GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon

Guidotti, Alessandro; Auta, James; Davis, John M.; Dong, Erbo; Grayson, Dennis R.; Veldic, Marin; Zhang, Xianquan; Costa, Erminio

doi:10.1007/s00213-005-2212-8

Cited by 264Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon

Guidotti, Alessandro, Auta, James, Davis, John M., Dong, Erbo, Grayson, Dennis R., Veldic, Marin, Zhang, Xianquan, Costa, Erminio·2005·Psychopharmacology

DOI 10.1007/s00213-005-2212-8

Open this paper in CoChat — free account

Abstract

Rationale Cortical gamma-aminobutyric acid (GABA)ergic neurons contribute to the orchestration of pyramidal neuron population firing as follows: (1) by releasing GABA on GABA(A) and GABA(B) receptors, (2) by releasing reelin in the proximity of integrin receptors located on cortical pyramidal neuron dendritic spines, and (3) through reelin contributing to the regulation of dendritic spine plasticity by modulating dendritic resident mRNA translation. In schizophrenia (SZ) and bipolar (BP) postmortem brains, the downregulation of mRNAs encoding glutamic acid decarboxylase 67 (GAD(67)) and reelin decreases the cognate proteins coexpressed in prefrontal cortex (PFC) GABAergic neurons. This finding has been replicated in several laboratories. Such downregulation suggests that the neuropil hypoplasticity found in the PFC of SZ and BP disorder patients may depend on a downregulation of GABAergic function, which is associated with a decrease in reelin secretion from GABAergic neuron axon terminals on dendrites, somata, or axon initial segments of pyramidal neurons. Indirectly, this GABAergic neuron downregulation may play a key role in the expression of positive and negative symptoms of SZ and BP disorders.Objectives The above described GABAergic dysfunction may be addressed by pharmacological interventions to treat SZ and BP disorders using specific benzodiazepines (BZs), which are devoid of intrinsic activity at GABA(A) receptors including alpha(1) subunits but that act as full positive allosteric modulators of GABA action at GABA(A) receptors containing alpha(2), alpha(3), or alpha(5) subunits. These drugs are expected to enhance GABAergic signal transduction without eliciting sedation, amnesia, and tolerance or dependence liabilities.Results and conclusions BZs, such as diazepam, although they are efficient in equilibrating GABA(A) receptor signal transduction in a manner beneficial in the treatment of positive and negative symptoms of SZ, may not be ideal drugs, because by mediating a full positive allosteric modulation of GABA(A) receptors containing the alpha(1) subunit, they contribute to sedation and to the development of tolerance after even a brief period of treatment. In contrast, other BZ-binding site ligands, such as 6-(2bromophenyl)-8-fluoro-4H-imidazo [1,5-a][1,4] benzodiazepine-3-carboxamide (imidazenil), which fail to allosterically and positively modulate the action of GABA at GABA(A) receptors with alpha(1) subunits but that selectively allosterically modulate cortical GABA(A) receptors containing alpha(5) subunits, contribute to the anxiolytic, antipanic, and anticonvulsant actions of these ligands without producing sedation, amnesia, or tolerance. Strong support for the use of imidazenil in psychosis emerges from experiments with reeler mice or with methionine-treated mice, which express a pronounced reelin and GAD(67) downregulation that is also operative in SZ and BP disorders. In mice that model SZ symptoms, imidazenil increases signal transduction at GABA(A) receptors containing alpha(5) subunits and contributes to the reduction of behavioral deficits without producing sedation or tolerance liability. Hence, we suggest that imidazenil may be considered a prototype for a new generation of positive allosteric modulators of GABA(A) receptors, which, either alone or in combination with neuroleptics, should be evaluated in GABAergic dysfunction operative in the treatment of SZ and BP disorders with psychosis.

Integrity signals

Registry

Crossref · 10.1007/s00213-005-2212-8

Cites

104 of 104 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Benzodiazepines are heavily used as adjuvant treatment in schizophrenia.
“Remarkably, benzodiazepines are heavily used as adjuvant treatment in schizophrenia, 80”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [80]

