent ASD risk genes converge upon the mTOR signaling cascade to disrupt E/I balance via abnormal synaptic function owing to aberrations in synaptic protein translation.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“previous postmortem binding studies showing significant alterations in total NMDA receptor complexes only in particular regions of the Rett syndrome brain [336, 337].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [336] Blue ME Naidu S Johnston MV Development of amino acid receptors in frontal cortex from girls with Rett syndrome Ann Neurol 1999 45 4 541 5 10211484
- Not checked yetcites [337] Blue ME Naidu S Johnston MV Altered development of glutamate and GABA receptors in the basal ganglia of girls with Rett syndrome Exp Neurol 1999 156 2 345 52 10328941
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“MECP2-knockout (RTT) mice have abnormal NMDAR incorporation at the synapse.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“over-expression leads to clustering of synaptic NMDARs in excitatory synapses”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [330] Budreck EC Kwon OB Jung JH Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling Proceedings of the National Academy of Sciences of the United States of America 2013 110 2 725 30 23269831 PMC3545745
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“others show an over-representation of de novo mutations in glutamatergic postsynaptic proteins associated with NMDAR complexes in SCZ patients [68, 311]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [68] Fromer M Pocklington AJ Kavanagh DH De novo mutations in schizophrenia implicate synaptic networks Nature 2014 506 7487 179 84 24463507 PMC4237002
- Not checked yetcites [311] Kirov G Pocklington AJ Holmans P De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia Mol Psychiatry 2012 17 2 142 53 22083728 PMC3603134
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting NL1 recruits and retains NMDAR to postsynaptic sites [330].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [330] Budreck EC Kwon OB Jung JH Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling Proceedings of the National Academy of Sciences of the United States of America 2013 110 2 725 30 23269831 PMC3545745
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“NRG1-ErbB4 activity has been shown to down-regulate LTP via modifications in NMDAR surface trafficking”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [312] Gu Z Jiang Q Fu AK Ip NY Yan Z Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex J Neurosci 2005 25 20 4974 84 15901778 PMC6724849
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“one identified two de novo mutations in patients with sporadic SCZ in NR2A (GRIN2A) [310]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [310] Tarabeux J Kebir O Gauthier J Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia Transl Psychiatry 2011 1 e55 22833210 PMC3309470
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“SHANK3-knockdown mouse exhibited a decrease in NMDA/AMPA ratio in area CA1 of the hippocampus”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [329] Kouser M Speed HE Dewey CM Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission J Neurosci 2013 33 47 18448 68 24259569 PMC3834052
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“thereby defining Shank3’s role for NMDAR surface trafficking via the actin cytoskeleton mechanisms.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [327] Duffney LJ Wei J Cheng J Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism J Neurosci 2013 33 40 15767 78 24089484 PMC3787498
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“because the technique involved a whole-brain analysis, this does not provide detailed information to which specific brain region these alterations are taking place.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“NRG1 and ErbB4 accumulate at synapses in the adult brain”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“NL1 is selectively localized to excitatory synapses [182]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [182] Song JY Ichtchenko K Sudhof TC Brose N Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses Proceedings of the National Academy of Sciences of the United States of America 1999 96 3 1100 5 9927700 PMC15357
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“NMDAR subunits tend to be hotspots for de novo SCZ-associated mutation”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leading to the notion that NMDAR signaling could be a point of convergence for various SCZ-associated pathways.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“the repetitive behavior was ameliorated with NMDA co-partial agonist D-cycloserine”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [192] Blundell J Blaiss CA Etherton MR Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior J Neurosci 2010 30 6 2115 29 20147539 PMC2824441
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“several SCZ-specific polymorphisms in GRIN1 have been discovered [307, 308]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [307] Begni S Moraschi S Bignotti S Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia Biological psychiatry 2003 53 7 617 9 12679240
- Not checked yetcites [308] Zhao X Li H Shi Y Significant association between the genetic variations in the 5′ end of the N-methyl-D-aspartate receptor subunit gene GRIN1 and schizophrenia Biological psychiatry 2006 59 8 747 53 16476413
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“the extracellular NL1 cholinesterase domain, which differs between isoforms [154]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [154] Sudhof TC Neuroligins and neurexins link synaptic function to cognitive disease Nature 2008 455 7215 903 11 18923512 PMC2673233
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“both of which were rescued with exogenous Shank3 expression [328].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [328] Shcheglovitov A Shcheglovitova O Yazawa M SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients Nature 2013 503 7475 267 71 24132240 PMC5559273
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“interacts specifically with the NR1 subunit [330].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [330] Budreck EC Kwon OB Jung JH Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling Proceedings of the National Academy of Sciences of the United States of America 2013 110 2 725 30 23269831 PMC3545745
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“supporting the possible involvement of a malfunctioning NMDAR system in Rett syndrome pathophysiology.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NRG1’s regulation of NMDAR activity, therefore, may involve ErbB4-controlled postsynaptic mechanisms.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“FMRP normally binds to NMDAR subunits NR1, NR2A, and NR2B and components of the postsynaptic density, such as PSD-95 and CaMKIIα [338, 339].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [338] Zalfa F Eleuteri B Dickson KS A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability Nat Neurosci 2007 10 5 578 87 17417632 PMC2804293
- Not checked yetcites [339] Schutt J Falley K Richter D Kreienkamp HJ Kindler S Fragile X mental retardation protein regulates the levels of scaffold proteins and glutamate receptors in postsynaptic densities J Biol Chem 2009 284 38 25479 87 19640847 PMC2757949
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Other studies of RTT mice confirm there are regional differences within neural circuits in regards to connectivity [335]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [335] Shepherd GM Katz DM Synaptic microcircuit dysfunction in genetic models of neurodevelopmental disorders: focus on Mecp2 and Met Curr Opin Neurobiol 2011 21 6 827 33 21733672 PMC3199024
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“exhibited defunct context discrimination, a behavior reliant on intact NMDAR function in the DG [340].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [340] Eadie BD Cushman J Kannangara TS Fanselow MS Christie BR NMDA receptor hypofunction in the dentate gyrus and impaired context discrimination in adult Fmr1 knockout mice Hippocampus 2012 22 2 241 54 21049485
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“treatment with NMDAR co-agonists (glycine or D-serine) independently rescued synaptic impairments in this region [341].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [341] Bostrom CA Majaess NM Morch K White E Eadie BD Christie BR Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice Cereb Cortex 2015 25 1 271 9 23968838
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“differential manifestations of alterations in shared cellular substrates might underlie the phenotypic variability, which are then classified as distinct cognitive diseases.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > CONCLUSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: A significant symptom overlap exists between ASD and SCZ.
In the paper
“DG-specific deficits are also accompanied by a significant reduction in NR1, NR2A, and NR2B subunit levels”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [341] Bostrom CA Majaess NM Morch K White E Eadie BD Christie BR Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice Cereb Cortex 2015 25 1 271 9 23968838
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“exhibited defunct context discrimination, a behavior reliant on intact NMDAR function in the DG [340].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [340] Eadie BD Cushman J Kannangara TS Fanselow MS Christie BR NMDA receptor hypofunction in the dentate gyrus and impaired context discrimination in adult Fmr1 knockout mice Hippocampus 2012 22 2 241 54 21049485
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“the CA1 region of was not impaired in these mice [341].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [341] Bostrom CA Majaess NM Morch K White E Eadie BD Christie BR Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice Cereb Cortex 2015 25 1 271 9 23968838
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“FMRP differentially affects separate regions of the hippocampus”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [341] Bostrom CA Majaess NM Morch K White E Eadie BD Christie BR Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice Cereb Cortex 2015 25 1 271 9 23968838
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these historically distinct disorders might share overlapping pathogenic mechanisms.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > CONCLUSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: A significant symptom overlap exists between ASD and SCZ.
- It may state two separate claims as one. 117
- Probably not a substantial claim. 11
- The quote only partly states this claim. 1
None of the sources cited for this claim have been checked yet.
In the paper
“The behavioral symptoms of ASD and SCZ, however, are intriguingly similar; social interaction deficits, cognitive deficits, emotional processing problems, and executive functions dysfunction are all behavioral features commonly observed in both disorders [6, 7].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [6] Rapin I Tuchman RF Autism: definition, neurobiology, screening, diagnosis Pediatr Clin North Am 2008 55 5 1129 46 viii 18929056
- Not checked yetcites [7] Cheung C Yu K Fung G Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation PLoS One 2010 5 8 e12233 20805880 PMC2923607
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are two highly heritable spectrum disorders with complicated genetic etiologies but overlapping behavioral phenotypes [1].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [1] de Lacy N King BH Revisiting the relationship between autism and schizophrenia: toward an integrated neurobiology Annu Rev Clin Psychol 2013 9 555 87 23537488
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are cognitive disorders with complex genetic architectures but overlapping behavioral phenotypes, which suggests common pathway perturbations.”
