The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
Cognitive Dysfunction in Schizophrenia: Convergence of γ-Aminobutyric Acid and Glutamate Alterations
Abstract
Impairments in certain cognitive functions mediated by the dorsolateral prefrontal cortex, such as working memory, are core features of schizophrenia. Convergent findings suggest that these disturbances are associated with alterations in markers of inhibitory gamma-aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced gamma-aminobutyric acid synthesis is present in the subpopulation of gamma-aminobutyric acid neurons that express the calcium-binding protein parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the resulting impaired inhibitory regulation of pyramidal neurons contributes to a reduction in the synchronized neuronal activity that is required for working memory function. Several lines of evidence suggest that these changes may be either secondary to or exacerbated by impaired signaling via the N-methyl-d-aspartate class of glutamate receptors. These findings suggest specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Diminished activation of NMDA-receptors results in insufficient excitatory activity, disrupting the monitoring function of GABAergic inhibitory neurons.”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [80]
In the citing paper
“In response, these inhibitory neurons may downregulate their own activity.79,80”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [80]
In the citing paper
“The prefrontal cortex (PFC) and hippocampus stand out as major regions affected in schizophrenia”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [2]
Citations
Cites
Krystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297
Self-citationSchizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020
Schizophrenia as a Disorder of Neurodevelopment
Lewis, D. A., & Levitt, P. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142754 · Cited by 1,163
Self-citationAkbarian, S. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950160008002 · Cited by 1,002
Hashimoto, T., Volk, D. W., Eggan, S. M., Mirnics, K., Pierri, J. N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06315.2003 · Cited by 938
Self-citationCognitive Impairment in Schizophrenia Is the Core of the Disorder
Elvevag, B., & Goldberg, T. E. (2000) · Critical Reviews™ in Neurobiology · doi:10.1615/critrevneurobiol.v14.i1.10 · Cited by 835 · cited 1×
“Although psychosis is usually the most striking clinical aspect of schizophrenia, disturbances in certain cognitive processes, such as attention, certain types of memory, and executive functions, are considered to be the core features of the illness.(4) Such cognitive disturbances (1) can be present for years before t…”
BackgroundLewis, D. A., & Lieberman, J. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)00111-2 · Cited by 833
Self-citationGamma Oscillations Correlate with Working Memory Load in Humans
Howard, M. W. (2003) · Cerebral Cortex · doi:10.1093/cercor/bhg084 · Cited by 766
Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.3.237 · Cited by 697
Self-citationKeefe, R. S. E., Silva, S. G., Perkins, D. O., & Lieberman, J. A. (1999) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a033374 · Cited by 695
Complexity of Prefrontal Cortical Dysfunction in Schizophrenia: More Than Up or Down
Callicott, J. H., Mattay, V. S., Verchinski, B. A., Marenco, S., Egan, M. F., & Weinberger, D. R. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.12.2209 · Cited by 673
Relation of Prefrontal Cortex Dysfunction to Working Memory and Symptoms in Schizophrenia
Perlstein, W. M., Carter, C. S., Noll, D. C., & Cohen, J. D. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.7.1105 · Cited by 652
Interneuron Diversity series: Inhibitory interneurons and network oscillations in vitro
Whittington, M. A., & Traub, R. D. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.09.016 · Cited by 506
Gulyás, A. I., Megı́as, M., Emri, Z., & Freund, T. F. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-22-10082.1999 · Cited by 476
Verma, A., & Moghaddam, B. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-01-00373.1996 · Cited by 451
Self-citationA subclass of prefrontal γ-aminobutyric acid axon terminals are selectively altered in schizophrenia
Woo, T.-U. W., Whitehead, R. E., Melchitzky, D. S., & Lewis, D. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5341 · Cited by 410
Self-citationWorking Memory Deficit as a Core Neuropsychological Dysfunction in Schizophrenia
Silver, H., Feldman, P., Bilker, W. B., & Gur, R. C. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.10.1809 · Cited by 410
Rao, S. G., Williams, G. V., & Goldman-Rakic, P. S. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00485.2000 · Cited by 407
Bringing Order to the Glutamate Chaos in Schizophrenia
Moghaddam, B. (2003) · Neuron · doi:10.1016/s0896-6273(03)00757-8 · Cited by 403
Self-citationCognitive deficits as treatment targets in schizophrenia
Gold, J. M. (2004) · Schizophrenia Research · doi:10.1016/j.schres.2004.09.008 · Cited by 350