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
A framework for consciousness
Crick, F., & Koch, C. (2003) · Nature Neuroscience · doi:10.1038/nn0203-119 · Cited by 1,492 · see citing works
Structure and pharmacology of gamma-aminobutyric acidA receptor subtypes.
Sieghart, W. (1995) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06840-1 · Cited by 1,301 · see citing works
GABA A ‐receptor heterogeneity in the adult rat brain: Differential regional and cellular distribution of seven major subunits
Fritschy, J., & Mohler, H. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903590111 · Cited by 1,244 · see citing works
Decrease in Reelin and Glutamic Acid Decarboxylase67 (GAD67) Expression in Schizophrenia and Bipolar Disorder
Guidotti, A., Auta, J., Davis, J. M., Gerevini, V. D. G., Dwivedi, Y., Grayson, D. R., Impagnatiello, F., Pandey, G. N., Pesold, C., Sharma, R. P., et al. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.11.1061 · Cited by 1,203 · see citing works
Self-citation
GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder
Benes, F. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00225-1 · Cited by 1,082 · see citing works
Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics.
Akbarian, S. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950160008002 · Cited by 1,002 · see citing works
The pyramidal neuron of the cerebral cortex: Morphological and chemical characteristics of the synaptic inputs
DeFelipe, J., & Fariñas, I. (1992) · Progress in Neurobiology · doi:10.1016/0301-0082(92)90015-7 · Cited by 975 · see citing works
Differences between somatic and dendritic inhibition in the hippocampus
Miles, R., Tóth, K., Gulyás, A. I., Hájos, N., & Freund, T. F. (1996) · Neuron · doi:10.1016/s0896-6273(00)80101-4 · Cited by 942 · see citing works
The reduced neuropil hypothesis: a circuit based model of schizophrenia
Selemon, L. D., & Goldman-Rakic, P. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00281-9 · Cited by 909 · see citing works
Handbook of Experimental Pharmacology, vol 14.
Freedman, A. D. (1972) · Archives of Internal Medicine · doi:10.1001/archinte.1972.03650020118031 · Cited by 777 · see citing works
A decrease of reelin expression as a putative vulnerability factor in schizophrenia
Impagnatiello, F., Guidotti, A. R., Pesold, C., Dwivedi, Y., Caruncho, H. J., Pisu, M. G., Uzunov, D. P., Smalheiser, N. R., Davis, J. M., Pandey, G. N., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15718 · Cited by 753 · see citing works
Self-citation
Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence.
Carlsson, A., Waters, N., Holm-Waters, S., Tedroff, J., Nilsson, M., & Carlsson, M. (2001) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.237 · Cited by 742 · see citing works
Decreased Glutamic Acid Decarboxylase67 Messenger RNA Expression in a Subset of Prefrontal Cortical γ-Aminobutyric Acid Neurons in Subjects With Schizophrenia
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 · see citing works
Role of the Reelin Signaling Pathway in Central Nervous System Development
Rice, D. S., & Curran, T. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1005 · Cited by 667 · see citing works
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 647 · see citing works
Two isoforms of glutamate decarboxylase: why?
Soghomonian, J., & Martin, D. L. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(98)01270-x · Cited by 643 · see citing works
The Contribution of the Anterior Cingulate Cortex to Executive Processes in Cognition
Carter, C. S., Botvinick, M., & Cohen, J. D. (1999) · Reviews in the Neurosciences · doi:10.1515/revneuro.1999.10.1.49 · Cited by 624 · see citing works
Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning
Weeber, E. J., Beffert, U., Jones, C., Christian, J. M., Förster, E., Sweatt, J. D., & Herz, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205147200 · Cited by 623 · see citing works
Neural synchrony indexes disordered perception and cognition in schizophrenia
Spencer, K., Nestor, P. G., Perlmutter, R., Niznikiewicz, M. A., Klump, M. C., Frumin, M., Shenton, M. E., & McCarley, R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406074101 · Cited by 591 · see citing works
Structural and functional basis for GABAA receptor heterogeneity
Levitan, E. S., Schofield, P. R., Burt, D. R., Rhee, L. M., Wisden, W., Köhler, M. G., Fujita, N., Rodriguez, H., Stephenson, A., Darlison, M. G., et al. (1988) · Nature · doi:10.1038/335076a0 · Cited by 589 · see citing works
Interneurons unbound
McBain, C. J., & Fisahn, A. (2001) · Nature Reviews Neuroscience · doi:10.1038/35049047 · Cited by 581 · see citing works
Emerging principles of altered neural circuitry in schizophrenia
Benes, F. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00041-7 · Cited by 513 · see citing works
GABAergic Neurons and Their Role in Cortical Plasticity in Primates
Jones, E. G. (1993) · Cerebral Cortex · doi:10.1093/cercor/3.5.361-a · Cited by 489 · see citing works
Neurosteroid modulation of GABAA receptors
Lambert, J. J., Belelli, D., Peden, D. R., Vardy, A., & Peters, J. A. (2003) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2003.09.001 · Cited by 489 · see citing works
Perceptual Neuroscience: The Cerebral Cortex
Mountcastle, V. B. (1998) · Cited by 481 · see citing works
Specific GABA A Circuits for Visual Cortical Plasticity
Fagiolini, M., Fritschy, J.-M., Löw, K., Möhler, H., Rudolph, U., & Hensch, T. K. (2004) · Science · doi:10.1126/science.1091032 · Cited by 471 · see citing works
Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression
Fatemi, S. H., Earle, J. A., & McMenomy, T. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000783 · Cited by 447 · see citing works
Density of Glutamic Acid Decarboxylase 67 Messenger RNA–ContainingNeurons That Express the N-Methyl-D-AspartateReceptor Subunit NR2A in the Anterior Cingulate Cortex in Schizophreniaand Bipolar Disorder
Woo, T.-U. W., Walsh, J. P., & Benes, F. M. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.7.649 · Cited by 411 · see citing works
A 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 · see citing works
Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium
Knable, M. B., Barci, B. M., Webster, M. J., Meador‐Woodruff, J. H., & Torrey, Ε. F. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001471 · Cited by 407 · see citing works
Destruction and Creation of Spatial Tuning by Disinhibition: GABAABlockade of Prefrontal Cortical Neurons Engaged by Working Memory
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 · see citing works
Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report
Abdolmaleky, H. M., Cheng, K., Russo, A. L., Smith, C. L., Faraone, S. V., Wilcox, M., Shafa, R., Glatt, S. J., Nguyen, G. H., Ponte, J. F., et al. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30140 · Cited by 390 · see citing works
Differential synaptic localization of two major gamma-aminobutyric acid type A receptor alpha subunits on hippocampal pyramidal cells.
Nusser, Z., Sieghart, W., Benke, D., Fritschy, J., & Somogyi, P. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11939 · Cited by 386 · see citing works
An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability
Tremolizzo, L., Carboni, G., Ruzicka, W. B., Mitchell, C. P., Sugaya, I., Tueting, P. A., Sharma, R. P., Grayson, D. R., Costa, E., & Guidotti, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.262658999 · Cited by 381 · see citing works
Self-citation
Compartmentalized Synthesis and Degradation of Proteins in Neurons
Steward, O., & Schuman, E. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00635-4 · Cited by 377 · see citing works
Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway
Niu, S., Renfro, A., Quattrocchi, C. C., Sheldon, M., & D'Arcangelo, G. (2004) · Neuron · doi:10.1016/s0896-6273(03)00819-5 · Cited by 375 · see citing works
Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics
Benes, F., Vincent, S. L., Alsterberg, G., Bird, E. D., & SanGiovanni, J. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-03-00924.1992 · Cited by 367 · see citing works