- Also stated in: § INTRODUCTION · plain
“Autism Spectrum Disorders (ASD) and Schizophrenia (SCZ) are two highly heritable spectrum disorders with complicated genetic etiologies but overlapping behavioral phenotypes [1].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > Abstract
What the sources say
- Not checked yetcites [1] de Lacy N King BH Revisiting the relationship between autism and schizophrenia: toward an integrated neurobiology Annu Rev Clin Psychol 2013 9 555 87 23537488
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
- Also stated in: § INTRODUCTION · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Genetic linkage and genome-wide association studies (GWAS) have discovered a plethora of disease-associated genes, but few have been widely reproducible because each individual gene likely holds small influence on the overall disease pathogenesis [3, 4]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [3] Harrison PJ Weinberger DR Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence Mol Psychiatry 2005 10 1 40 68 image 5 15263907
- Not checked yetcites [4] Toro R Konyukh M Delorme R Key role for gene dosage and synaptic homeostasis in autism spectrum disorders Trends Genet 2010 26 8 363 72 20609491
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One emerging hypothesis maintains that alterations in the ratio of excitatory to inhibitory cortical activity (E/I imbalance) could explain the diseases’ similar social and cognitive deficits.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. The authors may not put it forward as true.
In the paper
“Gamma oscillations emerge from the synchronized firing of interconnected excitatory glutamatergic and primarily inhibitory fast-spiking GABAergic PV+ interneurons (Fig. 2), and its power (i.e. amplitude) is modulated by the E/I balance at distinct synaptic sites in the circuit and the intrinsic excitable properties of the neurons [46].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
What the sources say
- Not checked yetcites [46] Bartos M Vida I Jonas P Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks Nat Rev Neurosci 2007 8 1 45 56 17180162
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“NRG1 and ERBB4 are two of the most reproducible SCZ candidate genes [69–76].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [69] Stefansson H Sigurdsson E Steinthorsdottir V Neuregulin 1 and susceptibility to schizophrenia Am J Hum Genet 2002 71 4 877 92 12145742 PMC378543
- Not checked yetcites [70] Hall J Whalley HC Job DE A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms Nat Neurosci 2006 9 12 1477 8 17072305
- Not checked yetcites [71] Munafo MR Thiselton DL Clark TG Flint J Association of the NRG1 gene and schizophrenia: a meta-analysis Mol Psychiatry 2006 11 6 539 46 16520822
- Not checked yetcites [72] Munafo MR Attwood AS Flint J Neuregulin 1 genotype and schizophrenia Schizophr Bull 2008 34 1 9 12 18032396 PMC2632377
- Not checked yetcites [73] Silberberg G Darvasi A Pinkas-Kramarski R Navon R The involvement of ErbB4 with schizophrenia: association and expression studies Am J Med Genet B Neuropsychiatr Genet 2006 141B 2 142 8 16402353
- Not checked yetcites [74] Law AJ Kleinman JE Weinberger DR Weickert CS Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia Hum Mol Genet 2007 16 2 129 41 17164265
- Not checked yetcites [75] Nicodemus KK Law AJ Radulescu E Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls Arch Gen Psychiatry 2010 67 10 991 1001 20921115 PMC4291187
- Not checked yetcites [76] Tan W Dean M Law AJ Molecular cloning and characterization of the human ErbB4 gene: identification of novel splice isoforms in the developing and adult brain PLoS One 2010 5 9 e12924 20886074 PMC2944867
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Turrigiano et al. [39] discovered chronic activity blockade with tetrodotoxin (TTX) and bicuculline increased and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSC) respectively in cultured neurons, while drug washout restored firing rates to control levels.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
What the sources say
- Not checked yetcites [39] Turrigiano GG Leslie KR Desai NS Rutherford LC Nelson SB Activity-dependent scaling of quantal amplitude in neocortical neurons Nature 1998 391 6670 892 6 9495341
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DISC1 was originally identified through a disruption in its open reading frame in a large Scottish pedigree [90] and later verified to be a legitimate SCZ risk gene through polymorphisms and frame shift mutations in other SCZ-afflicted lineages [91].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [90] Millar JK Wilson-Annan JC Anderson S Disruption of two novel genes by a translocation co-segregating with schizophrenia Hum Mol Genet 2000 9 9 1415 23 10814723
- Not checked yetcites [91] Schumacher J Laje G Abou Jamra R The DISC locus and schizophrenia: evidence from an association study in a central European sample and from a meta-analysis across different European populations Hum Mol Genet 2009 18 14 2719 27 19414483 PMC2701338
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“While glutamatergic synapses are found almost exclusively on dendritic spines [2], GABAergic synapses are localized along the dendritic shaft, somata, and axon initial segments [15].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Synapses and Dendrite Arborization
What the sources say
- Not checked yetcites [2] Penzes P Cahill ME Jones KA VanLeeuwen JE Woolfrey KM Dendritic spine pathology in neuropsychiatric disorders Nat Neurosci 2011 14 3 285 93 21346746 PMC3530413
- Not checked yetcites [15] Fritschy JM Brunig I Formation and plasticity of GABAergic synapses: physiological mechanisms and pathophysiological implications Pharmacol Ther 2003 98 3 299 323 12782242
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Long-term NRG1 treatment increases pyramidal neuronal spine density and the preponderance of spines with mature phenotypes [84]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [84] Barros CS Calabrese B Chamero P Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system Proceedings of the National Academy of Sciences of the United States of America 2009 106 11 4507 12 19240213 PMC2657442
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Perplexingly, ErbB4 is found at much higher levels in interneuron excitatory synapses - especially belonging to the PV+ interneuron subtype - and a recent study used in vivo techniques to directly demonstrate ErbB4’s specificity in controlling cortical GABAergic circuit development [87].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [87] Fazzari P Paternain AV Valiente M Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling Nature 2010 464 7293 1376 80 20393464
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For the purposes of this review, we will focus largely on PV+ interneurons because they play an essential role in proper cognitive function and are noticeably afflicted in ASD and SCZ patients.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > GABAergic Neurons
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, circuits tend to be malleable but vulnerable during postnatal development; notably, several neurodevelopmental disorders, such as ASD and SCZ, manifest during this plasticity period [49, 50].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
What the sources say
- Not checked yetcites [49] Zoghbi HY Postnatal neurodevelopmental disorders: meeting at the synapse? Science 2003 302 5646 826 30 14593168
- Not checked yetcites [50] Fatemi SH Folsom TD The neurodevelopmental hypothesis of schizophrenia, revisited Schizophr Bull 2009 35 3 528 48 19223657 PMC2669580
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, ErbB4 over-expression increases spine density, area, and excitatory synaptic transmission while ErbB4 knockdown reduces spine density and size [86].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [86] Li B Woo RS Mei L Malinow R The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity Neuron 2007 54 4 583 97 17521571 PMC2031848
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Such imbalances may arise from problems in initial neural circuit formation or maintenance, as many of the genes derived from linkage and association studies code for proteins involved with these processes [4, 11].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > INTRODUCTION
What the sources say
- Not checked yetcites [4] Toro R Konyukh M Delorme R Key role for gene dosage and synaptic homeostasis in autism spectrum disorders Trends Genet 2010 26 8 363 72 20609491
- Not checked yetcites [11] Penzes P Buonanno A Passafaro M Sala C Sweet RA Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders J Neurochem 2013 126 2 165 82 23574039 PMC3700683
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, multiple postmortem studies have reproducibly found lower levels of parvalbumin mRNA and GAD67, the principal synthesizing enzyme for GABA, in DLPFC PV+ neurons, but found the absolute number of PV+ cells unchanged, suggesting a functional rather than a numerical deficit [64, 65].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF SCHIZOPHRENIA
What the sources say
- Not checked yetcites [64] Lewis DA Hashimoto T Volk DW Cortical inhibitory neurons and schizophrenia Nat Rev Neurosci 2005 6 4 312 24 15803162
- Not checked yetcites [65] Hashimoto T Volk DW Eggan SM Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia J Neurosci 2003 23 15 6315 26 12867516 PMC6740534
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, mice lacking ErbB4 in the CNS show reduced spine density in both the hippocampus and cortex and exhibit schizophrenia-related behavioral phenotypes [84].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [84] Barros CS Calabrese B Chamero P Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system Proceedings of the National Academy of Sciences of the United States of America 2009 106 11 4507 12 19240213 PMC2657442
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Behavioral phenotypes in rodent models described as schizophrenia-like or autism-like correspond to the human disorders.