Adler, C. M., Malhotra, A. K., Elman, I., Goldberg, T. E., Egan, M. F., Pickar, D., & Breier, A. F. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.10.1646 · Cited by 337
Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment
Konradi, C., & Heckers, S. (2003) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00328-5 · Cited by 336
The molecular genetics of schizophrenia: new findings promise new insights
Owen, M. J., Williams, N. M., & O’Donovan, M. C. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001444 · Cited by 328
MacDonald, A. W., Carter, C. S., Kerns, J. G., Ursu, S., Barch, D. M., Holmes, A. J., Stenger, V. A., & Cohen, J. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.3.475 · Cited by 324
Volk, D. W. (2002) · Cerebral Cortex · doi:10.1093/cercor/12.10.1063 · Cited by 264
Homayoun, H., Stefani, M. R., Adams, B. W., Tamagan, G. D., & Moghaddam, B. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300417 · Cited by 255
Self-citationCochran, S. M., Kennedy, M., McKerchar, C. E., Steward, L. J., Pratt, J. A., & MORRIS, B. J. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300031 · Cited by 236
Coyle, J. T., & Tsai, G. E. (2003) · Psychopharmacology · doi:10.1007/s00213-003-1709-2 · Cited by 230
Volk, D. W., Austin, M. C., Pierri, J. N., Sampson, A. R., & Lewis, D. A. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.2.256 · Cited by 221
Self-citationA Placebo-Controlled Pilot Study of the Ampakine CX516 Added to Clozapine in Schizophrenia
GOFF, D. C., Leahy, L., Berman, I., Posever, T. A., Herz, L. R., Leon, A. C., Johnson, S. A., & LYNCH, G. S. (2001) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200110000-00005 · Cited by 209
The GABA-glutamate connection in schizophrenia: which is the proximate cause?
Coyle, J. T. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.07.034 · Cited by 194
Targeting metabotropic glutamate receptors for treatment of the cognitive symptoms of schizophrenia
Moghaddam, B. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1792-z · Cited by 189
Self-citationLipska, B. K., Lerman, D. N., Khaing, Z. Z., Weickert, C. S., & Weinberger, D. R. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02738.x · Cited by 104
Homayoun, H., & Moghaddam, B. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhi087 · Cited by 84
Self-citationMelchitzky, D. S. (2003) · Cerebral Cortex · doi:10.1093/cercor/13.5.452 · Cited by 84
Gonzalez-Albo, M. C. (2001) · Cerebral Cortex · doi:10.1093/cercor/11.12.1170 · Cited by 77
Marenco, S., Egan, M. F., Goldberg, T. E., Knable, M. B., McClure, R. K., Winterer, G., & Weinberger, D. R. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00311-5 · Cited by 69
Huntley, G. W., Vickers, J. C., & Morrison, J. H. (1997) · Brain Research · doi:10.1016/s0006-8993(96)00847-5 · Cited by 47
Impact of neuroleptic medications on continuous performance test measures in schizophrenia
Epstein, J. I., Keefe, R. S. E., Roitman, S. L., Harvey, P. D., & Mohs, R. C. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00588-9 · Cited by 32
Cited by
Sorted by citations
Animal models of neuropsychiatric disorders
Nestler, E. J., & Hyman, S. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2647 · Cited by 2,023
Neuregulin 1 in neural development, synaptic plasticity and schizophrenia
Mei, L., & Xiong, W.-C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2392 · Cited by 1,030
Lisman, J. E., Coyle, J. T., Green, R. W., Javitt, D. C., Benes, F. M., Heckers, S., & Grace, A. A. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.005 · Cited by 1,010
Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases
Mei, L., & Nave, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.06.007 · Cited by 616
The GABA system in anxiety and depression and its therapeutic potential
Möhler, H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.040 · Cited by 627
Metadata
- Authors
- Lewis, D. A., & Moghaddam, B.
- Affiliations
- University of Pittsburgh (US)
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2006-10-01
- Volume
- 63
- Issue
- 10
- Pages
- 1372
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2037549116
- Cited by
- 404
- References
- 41
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 11 · 2019: 12 · 2018: 16 · 2017: 13 · 2016: 17 · 2015: 22 · 2014: 28 · 2013: 25 · 2012: 39
- FWCI
- 20.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (5r01mh048404-30, MH043784, MH045156)
- National Institute of Mental Health (MH-045156, R01-MH048404, MH051234, R37MH048404, R01MH051234, P50MH045156, MH065026, R21MH065026, MH043784, MH048404)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, cognitive impairment, working memory, dorsolateral prefrontal cortex, GABAergic inhibition, glutamatergic excitation, parvalbumin, NMDA receptor, neuronal synchronization, therapeutic target
- MeSH terms
- Animals, Cognition Disorders, gamma-Aminobutyric Acid, Humans, Neural Inhibition, Synaptic Transmission, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, Pyramidal Cells, Glutamic Acid
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