Isodirectional Tuning of Adjacent Interneurons and Pyramidal Cells During Working Memory: Evidence for Microcolumnar Organization in PFC
Rao, S. G., Williams, G. V., & Goldman, P. S. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.4.1903 · Cited by 335 · see citing works
Differential Hippocampal Expression of Glutamic Acid Decarboxylase 65 and 67 Messenger RNA in Bipolar Disorder and Schizophrenia
Heckers, S., Stone, D., Walsh, J., Shick, J., Koul, P., & Benes, F. M. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.6.521 · Cited by 322 · see citing works
Synapse-specific localization of NMDA and GABAA receptor subunits revealed by antigen-retrieval immunohistochemistry
Fritschy, J., Weinmann, O., Wenzel, A., & Benke, D. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980112)390:2 · Cited by 321 · see citing works
The Physiological Role of 5-HT2AReceptors in Working Memory
Williams, G. V., Rao, S. G., & Goldman-Rakic, P. S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-07-02843.2002 · Cited by 311 · see citing works
DNA-methyltransferase 1 mRNA is selectively overexpressed in telencephalic GABAergic interneurons of schizophrenia brains
Veldić, M., Caruncho, H. J., Liu, W. S., Davis, J. M., Satta, R., Grayson, D. R., Guidotti, A., & Costa, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2637013100 · Cited by 303 · see citing works
Self-citation
Up-regulation of GABAA receptor binding on neurons of the prefrontal cortex in schizophrenic subjects
Benes, F. M., Vincent, S. L., Marie, A. S., & Khan, Y. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00328-4 · Cited by 274 · see citing works
In psychosis, cortical interneurons overexpress DNA-methyltransferase 1
Veldić, M., Guidotti, A., Maloku, E., Davis, J. M., & Costa, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409665102 · Cited by 269 · see citing works
Self-citation
Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice
Tremolizzo, L., Doueiri, M.-S., Dong, E., Grayson, D. R., Davis, J. M., Pinna, G., Tueting, P. A., Rodriguez‐Menendez, V., Costa, E., & Guidotti, A. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.046 · Cited by 257 · see citing works
Self-citation
Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction
Lewis, D., Volk, D., & Hashimoto, T. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1673-x · Cited by 253 · see citing works
Pathology of Layer V Pyramidal Neurons in the Prefrontal Cortex of Patients With Schizophrenia
Black, J. E., Kodish, I. M., Grossman, A. W., Klintsova, A. Y., Orlovskaya, D., Vostrikov, V., Uranova, N., & Greenough, W. T. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.4.742 · Cited by 250 · see citing works
GABA and Schizophrenia: A Review of Basic Science and Clinical Studies
Wassef, A. A., Baker, J. D., & Kochan, L. D. (2003) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000095349.32154.a5 · Cited by 243 · see citing works
Molecular Targets for the Myorelaxant Action of Diazepam
Crestani, F., Löw, K., Keist, R., Mandelli, M.-J., Möhler, H., & Rudolph, U. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.3.442 · Cited by 239 · see citing works
Microcolumns in the cerebral cortex
Jones, E. G. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5019 · Cited by 233 · see citing works
Benzodiazepines in the treatment of schizophrenia: a review and reappraisal
Wolkowitz, O. M., & Pickar, D. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.6.714 · Cited by 221 · see citing works
GABA Transporter-1 mRNA in the Prefrontal Cortex in Schizophrenia: Decreased Expression in a Subset of Neurons
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 · see citing works
Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis
Eastwood, S. L., & Harrison, P. J. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001399 · Cited by 208 · see citing works
Dendritic Spine Hypoplasticity and Downregulation of Reelin and GABAergic Tone in Schizophrenia Vulnerability
Costa, E., Davis, J. M., Grayson, D. R., Guidotti, A., Pappas, G. D., & Pesold, C. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0436 · Cited by 197 · see citing works
Self-citation
Input‐dependent synaptic targeting of α2‐subunit‐containing GABAA receptors in synapses of hippocampal pyramidal cells of the rat
Nyíri, G., Freund, T. F., & Somogyi, P. (2001) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2001.01407.x · Cited by 196 · see citing works
Columnar Architecture Sculpted by GABA Circuits in Developing Cat Visual Cortex
Hensch, T. K., & Stryker, M. P. (2004) · Science · doi:10.1126/science.1091031 · Cited by 189 · see citing works
GABAA Receptor Subunit Gene Expression in Human Prefrontal Cortex: Comparison of Schizophrenics and Controls
Akbarian, S., Huntsman, M. M., Kim, J. J., Tafazzoli, A., Potkin, S. G., Bunney, W. E., & Jones, E. G. (1995) · Cerebral Cortex · doi:10.1093/cercor/5.6.550 · Cited by 181 · see citing works
Segregation of serotonin 5-HT2A and 5-HT3 receptors in inhibitory circuits of the primate cerebral cortex
Jakab, R. L., & Goldman, P. S. (2000) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(20000214)417:3 · Cited by 180 · see citing works
Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis
Eastwood, S. L., & Harrison, P. J. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001371 · Cited by 158 · see citing works
THREADWORMS AND ROUNDWORMS
MUSACCHIO, I. T., PALERMO, N., & RODRIGUEZ, R. R. (1964) · The Lancet · doi:10.1016/s0140-6736(64)92242-1 · Cited by 155 · see citing works
Changes in Serotonin2A and GABAA Receptors in Schizophrenia
Dean, B., Hussain, T., Hayes, W., Scarr, E., Kitsoulis, S., Hill, C., Opeskin, K., & Copolov, D. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721593.x · Cited by 148 · see citing works
Benzodiazepines on trial: a research strategy for their rehabilitation
Costa, E., & Guidetti, A. (1996) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(96)10015-8 · Cited by 143 · see citing works
Self-citation
[3H]Muscimol binding sites increased in autopsied brains of chronic schizophrenics
Hanada, S., Mita, T., Nishino, N., & Tanaka, C. (1987) · Life Sciences · doi:10.1016/0024-3205(87)90341-9 · Cited by 140 · see citing works
Physiological properties of anatomically identified basket and bistratified cells in the CA1 area of the rat hippocampus in vitro
Buhl, E. H., Szil�gyi, T., Halasy, K., & Somogyi, P. (1996) · Hippocampus · doi:10.1002/(sici)1098-1063(1996)6:3 · Cited by 138 · see citing works
Modifications of gamma-aminobutyric acidA receptor subunit expression in rat neocortex during tolerance to diazepam.
Impagnatiello, F., Pesold, C., Longone, P., Caruncho, H. J., Fritschy, J., Costa, E., & Guidotti, A. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09071-6 · Cited by 124 · see citing works
Self-citation
Postnatal development of pre- and postsynaptic GABA markers at chandelier cell connections with pyramidal neurons in monkey prefrontal cortex
Cruz, D. A., Eggan, S. M., & Lewis, D. A. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10833 · Cited by 118 · see citing works
Diazepam Treatment of Early Signs of Exacerbation in Schizophrenia
Carpenter, W. T., Buchanan, R. W., Kirkpatrick, B. W., & Breier, A. F. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.2.299 · Cited by 117 · see citing works
GABAA-receptor subtypes: a new pharmacology
Möhler, H. (2001) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(01)00008-x · Cited by 115 · see citing works
Neurosciences in the Third Millennium: A Tribute to Mimo Costa
Murray, T. F. (2004) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v16.i12.10 · Cited by 111 · see citing works
Delayed response deficits produced by local injection of bicuculline into the dorsolateral prefrontal cortex in Japanese macaque monkeys
Sawaguchi, T., Matsumura, M., & Kubota, K. (1989) · Experimental Brain Research · doi:10.1007/bf00249897 · Cited by 109 · see citing works
Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal Cells*
Chalovich, E. M., Zhu, J.-H., Caltagarone, J., Bowser, R., & Chu, C. T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602632200 · Cited by 108 · see citing works