In the paper
“Bateup et al. [47] showed loss of TSC1, a gene encoding a regulator of mTOR signaling (see mTOR and ASD) in hippocampal cultures resulted in a primary decrease of inhibitory synaptic transmission, followed closely by a futile secondary homeostatic response, and concluded with an overall increase in network hyperexcitability.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > THE PHYSIOLOGY OF E/I BALANCE > Excitatory/Inhibitory Balance
What the sources say
- Not checked yetcites [47] Bateup HS Johnson CA Denefrio CL Saulnier JL Kornacker K Sabatini BL Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis Neuron 2013 78 3 510 22 23664616 PMC3690324
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For instance, a SCZ-associated SNP in the transmembrane domain of NRG1 leads to disruptions in gamma-secretase dependent cleavage of the protein, which in turn reduces NRG1-mediated intracellular signaling and abolishes NRG1-regulated growth of pyramidal dendrites [88].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > Neuregulin1/ErbB4
What the sources say
- Not checked yetcites [88] Chen Y Hancock ML Role LW Talmage DA Intramembranous valine linked to schizophrenia is required for neuregulin 1 regulation of the morphological development of cortical neurons J Neurosci 2010 30 27 9199 208 20610754 PMC2919805
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“DTNBP1-knockout mice have reductions in the excitability of cortical and striatal PV+ interneurons, which in turn lead to hyperexcitable pyramidal cells [134].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > DISC1/Dysbindin
What the sources say
- Not checked yetcites [134] Ji Y Yang F Papaleo F Role of dysbindin in dopamine receptor trafficking and cortical GABA function Proceedings of the National Academy of Sciences of the United States of America 2009 106 46 19593 8 19887632 PMC2780743
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similarly, mice harboring full or PV+ targeted ablation of ErbB4 exhibit reductions in kainate induced gamma oscillation power and exhibit severe SCZ-like behaviors [123–125].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [123] Fisahn A Neddens J Yan L Buonanno A Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia Cereb Cortex 2009 19 3 612 8 18632742 PMC2638818
- Not checked yetcites [124] Wen L Lu YS Zhu XH Neuregulin 1 regulates pyramidal neuron activity via ErbB4 in parvalbumin-positive interneurons Proceedings of the National Academy of Sciences of the United States of America 2010 107 3 1211 6 20080551 PMC2824309
- Not checked yetcites [125] Shamir A Kwon OB Karavanova I The importance of the NRG-1/ErbB4 pathway for synaptic plasticity and behaviors associated with psychiatric disorders J Neurosci 2012 32 9 2988 97 22378872 PMC3302154
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Behavioral phenotypes in rodent models described as schizophrenia-like or autism-like correspond to the human disorders.
None of the sources cited for this claim have been checked yet.
In the paper
“DISC1 is a scaffold protein intimately involved with hippocampal development [98–100] and is found abundantly at the spines [101], where it facilitates the formation of protein complexes with its coiled-coil rich C-terminal domain.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [98] Austin CP Ky B Ma L Morris JA Shughrue PJ Expression of Disrupted-In-Schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development Neuroscience 2004 124 1 3 10 14960334
- Not checked yetcites [99] Enomoto A Asai N Namba T Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus Neuron 2009 63 6 774 87 19778507
- Not checked yetcites [100] Meyer KD Morris JA Disc1 regulates granule cell migration in the developing hippocampus Hum Mol Genet 2009 18 17 3286 97 19502360 PMC2722990
- Not checked yetcites [101] Kirkpatrick B Xu L Cascella N Ozeki Y Sawa A Roberts RC DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex J Comp Neurol 2006 497 3 436 50 16736468
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“2) ErbB4 cell-autonomously regulates the formation of excitatory synapses on these inhibitory subtypes and the formation of inhibitory synapses from PV+ subtypes onto neighboring pyramidal cells.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [87] Fazzari P Paternain AV Valiente M Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling Nature 2010 464 7293 1376 80 20393464
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, it was demonstrated that perfusion of hippocampal slices with small doses of NRG1 led to increases in kainate-induced gamma oscillations. This effect was ErbB4-dependent, as it was blocked with an ErbB4 antagonist and was absent in ERBB4-knockout mice [123].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [123] Fisahn A Neddens J Yan L Buonanno A Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia Cereb Cortex 2009 19 3 612 8 18632742 PMC2638818
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“More specifically, ErbB4 is expressed in nearly all PV+ interneurons in the neocortex [120] and over half in the hippocampus [123].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [120] Neddens J Buonanno A Expression of the neuregulin receptor ErbB4 in the brain of the rhesus monkey (Macaca mulatta) PLoS One 2011 6 11 e27337 22087295 PMC3210802
- Not checked yetcites [123] Fisahn A Neddens J Yan L Buonanno A Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia Cereb Cortex 2009 19 3 612 8 18632742 PMC2638818
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Synchronization of cortical and hippocampal neural networks at gamma frequencies (30–80) Hz is important for proper cognition, memory, and learning [108], but are perturbed in schizophrenic patients [58, 109, 110].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT
What the sources say
- Not checked yetcites [108] Engel AK Singer W Temporal binding and the neural correlates of sensory awareness Trends Cogn Sci 2001 5 1 16 25 11164732
- Not checked yetcites [58] Gonzalez-Burgos G Lewis DA GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia Schizophr Bull 2008 34 5 944 61 18586694 PMC2518635
- Not checked yetcites [109] Herrmann CS Demiralp T Human EEG gamma oscillations in neuropsychiatric disorders Clin Neurophysiol 2005 116 12 2719 33 16253555
- Not checked yetcites [110] Spencer KM The functional consequences of cortical circuit abnormalities on gamma oscillations in schizophrenia: insights from computational modeling Front Hum Neurosci 2009 3 33 19876408 PMC2769552
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In SCZ patients carrying high risk DISC1 SNPs, DISC1-interacting protein expression levels, but not DISC1 mRNA levels, are drastically reduced [102], suggesting that DISC1 function might be affected in SCZ.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [102] Lipska BK Peters T Hyde TM Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs Hum Mol Genet 2006 15 8 1245 58 16510495
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Early brain overgrowth and neuronal hyperexcitability are two well-established phenotypes in ASD [135, 136].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [135] Parellada M Penzol MJ Pina L The neurobiology of autism spectrum disorders Eur Psychiatry 2014 29 1 11 9 24275633
- Not checked yetcites [136] Rubenstein JL Merzenich MM Model of autism: increased ratio of excitation/inhibition in key neural systems Genes, brain, and behavior 2003 2 5 255 67 PMC6748642 14606691
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recently, the Rac-GEF Kalirin-7 has been identified as a DISC1 interacting partner and has been shown to directly regulate DISC1’s effects on spine morphology through Rac1 [103].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [103] Hayashi-Takagi A Takaki M Graziane N Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1 Nat Neurosci 2010 13 3 327 32 20139976 PMC2846623
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Finally, a KALRN-knockout mouse shows severe reductions in spine density in the frontal cortex and schizophrenic-like behaviors during adolescent years [105].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > DISC1
What the sources say
- Not checked yetcites [105] Cahill ME Xie Z Day M Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes Proceedings of the National Academy of Sciences of the United States of America 2009 106 31 13058 63 19625617 PMC2722269
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Behavioral phenotypes in rodent models described as schizophrenia-like or autism-like correspond to the human disorders.