A reelin–integrin receptor interaction regulates Arc mRNA translation in synaptoneurosomes
Dong, E., Caruncho, H. J., Liu, W., Smalheiser, N. R., Grayson, D. R., Costa, E., & Guidotti, A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031602100 · Cited by 105 · see citing works
Self-citation
Biochemical evidence for two classes of GABA receptors in rat brain
Guidotti, A., Gale, K., Suria, A., & Toffano, G. (1979) · Brain Research · doi:10.1016/0006-8993(79)90590-0 · Cited by 103 · see citing works
Self-citation
Prefrontal Cortical Representation of Visuospatial Working Memory in Monkeys Examined by Local Inactivation With Muscimol
Sawaguchi, T., & Iba, M. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.4.2041 · Cited by 101 · see citing works
The heterozygote reeler mouse as a model for the development of a new generation of antipsychotics
Costa, E. (2002) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(01)00121-7 · Cited by 100 · see citing works
Self-citation
Glutamic acid decarboxylase and glutamate receptor changes during tolerance and dependence to benzodiazepines
Izzo, E., Auta, J., Impagnatiello, F., Pesold, C., Guidotti, A., & Costa, E. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051628698 · Cited by 90 · see citing works
Self-citation
Imidazenil: a new partial positive allosteric modulator of gamma-aminobutyric acid (GABA) action at GABAA receptors.
Giusti, P., Ducic, I., Puia, G., Arban, R., Walser, A., Guidotti, A., & Costa, E. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38411-9 · Cited by 89 · see citing works
Self-citation
GABAA receptor subunit mRNA levels are differentially influenced by chronic FG 7142 and diazepam exposure
Primus, R. J., & Gallager, D. W. (1992) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(92)90078-a · Cited by 88 · see citing works
Part I. Biochemical Studies
Wyatt, R. J., Termini, B. A., & Davis, J. (1971) · Schizophrenia Bulletin · doi:10.1093/schbul/1.4.10 · Cited by 75 · see citing works
Self-citation
Dendritic Spine Density in Schizophrenia and Depression
Glantz, L. A., & Lewis, D. A. (2001) · Archives of General Psychiatry · doi:10.1001/archpsyc.58.2.203 · Cited by 73 · see citing works
Catching up on schizophrenia: natural history and neurobiology.
Lewis, D. A., & Lieberman, J. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)00111-2 · Cited by 71 · see citing works
GABAA receptors and benzodiazepines: a role for dendritic resident subunit mRNAs11This paper is part of a previously published Special Issue (Volume 43/4) that accompanies the 12th Neuropharmacology Conference 2002 entitled ‘GABAA receptors in cellular and network excitability’.
Costa, E., Auta, J., Grayson, D. R., Matsumoto, K., Pappas, G. D., Zhang, X., & Guidotti, A. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00199-5 · Cited by 63 · see citing works
Self-citation
Pharmacologic effects and abuse liability of bretazenil, diazepam, and alprazolam in humans
Busto, U. E., Kaplan, H. L., Zawertailo, L. A., & Sellers, E. M. (1994) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1994.55 · Cited by 58 · see citing works
Immunohistochemical and immunoblot study of GABAA α1 and β2/3 subunits in the prefrontal cortex of subjects with schizophrenia and bipolar disorder
Ishikawa, M., Mizukami, K., Iwakiri, M., Hidaka, S., & Asada, T. (2004) · Neuroscience Research · doi:10.1016/j.neures.2004.06.006 · Cited by 51 · see citing works
Imidazenil, a partial positive allosteric modulator of GABAA receptors, exhibits low tolerance and dependence liabilities in the rat.
Auta, J., Giusti, P., Guidotti, A., & Costa, E. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22535-6 · Cited by 49 · see citing works
Self-citation
GABAergic Cortical Neuron Chromatin as a Putative Target to Treat Schizophrenia Vulnerability
Costa, E., Grayson, D. R., Mitchell, C. P., Tremolizzo, L., Veldić, M., & Guidotti, A. (2003) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v15.i2.20 · Cited by 47 · see citing works
Self-citation
Reversible Modification of GABA A Receptor Subunit mRNA Expression During Tolerance to Diazepam-induced Cognition Dysfunction
Longone, P., Impagnatiello, F., Guidotti, A., & Costa, E. (1996) · Neuropharmacology · doi:10.1016/s0028-3908(96)00071-8 · Cited by 46 · see citing works
Self-citation
HALLUCINATIONS AFTER WITHDRAWAL OF BACLOFEN
Lees, A. J., Clarke, C. R. A., & Harrison, M. J. G. (1977) · The Lancet · doi:10.1016/s0140-6736(77)92809-4 · Cited by 42 · see citing works
In Patas monkey, glutamic acid decarboxylase‐67 and reelin mRNA coexpression varies in a manner dependent on layers and cortical areas
Rodriguez, M. A., Caruncho, H. J., Costa, E., Pesold, C., Liu, W., & Guidotti, A. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10341 · Cited by 42 · see citing works
Self-citation
A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann’s Area 9 from subjects with bipolar disorder
Dean, B., Pavey, G., McLeod, M. C., Opeskin, K., Keks, N. A., & Copolov, D. (2001) · Journal of Affective Disorders · doi:10.1016/s0165-0327(00)00294-9 · Cited by 40 · see citing works
The Molecular Architecture of GABAA Receptors
Barnard, E. A. (2001) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-56833-6_2 · Cited by 36 · see citing works
Activation of corticostriatal pathway leads to similar morphological changes observed following haloperidol treatment
Meshul, C. K., Buckman, J. F., Allen, C., Riggan, J. P., & Feller, D. J. (1996) · Synapse · doi:10.1002/(sici)1098-2396(199604)22:4 · Cited by 30 · see citing works
Comparison of the effects of full and partial allosteric modulators of GABAA receptors on complex behavioral processes in monkeys
Auta, J., Faust, W. B., Lambert, P. M., Guidotti, A., Costa, E., & Moerschbaecher, J. M. (1995) · Behavioural Pharmacology · doi:10.1097/00008877-199506000-00003 · Cited by 28 · see citing works
Self-citation
Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine-induced cognition deficit in monkeys.
Thompson, D. M., Auta, J., Guidotti, A., & Costa, E. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09636-3 · Cited by 25 · see citing works
Self-citation
Imidazenil: a potent and safe protective agent against diisopropyl fluorophosphate toxicity
Auta, J., Costa, E., Davis, J. M., & Guidotti, A. (2003) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.09.010 · Cited by 21 · see citing works
Self-citation
Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance
Auta, J., Guidotti, A., & Costa, E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.5.2314 · Cited by 20 · see citing works
Self-citation
Blocking Plasticity in the Visual Cortex
Ferster, D. (2004) · Science · doi:10.1126/science.1096224 · Cited by 18 · see citing works
PARTIAL BENZODIAZEPINE AGONISTS IN SCHIZOPHRENIA: EXPECTATIONS AND PRESENT CLINICAL FINDINGS
Delini‐Stula, A., Berdah-Tordjman, D., & Neumann, N.-U. (1992) · Clinical Neuropharmacology · doi:10.1097/00002826-199201001-00211 · Cited by 17 · see citing works
Tolerance and Dependence to Ligands of the Benzodiazepine Recognition Sites Expressed by GABAA Receptors
Costa, E., Auta, J., & Guidotti, A. (2001) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-56833-6_8 · Cited by 16 · see citing works
Self-citation
HALLUCINATIONS AND BACLOFEN
Skausig, O. B., & Korsgaard, S. (1977) · The Lancet · doi:10.1016/s0140-6736(77)92463-1 · Cited by 16 · see citing works
Neuropharmacological evidence for an interaction between the GABA uptake inhibitor Cl‐966 and anxiolytic benzodiazepines
Giusti, P., Guidotti, A., Danysz, W., Auta, J., & Costa, E. (1990) · Drug Development Research · doi:10.1002/ddr.430210307 · Cited by 13 · see citing works
Self-citation
Structural Abnormalities of Subicular Dendrites in Subjects With Schizophrenia and Mood Disorders: Preliminary Findings
Rosoklija, G., Toomayan, G., Ellis, S. P., Keilp, J., Mann, J. J., Latov, N., Hays, A. P., & Dwork, A. J. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.4.349 · Cited by 1 · see citing works
Untitled work
Wang (1997) · doi:10.1002/(sici)1098-2396(199709)27:1

Flagged first, then by citations

Sorted by citations

Animal models of schizophrenia
Jones, C., Watson, D., & Fone, K. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01386.x · Cited by 771 · see citing works
Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes
Rudolph, U., & Knoflach, F. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3502 · Cited by 733 · see citing works
Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression
Choudary, P. V., Molnar, M., Evans, S. J., Tomita, H., Li, J., Vawter, M. P., Myers, R., Bunney, W. E., Akil, H., Watson, S. J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507901102 · Cited by 653 · see citing works
Current Concepts and Treatments of Schizophrenia
Stępnicki, P., Kondej, M., & Kaczor, A. A. (2018) · Molecules · doi:10.3390/molecules23082087 · Cited by 570 · see citing works
Reelin promoter hypermethylation in schizophrenia
Grayson, D. R., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C. P., Guidotti, A., & Costa, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503736102 · Cited by 553 · see citing works
Self-citation
GABAergic interneuron origin of schizophrenia pathophysiology
Nakazawa, K., Zsiros, V., Jiang, Z., Nakao, K., Kolata, S., Zhang, S., & Belforte, J. E. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.022 · Cited by 498 · see citing works
Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders
Akbarian, S., & Huang, H. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2006.04.001 · Cited by 362 · see citing works
Review: Glutamate and dopamine dysregulation in schizophrenia — a synthesis and selective review
Stone, J., Morrison, P., & Pilowsky, L. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881106073126 · Cited by 392 · see citing works
Epigenetic basis of mental illness
Nestler, E. J., Peña, C. J., Kundakovic, M., Mitchell, A., & Akbarian, S. (2016) · The Neuroscientist · doi:10.1177/1073858415608147 · Cited by 342 · see citing works
GABA A Receptor Subtypes: Therapeutic Potential in Down Syndrome, Affective Disorders, Schizophrenia, and Autism
Rudolph, U., & Möhler, H. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-135947 · Cited by 319 · see citing works
Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression
Klempan, T. A., Sequeira, A., Canetti, L., Lalovic, A., Ernst, C., ffrench-Mullen, J., & Turecki, G. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002110 · Cited by 294 · see citing works
Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation
Dong, E., Nelson, M., Grayson, D. R., Costa, E., & Guidotti, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805493105 · Cited by 284 · see citing works
Self-citation
Gamma synchrony: towards a translational biomarker for the treatment-resistant symptoms of schizophrenia.
Gandal, M. J., Edgar, J. C., Klook, K., & Siegel, S. J. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.02.007 · Cited by 269 · see citing works
Epigenetic modifications of GABAergic interneurons are associated with the schizophrenia-like phenotype induced by prenatal stress in mice
Matrisciano, F., Tueting, P., Dalal, I., Kadriu, B., Grayson, D. R., Davis, J. M., Nicoletti, F., & Guidotti, A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.04.013 · Cited by 271 · see citing works
Self-citation
The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders
Grayson, D. R., & Guidotti, A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.125 · Cited by 267 · see citing works
Self-citation
Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake
Pinna, G., Costa, E., & Guidotti, A. (2006) · Psychopharmacology · doi:10.1007/s00213-005-0213-2 · Cited by 245 · see citing works
Self-citation
Evidence for the Risks and Consequences of Adolescent Cannabis Exposure
Levine, A., Clemenza, K., Rynn, M., & Lieberman, J. (2017) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2016.12.014 · Cited by 239 · see citing works
Past and Present Progress in the Pharmacologic Treatment of Schizophrenia
Kane, J. M., & Correll, C. U. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.10r06264yel · Cited by 232 · see citing works
The benzamide MS-275 is a potent, long-lasting brain region-selective inhibitor of histone deacetylases
Simonini, M. V., Camargo, L. M., Dong, E., Maloku, E., Veldić, M., Costa, E., & Guidotti, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510341103 · Cited by 229 · see citing works
Self-citation
Antipsychotic Drugs: Comparison in Animal Models of Efficacy, Neurotransmitter Regulation, and Neuroprotection
Lieberman, J. A., Bymaster, F. P., Meltzer, H. Y., Deutch, A. Y., Duncan, G. E., Marx, C. E., Aprille, J. R., Dwyer, D. S., Li, X., Mahadik, S. P., et al. (2008) · Pharmacological Reviews · doi:10.1124/pr.107.00107 · Cited by 223 · see citing works
Epigenetic GABAergic targets in schizophrenia and bipolar disorder
Guidotti, A., Auta, J., Chen, Y., Davis, J. M., Dong, E., Gavin, D. P., Grayson, D. R., Matrisciano, F., Pinna, G., Satta, R., et al. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.10.021 · Cited by 220 · see citing works
Self-citation
Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease
Govindpani, K., Calvo-Flores Guzmán, B., Vinnakota, C., Waldvogel, H., Faull, R., & Kwakowsky, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18081813 · Cited by 208 · see citing works
Cognitive disruption and altered hippocampus synaptic function in Reelin haploinsufficient mice
QIU, S., KORWEK, K., PRATTDAVIS, A., PETERS, M., BERGMAN, M., & WEEBER, E. (2006) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.11.001 · Cited by 202 · see citing works
Nicotine decreases DNA methyltransferase 1 expression and glutamic acid decarboxylase 67 promoter methylation in GABAergic interneurons
Satta, R., Maloku, E., Zhubi, A., Pibiri, F., Hajós, M., Costa, E., & Guidotti, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808699105 · Cited by 202 · see citing works
Self-citation
Reelin and glutamic acid decarboxylase 67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia
Dong, E., Agís‐Balboa, R. C., Simonini, M. V., Grayson, D. R., Costa, E., & Guidotti, A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505394102 · Cited by 198 · see citing works
Self-citation
Proof-of-concept trial with the neurosteroid pregnenolone targeting cognitive and negative symptoms in schizophrenia
Marx, C. E., Keefe, R. S. E., Buchanan, R. W., Hamer, R. M., Kilts, J. D., Bradford, D. W., Strauss, J. L., Naylor, J. C., Payne, V. M., Lieberman, J. A., et al. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.26 · Cited by 193 · see citing works
Wnt Signaling: Role in Alzheimer Disease and Schizophrenia