In the paper
“The 22q11 microdeletion syndrome is the most common copy number variant (CNV) associated with SCZ and accounts for up to 1–2% of the cases [106].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GLUTAMATERGIC CIRCUIT > 22q11 microdeletion
What the sources say
- Not checked yetcites [106] Stark KL Xu B Bagchi A Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model Nat Genet 2008 40 6 751 60 18469815
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For instance, the fragile X brain is characterized by macrocephaly, elevated spine density and elongated, tortuous spine morphologies [139].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [139] Irwin SA Patel B Idupulapati M Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination Am J Med Genet 2001 98 2 161 7 11223852
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“1) ErbB4 is expressed both in the axon terminals and post-synaptic excitatory synapses of PV+ chandelier and basket cells, but not in pyramidal cells.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > ErbB4
What the sources say
- Not checked yetcites [87] Fazzari P Paternain AV Valiente M Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling Nature 2010 464 7293 1376 80 20393464
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“while 30% struggle with epilepsy [138].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
What the sources say
- Not checked yetcites [138] Tuchman R Rapin I Epilepsy in autism Lancet Neurol 2002 1 6 352 8 12849396
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For instance, mutant mice that overexpress a dominant negative form of DISC1 have reduced PV+ immunoreactivity in the prefrontal cortex, suggesting DISC1 is necessary for proper functioning of GABAergic cortical interneurons [129].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > SCHIZOPHRENIA AT THE GABAergic CIRCUIT > DISC1/Dysbindin
What the sources say
- Not checked yetcites [129] Hikida T Jaaro-Peled H Seshadri S Dominant-negative DISC1 transgenic mice display schizophrenia-associated phenotypes detected by measures translatable to humans Proceedings of the National Academy of Sciences of the United States of America 2007 104 36 14501 6 17675407 PMC1964873
hedgeddirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Knockout mice lacking all three α-Nrxns or NLs 1–3 show little change in total number of synapses but exhibit severe synaptic transmission phenotypes [159, 160], thereby implicating Nrxn-NLs in synaptic function, but not formation, in vivo.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [159] Missler M Zhang W Rohlmann A Alpha-neurexins couple Ca2+ channels to synaptic vesicle exocytosis Nature 2003 423 6943 939 48 12827191
- Not checked yetcites [160] Varoqueaux F Aramuni G Rawson RL Neuroligins determine synapse maturation and function Neuron 2006 51 6 741 54 16982420
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“NLGN3-knockout mice have reduced ultrasound vocalization, deficits in social novelty preference, and brain volume reduction”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [194] Radyushkin K Hammerschmidt K Boretius S Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit Genes, brain, and behavior 2009 8 4 416 25 19243448
- Not checked yetcites [195] Jamain S Radyushkin K Hammerschmidt K Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism Proceedings of the National Academy of Sciences of the United States of America 2008 105 5 1710 5 18227507 PMC2234209
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, neurexins and neuroligins may contribute to ASD pathogenesis through its control of synaptic function; deregulation may result in neurodevelopmental imbalances of synaptic transmission and may progress to behavioral changes.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Neuroligins (NL1-4) are a group of postsynaptic cell adhesion proteins [154] which interact with presynaptic Neurexins (Nrxns 1–3) to form trans-synaptic adhesions [155–158].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [154] Sudhof TC Neuroligins and neurexins link synaptic function to cognitive disease Nature 2008 455 7215 903 11 18923512 PMC2673233
- Not checked yetcites [155] Ichtchenko K Hata Y Nguyen T Neuroligin 1: a splice site-specific ligand for beta-neurexins Cell 1995 81 3 435 43 7736595
- Not checked yetcites [156] Ichtchenko K Nguyen T Sudhof TC Structures, alternative splicing, and neurexin binding of multiple neuroligins J Biol Chem 1996 271 5 2676 82 8576240
- Not checked yetcites [157] Comoletti D Flynn RE Boucard AA Gene selection, alternative splicing, and post-translational processing regulate neuroligin selectivity for beta-neurexins Biochemistry 2006 45 42 12816 27 17042500
- Not checked yetcites [158] Chih B Gollan L Scheiffele P Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex Neuron 2006 51 2 171 8 16846852
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Kwon et al. [163] showed that synapse formation in vivo was specifically dependent on transcellular differences in NL1 levels between neighboring neurons, suggesting that nascent neurons compete for limited presynaptic neurexin ligands, with cells expressing more NL1 forming synapses more readily.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [163] Kwon HB Kozorovitskiy Y Oh WJ Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number Nat Neurosci 2012 15 12 1667 74 23143522 PMC3536444
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both groups have been genetically linked with ASD: point mutants in NLGN3, NLGN4, or NRXN1 [165–169] truncations of NLGN4 or NRXN1 [170–172], chromosomal rearrangements of regions harboring NRXN1, NLGN1, or NLGN2 [173, 174], and a promoter mutation in NLGN4 [175] have been identified.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [165] Comoletti D De Jaco A Jennings LL The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing J Neurosci 2004 24 20 4889 93 15152050 PMC6729460
- Not checked yetcites [166] Etherton MR Tabuchi K Sharma M Ko J Sudhof TC An autism-associated point mutation in the neuroligin cytoplasmic tail selectively impairs AMPA receptor-mediated synaptic transmission in hippocampus EMBO J 2011 30 14 2908 19 21642956 PMC3160244
- Not checked yetcites [167] Zhang C Milunsky JM Newton S A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export J Neurosci 2009 29 35 10843 54 19726642 PMC2777970
- Not checked yetcites [168] Feng J Schroer R Yan J High frequency of neurexin 1beta signal peptide structural variants in patients with autism Neurosci Lett 2006 409 1 10 3 17034946
- Not checked yetcites [169] Jamain S Quach H Betancur C Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism Nat Genet 2003 34 1 27 9 12669065 PMC1925054
- Not checked yetcites [170] Lawson-Yuen A Saldivar JS Sommer S Picker J Familial deletion within NLGN4 associated with autism and Tourette syndrome Eur J Hum Genet 2008 16 5 614 8 18231125
- Not checked yetcites [171] Zahir FR Baross A Delaney AD A patient with vertebral, cognitive and behavioural abnormalities and a de novo deletion of NRXN1alpha J Med Genet 2008 45 4 239 43 18057082
- Not checked yetcites [172] Gauthier J Siddiqui TJ Huashan P Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia Hum Genet 2011 130 4 563 73 21424692 PMC3204930
- Not checked yetcites [173] Konstantareas MM Homatidis S Chromosomal abnormalities in a series of children with autistic disorder J Autism Dev Disord 1999 29 4 275 85 10478727
- Not checked yetcites [174] Kim HG Kishikawa S Higgins AW Disruption of neurexin 1 associated with autism spectrum disorder Am J Hum Genet 2008 82 1 199 207 18179900 PMC2253961
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“All three members of the Shank family of have been linked with ASD susceptibility: a large number of de novo mutations in SHANK3 [197–199], in SHANK2 [200], and in SHANK1 [201] have been identified in individuals with ASD.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
What the sources say
- Not checked yetcites [197] Durand CM Betancur C Boeckers TM Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders Nat Genet 2007 39 1 25 7 17173049 PMC2082049
- Not checked yetcites [198] Moessner R Marshall CR Sutcliffe JS Contribution of SHANK3 mutations to autism spectrum disorder Am J Hum Genet 2007 81 6 1289 97 17999366 PMC2276348
- Not checked yetcites [199] Gauthier J Spiegelman D Piton A Novel de novo SHANK3 mutation in autistic patients Am J Med Genet B Neuropsychiatr Genet 2009 150B 3 421 4 18615476
- Not checked yetcites [200] Berkel S Marshall CR Weiss B Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation Nat Genet 2010 42 6 489 91 20473310
- Not checked yetcites [201] Sato D Lionel AC Leblond CS SHANK1 Deletions in Males with Autism Spectrum Disorder Am J Hum Genet 2012 90 5 879 87 22503632 PMC3376495
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest heterogenous changes in glutamatergic and GABAergic systems in the ASD brain can converge upon an overall increased ratio of excitation/inhibition, which can manifest in epileptic symptoms, macroscopic changes in brain volume, and behavioral alterations.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NEUROPATHOLOGICAL FEATURES OF ASD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“α-NRXN1-knockout mice have hippocampal E/I imbalance due to decreased spontaneous excitatory post-synaptic currents and decreased prepulse inhibitions”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [181] Etherton MR Blaiss CA Powell CM Sudhof TC Mouse neurexin-1alpha deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments Proceedings of the National Academy of Sciences of the United States of America 2009 106 42 17998 8003 19822762 PMC2764944
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“SHANK1-knockout mice have small dendritic spines, weakened synaptic transmission [203], and defects in social communication [204].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
What the sources say
- Not checked yetcites [203] Hung AY Futai K Sala C Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1 J Neurosci 2008 28 7 1697 708 18272690 PMC2633411
- Not checked yetcites [204] Wohr M Roullet FI Hung AY Sheng M Crawley JN Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior PLoS One 2011 6 6 e20631 21695253 PMC3111434
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these studies demonstrate that the SHANK genes cause alterations in excitatory synaptic morphology and signaling, as well as changes in behavior characteristics, suggesting they are good animal models for the study of synaptic pathology in ASD.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Rett Syndrome is a neurodevelopmental disorder that presents at around 6–18 months with autistic-like deficiencies in speech, social and motor skills - particularly repetitive movements - which results from the functional loss of one copy of the MECP2 gene [227, 228].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [227] Chahrour M Zoghbi HY The story of Rett syndrome: from clinic to neurobiology Neuron 2007 56 3 422 37 17988628
- Not checked yetcites [228] Guy J Cheval H Selfridge J Bird A The role of MeCP2 in the brain Annu Rev Cell Dev Biol 2011 27 631 52 21721946