Inestrosa, N. C., Montecinos-Oliva, C., & Fuenzalida, M. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9417-5 · Cited by 186 · see citing works
Selective epigenetic alteration of layer I GABAergic neurons isolated from prefrontal cortex of schizophrenia patients using laser-assisted microdissection
Ruzicka, W. B., Zhubi, A., Veldić, M., Grayson, D. R., Costa, E., & Guidotti, A. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001954 · Cited by 186 · see citing works
Self-citation
GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies
de Jonge, J. C., Vinkers, C. H., Pol, H. E. H., & Marsman, A. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00118 · Cited by 185 · see citing works
Prefrontal GABAA receptor α-subunit expression in normal postnatal human development and schizophrenia
Duncan, C. E., Webster, M. J., Rothmond, D. A., Bahn, S., Elashoff, M., & Shannon Weickert, C. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.12.007 · Cited by 169 · see citing works
DNA Methyltransferase Inhibitors Coordinately Induce Expression of the Human Reelin and Glutamic Acid Decarboxylase 67 Genes
Kundaković, M., Chen, Y., Costa, E., & Grayson, D. R. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.030635 · Cited by 168 · see citing works
Self-citation
Proteomic analysis of membrane microdomain-associated proteins in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder reveals alterations in LAMP, STXBP1 and BASP1 protein expression
Behan, Á. T., Byrne, C., Dunn, M. J., Cagney, G., & Cotter, D. (2008) · Molecular Psychiatry · doi:10.1038/mp.2008.7 · Cited by 166 · see citing works
Genetic associations with schizophrenia: Meta-analyses of 12 candidate genes
Shi, J., Gershon, E. S., & Liu, C. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.06.016 · Cited by 159 · see citing works
Role of GABAB receptors in learning and memory and neurological disorders
Heaney, C. F., & Kinney, J. W. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.01.007 · Cited by 154 · see citing works
Epigenetic mechanisms expressed in basal ganglia GABAergic neurons differentiate schizophrenia from bipolar disorder
Veldić, M., Kadriu, B., Maloku, E., Agís‐Balboa, R. C., Guidotti, A., Davis, J. M., & Costa, E. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2006.11.029 · Cited by 150 · see citing works
Self-citation
The Reelin and GAD67 Promoters Are Activated by Epigenetic Drugs That Facilitate the Disruption of Local Repressor Complexes
Kundaković, M., Chen, Y., Guidotti, A., & Grayson, D. R. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.051763 · Cited by 149 · see citing works
Self-citation
Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models
O'Donnell, P. (2011) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr028 · Cited by 145 · see citing works
Pregnenolone as a novel therapeutic candidate in schizophrenia: emerging preclinical and clinical evidence
Marx, C. E., Bradford, D. W., Hamer, R. M., Naylor, J. C., Allen, T. B., Lieberman, J. A., Strauss, J. L., & Kilts, J. D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.06.076 · Cited by 138 · see citing works
The human reelin gene: Transcription factors (+), repressors (−) and the methylation switch (+/−) in schizophrenia
Grayson, D. R., Chen, Y., Costa, E., Dong, E., Guidotti, A., Kundaković, M., & Sharma, R. P. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.01.007 · Cited by 139 · see citing works
Self-citation
Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders
Tang, B., Dean, B., & Thomas, E. A. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.61 · Cited by 137 · see citing works
An upregulation of DNA-methyltransferase 1 and 3a expressed in telencephalic GABAergic neurons of schizophrenia patients is also detected in peripheral blood lymphocytes
Zhubi, A., Veldić, M., Puri, N. V., Kadriu, B., Caruncho, H. J., Loza, I. B., Sershen, H. W., Lajtha, Á., Smith, R. C., Guidotti, A., et al. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.03.020 · Cited by 129 · see citing works
Self-citation
Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling
Guidotti, A., Dong, E., Kundakovic, M., Satta, R., Grayson, D. R., & Costa, E. (2009) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2008.10.010 · Cited by 130 · see citing works
Self-citation
Drug targets for cognitive enhancement in neuropsychiatric disorders.
Wallace, T. L., Ballard, T. M., Pouzet, B., Riedel, W. J., & Wettstein, J. G. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.03.022 · Cited by 127 · see citing works
Functional regulation of GABAA receptors in nervous system pathologies
Hines, R. M., Davies, P. A., Moss, S. J., & Maguire, J. L. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.10.007 · Cited by 125 · see citing works
GABA abnormalities in schizophrenia: A methodological review of in vivo studies
Taylor, S. F., & Tso, I. F. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.10.011 · Cited by 125 · see citing works
Histone modifications, DNA methylation, and Schizophrenia
Gavin, D. P., & Sharma, R. P. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.10.010 · Cited by 121 · see citing works
Effects of γ-Aminobutyric Acid–Modulating Drugs on Working Memory and Brain Function in Patients With Schizophrenia
Menzies, L., Ooi, C., Kamath, S., Suckling, J., McKenna, P., Fletcher, P., Bullmore, E., & Stephenson, C. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.2.156 · Cited by 120 · see citing works
Reelin in the years: controlling neuronal migration and maturation in the mammalian brain
D'Arcangelo, G. (2014) · Advances in Neuroscience · doi:10.1155/2014/597395 · Cited by 120 · see citing works
In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders
Pantazopoulos, H., & Berretta, S. (2015) · Neural Plasticity · doi:10.1155/2016/9847696 · Cited by 118 · see citing works
GABAAreceptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: Possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders
Matsumoto, K., Puia, G., Dong, E., & Pinna, G. (2007) · Stress · doi:10.1080/10253890701200997 · Cited by 117 · see citing works
Self-citation
GABA concentration in schizophrenia patients and the effects of antipsychotic medication: A proton magnetic resonance spectroscopy study
Tayoshi, S., Nakataki, M., Sumitani, S., Taniguchi, K., Shibuya‐Tayoshi, S., Numata, S., Iga, J., Ueno, S., Harada, M., & Ohmori, T. (2009) · Schizophrenia Research · doi:10.1016/j.schres.2009.11.011 · Cited by 113 · see citing works
The rise of a new GABA pharmacology
Möhler, H. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.10.020 · Cited by 111 · see citing works
Pharmacological activation of group-ii metabotropic glutamate receptors corrects a schizophrenia-like phenotype induced by prenatal stress in mice
Matrisciano, F., Tueting, P., Maccari, S., Nicoletti, F., & Guidotti, A. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.274 · Cited by 110 · see citing works
Self-citation
Theranostic Biomarkers for Schizophrenia
Perković, M. N., Erjavec, G. N., Štrac, D. Š., Uzun, S., Kozumplik, O., & Pivac, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040733 · Cited by 97 · see citing works
Blockade of alcohol's amnestic activity in humans by an α5 subtype benzodiazepine receptor inverse agonist
Nutt, D., Besson, M. J., Wilson, S. J., Dawson, G. R., & Lingford-Hughes, A. R. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.08.008 · Cited by 109 · see citing works
Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition
Bast, T., Pezze, M. A., & McGarrity, S. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13850 · Cited by 92 · see citing works
Do NMDA receptor antagonist models of schizophrenia predict the clinical efficacy of antipsychotic drugs?
Large, C. H. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107077712 · Cited by 94 · see citing works
A stereological comparison of GAD67 and reelin expression in the hippocampal stratum oriens of offspring from two mouse models of maternal inflammation during pregnancy
Harvey, L., & Boksa, P. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.11.022 · Cited by 92 · see citing works
Dysregulation of GABAergic Neurotransmission in Mood Disorders
Bielau, H., Steiner, J. H., Mawrin, C., Trübner, K., Brisch, R., Meyer-Lotz, G., Brodhun, M., Dobrowolny, H., Baumann, B., Gos, T., et al. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1397.081 · Cited by 90 · see citing works
Epigenetic mechanisms in schizophrenia
Akbarian, S. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/sakbarian · Cited by 89 · see citing works
Reelin down-regulation in mice and psychosis endophenotypes
Tueting, P. A., Doueiri, M.-S., Guidotti, A., DAVIS, J., & Costa, E. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.04.001 · Cited by 88 · see citing works
Self-citation
Genomic imprinting in the development and evolution of psychotic spectrum conditions
Crespi, B. J. (2008) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2008.00050.x · Cited by 86 · see citing works
Evidence for disease and antipsychotic medication effects in post-mortem brain from schizophrenia patients
Chan, M. K., Tsang, T. M., Harris, L. W., Guest, P. C., Holmes, E. C., & Bahn, S. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.100 · Cited by 85 · see citing works
A Comprehensive Optogenetic Pharmacology Toolkit for In Vivo Control of GABA A Receptors and Synaptic Inhibition
Lin, W.-C., Tsai, M., Davenport, C. M., Smith, C. M., Veit, J., Wilson, N. M., Adesnik, H., & Krämer, R. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.026 · Cited by 82 · see citing works
Ziziphus spinosa seeds for insomnia: A review of chemistry and psychopharmacology
Shergis, J. L., Ni, X., Sarris, J. J., Zhang, A. L., Guo, X., Xue, C. C., Lu, C., & Hügel, H. (2017) · Phytomedicine · doi:10.1016/j.phymed.2017.07.004 · Cited by 82 · see citing works
HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia‐like animals
Večeřa, J., Bártová, E., Krejčí, J., Legartová, S., Komůrková, D., Kučerová, J., Štark, T., Dražanová, E., Kašpárek, T., Šulcová, A., et al. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25914 · Cited by 80 · see citing works
Behavioral and molecular neuroepigenetic alterations in prenatally stressed mice: relevance for the study of chromatin remodeling properties of antipsychotic drugs
Dong, E., Tueting, P. A., Matrisciano, F., Grayson, D. R., & Guidotti, A. (2016) · Translational Psychiatry · doi:10.1038/tp.2015.191 · Cited by 80 · see citing works
Self-citation
Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation
Pinna, G., Agís‐Balboa, R. C., Zhubi, A., Matsumoto, K., Grayson, D. R., Costa, E., & Guidotti, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600329103 · Cited by 79 · see citing works
Self-citation
Effects on the expression of GABAA receptor subunits by jujuboside A treatment in rat hippocampal neurons
You, Z., Xia, Q., Liang, F., Tang, Y., Xu, C.-L., Huang, J. H., Zhao, L., Zhang, W., & He, J.-J. (2010) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2010.01.034 · Cited by 76 · see citing works
DNA methylation and demethylation as targets for antipsychotic therapy
Guidotti, A., & Grayson, D. R. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/aguidotti · Cited by 72 · see citing works
Self-citation
Increased water diffusivity in the frontal and temporal cortices of schizophrenic patients
Shin, Y., Kwon, J. S., Ha, T. H., Park, H., Kim, D. J., Hong, S., Moon, W., Lee, J. M., Kim, I. Y., Kim, S. I., et al. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.11.017 · Cited by 68 · see citing works
The Fragile Brain: Stress Vulnerability, Negative Affect and GABAergic Neurocircuits in Psychosis
Taylor, S. F., Grove, T. B., Ellingrod, V. L., & Tso, I. F. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sbz046 · Cited by 67 · see citing works
An Updated Unified Pharmacophore Model of the Benzodiazepine Binding Site on γ-Aminobutyric Acida Receptors: Correlation with Comparative Models
Clayton, T., Chen, J., Ernst, M. C., Richter, L., Cromer, B. A., Morton, C. J., Ng, H. H., Kaczorowski, C. C., Helmstetter, F. J., Furtmüller, R., et al. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707782360097 · Cited by 66 · see citing works
Schizophrenia: Treatment Targets Beyond Monoamine Systems
Ibrahim, H. M., & Tamminga, C. A. (2011) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105851 · Cited by 62 · see citing works
The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia
Uliana, D. L., Lisboa, J. R., Gomes, F. V., & Grace, A. A. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116298 · Cited by 65 · see citing works
Amphetamine sensitization in rats as an animal model of schizophrenia.
Peleg-Raibstein, D., Knuesel, I., & Feldon, J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.037 · Cited by 69 · see citing works
GABAergic promoter hypermethylation as a model to study the neurochemistry of schizophrenia vulnerability
Costa, E., Chen, Y., Dong, E., Grayson, D. R., Kundaković, M., Maloku, E., Ruzicka, W. B., Satta, R., Veldić, M., Zhubi, A., et al. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.9.1.87 · Cited by 62 · see citing works
Self-citation
Common Variants on Xq28 Conferring Risk of Schizophrenia in Han Chinese