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“each of these proteins regulates synaptic structure [213–215].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [213] Kwon CH Luikart BW Powell CM Pten regulates neuronal arborization and social interaction in mice Neuron 2006 50 3 377 88 16675393 PMC3902853
- Not checked yetcites [214] Tavazoie SF Alvarez VA Ridenour DA Kwiatkowski DJ Sabatini BL Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2 Nat Neurosci 2005 8 12 1727 34 16286931
- Not checked yetcites [215] Fraser MM Bayazitov IT Zakharenko SS Baker SJ Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities Neuroscience 2008 151 2 476 88 18082964 PMC2278004
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the SHANK2-knockout mice, like their SHANK3-knockout counterparts, show abnormalities in behavior tests, impairment in social activities, hyperactivity, and defects in synaptic transmission [208, 209].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
What the sources say
- Not checked yetcites [208] Schmeisser MJ Ey E Wegener S Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2 Nature 2012 486 7402 256 60 22699619
- Not checked yetcites [209] Won H Lee HR Gee HY Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function Nature 2012 486 7402 261 5 22699620
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“while NL3 is predominantly localized to excitatory synapses [184], it is also found to a lesser extent in GABAergic synapses [183].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [184] Graf ER Zhang X Jin SX Linhoff MW Craig AM Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins Cell 2004 119 7 1013 26 15620359 PMC2826211
- Not checked yetcites [183] Budreck EC Scheiffele P Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses Eur J Neurosci 2007 26 7 1738 48 17897391
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The behavioral defects of SHANK3 mutant mice correlate with impaired basal synaptic transmission in CA3-CA1 connections, reduced GluR1 clusters and protein levels in the hippocampus, and major changes in striatal and corticostriatal synapses [205–207].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
What the sources say
- Not checked yetcites [205] Bozdagi O Sakurai T Papapetrou D Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication Mol Autism 2010 1 1 15 21167025 PMC3019144
- Not checked yetcites [206] Peca J Feliciano C Ting JT Shank3 mutant mice display autistic-like behaviours and striatal dysfunction Nature 2011 472 7344 437 42 21423165 PMC3090611
- Not checked yetcites [207] Wang X McCoy PA Rodriguiz RM Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3 Hum Mol Genet 2011 20 15 3093 108 21558424 PMC3131048
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mice with heterozygous or homozygous disruption of SHANK3 have self-injurious repetitive grooming, deficits in social interaction, alterations in learning and memory formation, and defects in synaptic transmission [205–207].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > SHANK Family
What the sources say
- Not checked yetcites [205] Bozdagi O Sakurai T Papapetrou D Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication Mol Autism 2010 1 1 15 21167025 PMC3019144
- Not checked yetcites [206] Peca J Feliciano C Ting JT Shank3 mutant mice display autistic-like behaviours and striatal dysfunction Nature 2011 472 7344 437 42 21423165 PMC3090611
- Not checked yetcites [207] Wang X McCoy PA Rodriguiz RM Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3 Hum Mol Genet 2011 20 15 3093 108 21558424 PMC3131048
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A knock-in mouse harboring an autism-associated mutation in a conserved amino acid residue (R451C) of NLGN3 was found have increased inhibitory transmission but no changes in excitatory transmission in the somatosensory cortex [225].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [225] Tabuchi K Blundell J Etherton MR A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice Science 2007 318 5847 71 6 17823315 PMC3235367
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“MeCP2 is a transcriptional regulator which is highly expressed in GABAergic neurons in the brain [229]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [229] Akbarian S Chen RZ Gribnau J Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex Neurobiol Dis 2001 8 5 784 91 11592848
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“these mice had stereotypied behavior and impaired social interactions [224].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [224] Hines RM Wu L Hines DJ Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression J Neurosci 2008 28 24 6055 67 18550748 PMC6670530
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“even slight alterations to NL2 can significantly alter E/I balance and result in particular behavioral deficits.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“in vitro NL2 over-expression or knockdown specifically enhanced or decreased inhibitory circuit transmission respectively [188]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [188] Chubykin AA Atasoy D Etherton MR Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2 Neuron 2007 54 6 919 31 17582332 PMC3738748
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these studies provide evidence that both reduced and enhanced expression of ASD genes such as NLs can intimately affect the balance between excitatory and inhibitory transmission, and hence provides strong evidence that a change in the E/I balance contributes to the pathogenesis of ASDs.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PTEN deficiency results in hypertrophy of dendritic arbors and increased spine density [213, 216]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [213] Kwon CH Luikart BW Powell CM Pten regulates neuronal arborization and social interaction in mice Neuron 2006 50 3 377 88 16675393 PMC3902853
- Not checked yetcites [216] Pun RY Rolle IJ Lasarge CL Excessive activation of mTOR in postnatally generated granule cells is sufficient to cause epilepsy Neuron 2012 75 6 1022 34 22998871 PMC3474536
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Hoon et al. [226] showed NL4 was endogenously localized to inhibitory glycinergic synapses in the retina and other areas of the CNS, associates with gephyrin but not PSD-95 in vivo, and is important for glycinergic-dependent inhibitory transmission in the retina.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [226] Hoon M Soykan T Falkenburger B Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina Proceedings of the National Academy of Sciences of the United States of America 2011 108 7 3053 8 21282647 PMC3041141
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“loss of FMRP causes an upregulation in global dendritic translation rates that may contribute to the elevated spine density observed in the brains of affected individuals [217].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GLUTAMATERGIC CIRCUIT > Syndromic Autisms
What the sources say
- Not checked yetcites [217] Bagni C Greenough WT From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome Nat Rev Neurosci 2005 6 5 376 87 15861180
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a transgenic mouse harboring an extra copy of the NLGN2 gene resulted in increased size of inhibitory synapses and a subsequent reduction in the E/I ratio.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [224] Hines RM Wu L Hines DJ Synaptic imbalance, stereotypies, and impaired social interactions in mice with altered neuroligin 2 expression J Neurosci 2008 28 24 6055 67 18550748 PMC6670530
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This interaction provides a physical link between pre- and post-synaptic membranes [158], regulates pre-synaptic neurotransmitter release, and post-synaptically recruits gephyrin which scaffolds GABAA receptors in precise locations [223].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > Neurexins/Neuroligins
What the sources say
- Not checked yetcites [158] Chih B Gollan L Scheiffele P Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex Neuron 2006 51 2 171 8 16846852
- Not checked yetcites [223] Huang ZJ Scheiffele P GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development Curr Opin Neurobiol 2008 18 1 77 83 18513949 PMC3988756
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CNTNAP2-knockout mice have reduced numbers of PV+ GABAergic interneurons, as well as neuronal synchrony defects, epileptic seizures, and altered social behavior [258].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
What the sources say
- Not checked yetcites [258] Penagarikano O Abrahams BS Herman EI Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits Cell 2011 147 1 235 46 21962519 PMC3390029
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CNTNAP2 loss may lead to impairments in connectivity and reductions in the interneuron population, particularly the PV+ subtype, resulting in a hyper-excitable network that promotes downstream epileptic symptoms and behavioral abnormalities.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“thus implicating FMR1 both as an autism susceptibility gene and a regulator of cortical inhibitory function.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Active Akt phosphorylates TSC1/TSC2 to disinhibit Rheb, leading to protein translation through mTOR’s (as a member of mTORC1) phosphorylation of S6 kinase (S6K) and eukaryotic initiation factor (eIF-4B) [268].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
What the sources say
- Not checked yetcites [268] Gururajan A van den Buuse M Is the mTOR-signalling cascade disrupted in Schizophrenia? J Neurochem 2014 129 3 377 87 24266366
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these results suggest that MeCP2 function may be more crucial in some inhibitory circuits than others and that behavioral symptoms may be the downstream result of region-specific MeCP2-associated defects in GABAergic neurons.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“knockout mice have significant reductions and drastic lamina redistributions of PV+ interneurons in the neocortex, but not hippocampus”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
What the sources say
- Not checked yetcites [246] Selby L Zhang C Sun QQ Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein Neurosci Lett 2007 412 3 227 32 17197085 PMC1839948
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CNTNAP2 knockdown led to decreases in dendrite arborization and impaired synaptic transmission in mouse cortical neurons [257].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
What the sources say
- Not checked yetcites [257] Anderson GR Galfin T Xu W Aoto J Malenka RC Sudhof TC Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development Proceedings of the National Academy of Sciences of the United States of America 2012 109 44 18120 5 23074245 PMC3497786
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“mice with specific deletion of MECP2 from forebrain GABAergic-interneurons exhibit repetitive behaviors, increased sociability, cognitive deficits, impaired motor coordination and neuronal hyperexcitability [233].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [233] Chao HT Chen H Samaco RC Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes Nature 2010 468 7321 263 9 21068835 PMC3057962
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Phosphorylation of TSC1/TSC2 dissociates with and thereby activates Rheb.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“mTOR is controlled by the tuberous sclerosis complex (TSC1/TSC2), a heteromer which binds and constitutively inhibits the GTPase Ras-homolog enriched in brain (Rheb), a direct activator of mTOR.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CNTNAP2 is expressed at the ganglionic eminences during development [258] and interacts to TAG-1 [259], a protein involved in interneuron migration [260].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
What the sources say
- Not checked yetcites [258] Penagarikano O Abrahams BS Herman EI Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits Cell 2011 147 1 235 46 21962519 PMC3390029
- Not checked yetcites [259] Traka M Goutebroze L Denisenko N Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers J Cell Biol 2003 162 6 1161 72 12975355 PMC2172849
- Not checked yetcites [260] Denaxa M Chan CH Schachner M Parnavelas JG Karagogeos D The adhesion molecule TAG-1 mediates the migration of cortical interneurons from the ganglionic eminence along the corticofugal fiber system Development 2001 128 22 4635 44 11714688
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Activated PI3K promotes plasma membrane translocation and subsequent activation of Protein Kinase B (Akt) via production of phosphatidylinositol (3,4,5)- triphosphate (PIP3); meanwhile, PTEN opposes PI3K by depleting PIP3.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“brain-derived neurotrophic factor (BDNF), which regulates development and maturation of inhibitory circuits in the brain, is a MeCP2 target [237].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > MeCP2
What the sources say
- Not checked yetcites [237] Martinowich K Hattori D Wu H DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation Science 2003 302 5646 890 3 14593184
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“FXS mice are good animal models analyze how FMRP links region-specific GABA dysregulation to autistic symptoms; however, caution must be taken as that FXS is not a “pure” autism and thus cannot entirely be relied upon to understand the latter’s complex pathophysiology.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > FMRP
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Contactin-associated protein-like 2 (CNTNAP2) is a neurexin cell-adhesion molecule that is highly expressed throughout the central nervous system, with highest expression in the frontal and anterior lobes, striatum and dorsal thalamus [256]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > ASD AT THE GABAergic CIRCUIT > CNTNAP2
What the sources say
- Not checked yetcites [256] Alarcon M Abrahams BS Stone JL Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene Am J Hum Genet 2008 82 1 150 9 18179893 PMC2253955
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“binding of various extracellular factors (mitogens, trophic factors, and glutamate) to respective receptors lead to the activation of phosphatidylinositol 3-kinase (PI3K) at the plasma membrane.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this discovery may have joined two previously disparate pathways.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NMDAR dysfunction could be a convergence point in ASD and SCZ pathophysiology and may be responsible for disease progression in both disorders.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DISC1 knockdown of adult-born neurons in the dentate gyrus led to acceleration of dendrite development, network hyperexcitability, and an increase in phosphorylated Akt.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Lymphoblast lines from schizophrenic patients have upregulated expression of the ErbB4 receptor isoform CYT-1, which contains a PI3K-binding site and triggers activation of the PI3K pathway [280, 281].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [280] Junttila TT Sundvall M Maatta JA Elenius K Erbb4 and its isoforms: selective regulation of growth factor responses by naturally occurring receptor variants Trends Cardiovasc Med 2000 10 7 304 10 11343971
- Not checked yetcites [281] Law AJ Wang Y Sei Y Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110delta inhibition as a potential therapeutic strategy Proceedings of the National Academy of Sciences of the United States of America 2012 109 30 12165 70 22689948 PMC3409795
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“mTOR regulates a variety of neuronal functions, including cell proliferation, growth, and synaptogenesis”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“loss of FMRP resulted in enhanced mTOR signaling and subsequent increased formation of the eukaryotic initiation factor complex 4F (eIF4F) in a mouse model of FXS [290].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [290] Sharma A Hoeffer CA Takayasu Y Dysregulation of mTOR signaling in fragile X syndrome J Neurosci 2010 30 2 694 702 20071534 PMC3665010
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“DISC1 interacts with and suppressed KIAA1212, an Akt signaling enhancer”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [261] Kim JY Duan X Liu CY DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212 Neuron 2009 63 6 761 73 19778506 PMC3075620
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hippocampal TSC1-knockout neurons exhibited mTOR hyperactivity, decreased inhibitory transmission (yet no changes in excitatory transmission), and network hyperexcitability [47] but normal spine density and size [288].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [47] Bateup HS Johnson CA Denefrio CL Saulnier JL Kornacker K Sabatini BL Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis Neuron 2013 78 3 510 22 23664616 PMC3690324
- Not checked yetcites [288] Bateup HS Takasaki KT Saulnier JL Denefrio CL Sabatini BL Loss of Tsc1 in vivo impairs hippocampal mGluR-LTD and increases excitatory synaptic function J Neurosci 2011 31 24 8862 9 21677170 PMC3133739
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Structurally tetrameric, they contain two NR1 obligatory subunits and either two NR2 (A, B, C or D) or two NR3 (A or B) subunits”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“targeted inhibition of p110δ increased Akt Thr308 phosphorylation and reversed PPI deficits in a neurodevelopmental rat model of SCZ [281]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [281] Law AJ Wang Y Sei Y Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110delta inhibition as a potential therapeutic strategy Proceedings of the National Academy of Sciences of the United States of America 2012 109 30 12165 70 22689948 PMC3409795
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“make NMDARs the predominant molecular devices for controlling complex experience-dependent synaptic remodeling and long-lasting synaptic changes, which are crucial for associative learning, working memory, behavioral flexibility or attention [297].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
What the sources say
- Not checked yetcites [297] Lisman J Schulman H Cline H The molecular basis of CaMKII function in synaptic and behavioural memory Nat Rev Neurosci 2002 3 3 175 90 11994750
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“mice with dentate gyrus-specific DISC1 knockdown exhibited schizophrenic-like symptoms including cognitive deficits and anxiety, but rapamycin injection was able to rescue these defects in a time-sensitive manner [278].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [278] Zhou M Li W Huang S mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons Neuron 2013 77 4 647 54 23439118 PMC3586374
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Dysregulation of these processes can impact channel function and expression and alter synaptic transmission [298, 299].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
What the sources say
- Not checked yetcites [298] Lau CG Zukin RS NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders Nat Rev Neurosci 2007 8 6 413 26 17514195
- Not checked yetcites [299] Gladding CM Raymond LA Mechanisms underlying NMDA receptor synaptic/extrasynaptic distribution and function Mol Cell Neurosci 2011 48 4 308 20 21600287
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“NRG-1 induces the phosphorylation of the ErbB4 receptors, which then become docking sites for upstream mTOR molecules such as PI3K [279].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [279] Fuller SJ Sivarajah K Sugden PH ErbB receptors, their ligands, and the consequences of their activation and inhibition in the myocardium J Mol Cell Cardiol 2008 44 5 831 54 18430438
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“removal of TSC1 throughout the cortex, subcortical gray matter, and hippocampal CA3 and hilar neurons produced mice with spontaneous seizures by day 5 and death within 3–5 weeks [287].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [287] Meikle L Talos DM Onda H A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival J Neurosci 2007 27 21 5546 58 17522300 PMC6672762
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Loss of PTEN hyperactivated mTOR, but surprisingly also enhanced both excitatory and inhibitory neurotransmission in the hippocampus [289] and increased spine density [213].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [289] Weston MC Chen H Swann JW Loss of mTOR repressors Tsc1 or Pten has divergent effects on excitatory and inhibitory synaptic transmission in single hippocampal neuron cultures Front Mol Neurosci 2014 7 1 24574959 PMC3922082
- Not checked yetcites [213] Kwon CH Luikart BW Powell CM Pten regulates neuronal arborization and social interaction in mice Neuron 2006 50 3 377 88 16675393 PMC3902853
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“NMDARs exist as multiple subtypes - with each having uniquely physiological and pharmacological properties - and are spatially and developmentally regulated and differentially distributed across neuronal subtypes [296].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
What the sources say
- Not checked yetcites [296] Paoletti P Bellone C Zhou Q NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease Nat Rev Neurosci 2013 14 6 383 400 23686171
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“observations of macrocephaly and epilepsy in 10–30% of the patients with ASD [286].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [286] Bourgeron T A synaptic trek to autism Curr Opin Neurobiol 2009 19 2 231 4 19545994
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“A prominent hypothesis for SCZ pathophysiology posits that NMDARs on PV+ neurons are hypofunctional, thus resulting in lowered GABAergic signaling, overstimulation of excitatory neurons, and a consequent loss of gamma wave oscillations [58].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [58] Gonzalez-Burgos G Lewis DA GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia Schizophr Bull 2008 34 5 944 61 18586694 PMC2518635
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“a MECP2-overexpression mouse also has elevated mTOR signaling [291] while a MECP2-knockout model displays the opposite effects [292].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and ASD
What the sources say
- Not checked yetcites [291] Jiang M Ash RT Baker SA Dendritic arborization and spine dynamics are abnormal in the mouse model of MECP2 duplication syndrome J Neurosci 2013 33 50 19518 33 24336718 PMC3858623
- Not checked yetcites [292] Ricciardi S Boggio EM Grosso S Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model Hum Mol Genet 2011 20 6 1182 96 21212100
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“over-expression of dysbindin-1 in cortical neurons has a neuroprotective effect against apoptosis via PI3K/Akt pathway activation while knockdown has the opposite effect [285].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [285] Numakawa T Yagasaki Y Ishimoto T Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia Hum Mol Genet 2004 13 21 2699 708 15345706
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors essential for mediating ion flux and hence are clearly positioned to control E/I balance at the synaptic level.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“NRG1-ErbB4 and PI3K-Akt are involved in neural circuit development and synaptic plasticity [87, 284]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > mTOR SIGNALING > mTOR and SCZ
What the sources say
- Not checked yetcites [87] Fazzari P Paternain AV Valiente M Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling Nature 2010 464 7293 1376 80 20393464
- Not checked yetcites [284] Cuesto G Enriquez-Barreto L Carames C Phosphoinositide-3-kinase activation controls synaptogenesis and spinogenesis in hippocampal neurons J Neurosci 2011 31 8 2721 33 21414895 PMC6623769
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“chronic MK-801 treatment in rats enhanced ErbB4’s association with PSD-95 and increased ErbB4’s phosphorylation levels [313].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [313] Li JT Feng Y Su YA Wang XD Si TM Enhanced interaction among ErbB4, PSD-95 and NMDAR by chronic MK-801 treatment is associated with behavioral abnormalities Pharmacol Biochem Behav 2013 108 44 53 23603030
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“NL1 may interact with NMDARs through PSD-95 via its C-terminal PDZ domain [331]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [331] Irie M Hata Y Takeuchi M Binding of neuroligins to PSD-95 Science 1997 277 5331 1511 5 9278515
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“suggesting NL1 is required for NMDAR-mediated currents, normal LTP function, and specific behavioral tasks.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [192] Blundell J Blaiss CA Etherton MR Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior J Neurosci 2010 30 6 2115 29 20147539 PMC2824441
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Shank3 - a scaffold protein which acts to traffic NMDAR to synapses”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [327] Duffney LJ Wei J Cheng J Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism J Neurosci 2013 33 40 15767 78 24089484 PMC3787498
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A recent study showed NL1-PSD95 interactions to be neither necessary nor sufficient for NMDARs recruitment to postsynaptic sites”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [330] Budreck EC Kwon OB Jung JH Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling Proceedings of the National Academy of Sciences of the United States of America 2013 110 2 725 30 23269831 PMC3545745
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“both deficits are rescued with NMDAR partial agonist D-cycloserine or through enhancement of NMDAR activity via a positive allosteric modulator of mGluR5 [209].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [209] Won H Lee HR Gee HY Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function Nature 2012 486 7402 261 5 22699620
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This effect was blocked by an actin stabilizer but mimicked with an actin destabilizer and a Rac1 or PAK inhibitor [327]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [327] Duffney LJ Wei J Cheng J Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism J Neurosci 2013 33 40 15767 78 24089484 PMC3787498
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ErbB4 is enriched in the PSD and its association with PSD-95 results in enhancement of NRG1-dependent signaling [83].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [83] Huang YZ Won S Ali DW Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses Neuron 2000 26 2 443 55 10839362
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“which is also consistent with previous postmortem binding studies showing significant alterations in total NMDA receptor complexes only in particular regions of the Rett syndrome brain [336, 337].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [336] Blue ME Naidu S Johnston MV Development of amino acid receptors in frontal cortex from girls with Rett syndrome Ann Neurol 1999 45 4 541 5 10211484
- Not checked yetcites [337] Blue ME Naidu S Johnston MV Altered development of glutamate and GABA receptors in the basal ganglia of girls with Rett syndrome Exp Neurol 1999 156 2 345 52 10328941
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“MECP2-null mice to have decreases in overall NR2A/NR2B ratio and NR1 levels at the synapses compared to wildtype [332]”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [332] Maliszewska-Cyna E Bawa D Eubanks JH Diminished prevalence but preserved synaptic distribution of N-methyl-D-aspartate receptor subunits in the methyl CpG binding protein 2(MeCP2)-null mouse brain Neuroscience 2010 168 3 624 32 20381590
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“SHANK2 mutant mice have autistic-like behaviors and decreased functional NMDARs”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [209] Won H Lee HR Gee HY Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function Nature 2012 486 7402 261 5 22699620
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“which is consistent with attenuated synaptic maturation [333, 334] and fewer overall functional NMDA receptors respectively”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [333] Townsend M Yoshii A Mishina M Constantine-Paton M Developmental loss of miniature N-methyl-D-aspartate receptor currents in NR2A knockout mice Proceedings of the National Academy of Sciences of the United States of America 2003 100 3 1340 5 12552130 PMC298774
- Not checked yetcites [334] Fu Z Logan SM Vicini S Deletion of the NR2A subunit prevents developmental changes of NMDA-mEPSCs in cultured mouse cerebellar granule neurones J Physiol 2005 563 Pt 3 867 81 15649973 PMC1665615
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“NLGN1-knockout mice have deficits in spatial learning and memory as well as repetitive behavior, which corresponded with impaired hippocampal LTP and decreased NMDA/AMPA ratio [192].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [192] Blundell J Blaiss CA Etherton MR Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior J Neurosci 2010 30 6 2115 29 20147539 PMC2824441
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a PV-specific GRIN1-knockout mouse model displaying pyramidal cell hyperexcitability, neural synchrony reductions, and schizophrenic-like behaviors [306].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [306] Belforte JE Zsiros V Sklar ER Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes Nat Neurosci 2010 13 1 76 83 19915563 PMC2797836
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“bath perfusion of mouse prefrontal cortex (PFC) brain slices with NRG1 decreased NMDAR-mediated EPSCs via internalization of the NR1 subunit, with this effect being blocked by ErbB4 inhibitors [312].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [312] Gu Z Jiang Q Fu AK Ip NY Yan Z Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex J Neurosci 2005 25 20 4974 84 15901778 PMC6724849
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This was verified using immunoelectron microscopy images and with a MK-801 wash-out paradigm [330].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [330] Budreck EC Kwon OB Jung JH Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling Proceedings of the National Academy of Sciences of the United States of America 2013 110 2 725 30 23269831 PMC3545745
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“patients had reduced Shank3 expression and major defects in excitatory transmission due partially to decreased NMDA receptors and reduced excitatory synapses”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [328] Shcheglovitov A Shcheglovitova O Yazawa M SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients Nature 2013 503 7475 267 71 24132240 PMC5559273
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“leading to reduced CA1 LTP, and deficits in hippocampus-dependent spatial learning and memory [329].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [329] Kouser M Speed HE Dewey CM Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission J Neurosci 2013 33 47 18448 68 24259569 PMC3834052
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“RNAi knockdown of Shank3 in culture leads to reduction of NMDAR-mediated synaptic current as well as loss of NR1 surface expression.”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [327] Duffney LJ Wei J Cheng J Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism J Neurosci 2013 33 40 15767 78 24089484 PMC3787498
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a recent large study from the Consortium on the Genetics of Schizophrenia verified this connection and also discovered several genes encoding for NR1 interacting proteins associated with the disease [309].”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and SCZ
What the sources say
- Not checked yetcites [309] Greenwood TA Lazzeroni LC Murray SS Analysis of 94 candidate genes and 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia Am J Psychiatry 2011 168 9 930 46 21498463 PMC3751972
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“FMR1-knockout mice had diminished LTP and lowered NMDA/AMPA ratio in the dentate gyrus (DG)”
§ Common Mechanisms of Excitatory and Inhibitory Imbalance in Schizophrenia and Autism Spectrum Disorders > NMDAR SIGNALING > NMDAR Hypofunction and ASD
What the sources say
- Not checked yetcites [340] Eadie BD Cushman J Kannangara TS Fanselow MS Christie BR NMDA receptor hypofunction in the dentate gyrus and impaired context discrimination in adult Fmr1 knockout mice Hippocampus 2012 22 2 241 54 21049485
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Behavioral phenotypes in rodent models described as schizophrenia-like or autism-like correspond to the human disorders.
“mice lacking ErbB4 in the CNS show reduced spine density in both the hippocampus and cortex and exhibit schizophrenia-related behavioral phenotypes [84].”
The paper relies on this without support.
Postmortem brain findings reflect antemortem pathophysiological processes relevant to the disease.
“Postmortem studies have examined brain regions showing the highest indices of gray matter loss and have consistently found reductions in spine density in these parts.”
The paper relies on this without support.
Spine density changes observed in animal models are relevant to human SCZ and ASD pathophysiology.
“Primary hippocampal neurons from mice engineered to carry hemizygous deletion of the 1.3-Mb orthologous chromosomal region (Df(16)A+/−) showed reduced spine density and sizes [107].”
The paper relies on this without support.
A significant symptom overlap exists between ASD and SCZ.
“a significant overlap in symptoms exists”
The paper relies on this without support.
FXS, like many developmental disorders, involves synaptic plasticity changes that may impair learning and memory.
“Like many developmental disorders, FXS is associated with alterations in synaptic plasticity that may impair learning and memory processes in the brain.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Dysfunction and/or deficient inhibitory output from PV interneurons may be a common mechanism of multiple psychiatric disorders, such as schizophrenia (SCZ) (Lewis et al. 2005), autism spectrum disorders (ASD) (Gao and Penzes 2015) and bipolar disorder (BD) (Ruden et al. 2021).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Gao and Penzes 2015
Citations
Cites
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181 · cited 1×
“For a more comprehensive picture of mTOR’s function and other pertinent molecular players and pathways, we direct the reader to a more comprehensive review [269].”
BackgroundInterneurons of the neocortical inhibitory system
Markram, H., Toledo-Rodriguez, M., Wang, Y., Gupta, A., Silberberg, G., & Wu, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1519 · Cited by 2,954 · cited 12×
“Evidence for alterations in GABAergic circuits in ASD also come from postmortem studies showing significantly reduced GAD65/GAD67 levels in the parietal cortex and cerebellum [145, 146] and alterations in GABAA and GABAB receptors in postmortem brains of autistic subjects [147–149].”
BackgroundInfluentialDefining the role of mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833 · cited 1×
“The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that responds to environmental signals by controlling cell growth and proliferation [263, 264], synaptogenesis [213], and dendrite [265, 266] and axon growth [213, 267] in neurons via regulation of protein translation and hence plays an important ro…”
BackgroundModel of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768 · cited 1×
“Early brain overgrowth and neuronal hyperexcitability are two well-established phenotypes in ASD [135, 136].”
BackgroundNMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
Paoletti, P., Bellone, C., & Zhou, Q. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3504 · Cited by 2,523 · cited 1×
“As a result, NMDARs exist as multiple subtypes - with each having uniquely physiological and pharmacological properties and are spatially and developmentally regulated and differentially distributed across neuronal subtypes [296].”
BackgroundNeocortical excitation/inhibition balance in information processing and social dysfunction
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., et al. (2011) · Nature · doi:10.1038/nature10360 · Cited by 2,454 · cited 1×
“Moreover, optogenetic manipulation of specific excitatory and inhibitory circuits directly caused changes in social and cognitive behavior in mice [48].”
BackgroundCortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297 · cited 1×
“found the absolute number of PV+ cells unchanged, suggesting a functional rather than a numerical deficit [64, 65].”
BackgroundActivity-dependent scaling of quantal amplitude in neocortical neurons
Turrigiano, G. G., Leslie, K. R., Desai, N. S., Rutherford, L. C., & Nelson, S. B. (1998) · Nature · doi:10.1038/36103 · Cited by 2,226 · cited 1×
“[39] discovered chronic activity blockade with tetrodotoxin (TTX) and bicuculline increased and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSC) respectively in cultured neurons, while drug washout restored firing rates to control levels.”
BackgroundAbnormal neural oscillations and synchrony in schizophrenia
Uhlhaas, P. J., & Singer, W. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2774 · Cited by 2,120 · cited 1×
“Fittingly, gamma-frequency oscillations are abnormal in the prefrontal cortex of patients with SCZ who are performing working-memory tasks [45, 62, 63].”
BackgroundSynaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks
Bartos, M., Vida, I., & Jonas, P. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2044 · Cited by 2,070 · cited 1×
“amplitude) is modulated by the E/I balance at distinct synaptic sites in the circuit and the intrinsic excitable properties of the neurons [46].”
Background
Cited by
Sorted by citations
Maternal immune activation: Implications for neuropsychiatric disorders
Estes, M. L., & McAllister, A. K. (2016) · Science · doi:10.1126/science.aag3194 · Cited by 1,206
Ferguson, B. R., & Gao, W.-J. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00037 · Cited by 594
“Intriguingly, this pattern repeats among multiple psychiatric disorders including ASD, depression, and intellectual disability (Gao and Penzes, 2015; Luscher and Fuchs, 2015).”
BackgroundHoward, D. M., Adams, M. J., Shirali, M., Clarke, T.-K., Marioni, R. E., Davies, G., Coleman, J. R. I., Alloza, C., Shen, X., Barbu, M. C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03819-3 · Cited by 612
Dendritic structural plasticity and neuropsychiatric disease
Forrest, M. P., Parnell, E., & Penzes, P. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.16 · Cited by 464
Self-citationAstrocytic neuroligins control astrocyte morphogenesis and synaptogenesis
Stogsdill, J. A., Ramirez, J., Liu, D., Kim, Y. H., Baldwin, K. T., Enustun, E., Ejikeme, T., Ji, R.-R., & Eroglu, C. (2017) · Nature · doi:10.1038/nature24638 · Cited by 506
“NL dysfunction in disease is postulated to alter the fine balance between inhibition and excitation in the brain 38 .”
Background
Metadata
- Authors
- Gao, R., & Penzes, P.
- Affiliations
- Northwestern University (US)
- ORCID
- Penzes, P.
- Venue
- Current Molecular Medicine
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-03-18
- Volume
- 15
- Issue
- 2
- Pages
- 146-167
- ISSN
- 1566-5240 (ISSN-L)
- PMC
- PMC4721588
- OpenAlex
- W2334244908
- Semantic Scholar
- b6b53ecd1928312e333aef0b5f5b4a187daf721f
- Cited by
- 516
- References
- 339
- Citations by year
- 2026: 27 · 2025: 53 · 2024: 51 · 2023: 57 · 2022: 59 · 2021: 75 · 2020: 66 · 2019: 39 · 2018: 42 · 2017: 32 · 2016: 11 · 2015: 4
- FWCI
- 13.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (F30MH096457, R01MH071316)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- excitatory-inhibitory imbalance, schizophrenia, autism spectrum disorder, shared pathophysiology, glutamatergic circuits, inhibitory interneurons, genetic architecture, neuropathology, therapeutic target
- MeSH terms
- Autism Spectrum Disorder, Gene Expression Regulation, Humans, Interneurons, Nerve Tissue Proteins, Synaptic Transmission, Schizophrenia, Synapses, Receptors, N-Methyl-D-Aspartate, Pyramidal Cells, Genetic Predisposition to Disease, Dendritic Spines, TOR Serine-Threonine Kinases, GABAergic Neurons
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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