Wong, E., So, H., Li, M., Wang, Q., Butler, A. W., Paul, B., Wu, H.-M., Hui, T. C. K., Choi, S.-C., So, M., et al. (2013) · Schizophrenia Bulletin · doi:10.1093/schbul/sbt104 · Cited by 61 · see citing works
In vivo gamma-aminobutyric acid and glutamate levels in people with first-episode schizophrenia: A proton magnetic resonance spectroscopy study
Chiu, P. W., Lui, S. S. Y., Hung, K. S. Y., Chan, R. C. K., Chan, Q., Sham, P. C., Cheung, E. F. C., & Mak, H. K. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.07.021 · Cited by 60 · see citing works
Validation and pharmacological characterisation of MK-801-induced locomotor hyperactivity in BALB/C mice as an assay for detection of novel antipsychotics
Bradford, A. M., Savage, K. M., Jones, D. N. C., & Kalinichev, M. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1938-0 · Cited by 59 · see citing works
Altered cortico‐striatal synaptic plasticity and related behavioural impairments in reeler mice
Marrone, M. C., Marinelli, S., Biamonte, F., Keller, F., Sgobio, C., Ammassari‐Teule, M., Bernardi, G., & Mercuri, N. B. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05083.x · Cited by 58 · see citing works
Regulation of synaptic plasticity in a schizophrenia model
Gisabella, B., Bolshakov, V. Y., & Benes, F. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506034102 · Cited by 55 · see citing works
Toward the Identification of Peripheral Epigenetic Biomarkers of Schizophrenia
Guidotti, A., Auta, J., Davis, J. M., Dong, E., Gavin, D. P., Grayson, D. R., Sharma, R. P., Smith, R. C., Tueting, P. A., & Zhubi, A. (2014) · Journal of Neurogenetics · doi:10.3109/01677063.2014.892485 · Cited by 54 · see citing works
Self-citation
Clozapine and GABA transmission in schizophrenia disease models: establishing principles to guide treatments.
O'Connor, W., & O'Shea, S. (2015) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2015.01.005 · Cited by 54 · see citing works
Oscillatory, computational, and behavioral evidence for impaired gabaergic inhibition in schizophrenia
Shaw, A. D., Knight, L., Freeman, T. C. A., Williams, G. M., Moran, R. J., Friston, K. J., Walters, J. T. R., & Singh, K. D. (2019) · Schizophrenia Bulletin · doi:10.1093/schbul/sbz066 · Cited by 54 · see citing works
DNA methyltransferases1 (DNMT1) and 3a (DNMT3a) colocalize with GAD67‐positive neurons in the GAD67‐GFP mouse brain
Kadriu, B., Guidotti, A., Chen, Y., & Grayson, D. R. (2011) · The Journal of Comparative Neurology · doi:10.1002/cne.23020 · Cited by 53 · see citing works
Self-citation
GABAA/Benzodiazepine receptor binding in patients with schizophrenia using [11C]Ro15-4513, a radioligand with relatively high affinity for α5 subunit
Asai, Y., Takano, A., Ito, H., Okubo, Y., Matsuura, M., Otsuka, A., Takahashi, H., Ando, T., Ito, S., Arakawa, R., et al. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.10.014 · Cited by 53 · see citing works
Epigenetic dysregulation in schizophrenia: molecular and clinical aspects of histone deacetylase inhibitors
Hasan, A., Mitchell, A., Schneider, A., Halene, T. B., & Akbarian, S. (2013) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-013-0395-2 · Cited by 51 · see citing works
Neurological dysfunctions associated with altered BACE 1‐dependent Neuregulin‐1 signaling
Hu, X., Fan, Q., Hou, H., & Yan, R. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13395 · Cited by 52 · see citing works
Pathophysiological power of improper tonic GABAA conductances in mature and immature models
Egawa, K., & Fukuda, A. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00170 · Cited by 54 · see citing works
Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-Immunoreactive neuropil
Gos, T., Günther, K., Bielau, H., Dobrowolny, H., Mawrin, C., Trübner, K., Brisch, R., Steiner, J. H., Bernstein, H., Jankowski, Z., et al. (2008) · Journal of Affective Disorders · doi:10.1016/j.jad.2008.04.021 · Cited by 48 · see citing works
Isolation rearing-induced reduction of brain 5α-reductase expression: Relevance to dopaminergic impairments
Bortolato, M., Devoto, P., Roncada, P., Frau, R., Flore, G., Saba, P., Pistritto, G., Soggiù, A., Pisanu, S., Zappalà, A., et al. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.013 · Cited by 48 · see citing works
GABRB2 Association with Schizophrenia: Commonalities and Differences Between Ethnic Groups and Clinical Subtypes
Lo, W.-S., Harano, M., Gawlik, M., Yu, Z., Chen, J., Pun, F. W., Tong, K.-L., Zhao, C., Ng, S.-K., Tsang, S., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.003 · Cited by 47 · see citing works
A methylome-wide mQTL analysis reveals associations of methylation sites with GAD1 and HDAC3 SNPs and a general psychiatric risk score
Ciuculete, D. M., Boström, A. E., Voisin, S., Philipps, H., Titova, O. E., Bandstein, M., Nikontovic, L., Williams, M. J., Mwinyi, J., & Schiöth, H. B. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.275 · Cited by 40 · see citing works
Dopamine Modulation of Prefrontal Cortex Interneurons Occurs Independently of DARPP-32
Trantham‐Davidson, H., Kröner, S., & Seamans, J. K. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm133 · Cited by 46 · see citing works
Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients
Suzuki, K., Nakamura, K., Iwata, Y., Sekine, Y., Kawai, M., Sugihara, G., Tsuchiya, K. J., Suda, S., Matsuzaki, H., Takei, N., et al. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2007.09.029 · Cited by 45 · see citing works
Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls
Zhang, R., Zhang, T., Ali, A. M., Washih, M. A., Pickard, B. S., & Watson, D. G. (2016) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2016.02.003 · Cited by 43 · see citing works
Hippocampal α5 subunit-containing GABAA receptors are involved in the development of the latent inhibition effect
Gerdjikov, T. V., Rudolph, U., Keist, R., Möhler, H., Feldon, J., & Yee, B. K. (2008) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.06.003 · Cited by 43 · see citing works
Multiple roles of Sonic Hedgehog in the developing human cortex are suggested by its widespread distribution
Memi, F., Zečević, N., & Radonjić, N. V. (2018) · Brain Structure and Function · doi:10.1007/s00429-018-1621-5 · Cited by 44 · see citing works
Analysis of the GAD1 promoter: trans-acting factors and DNA methylation converge on the 5' untranslated region.
Chen, Y., Dong, E., & Grayson, D. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.09.017 · Cited by 42 · see citing works
Self-citation

Neurosciences in the Third Millennium: A Tribute to Mimo Costa
Murray, T. F. (2004) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v16.i12.10 · Cited by 111 · see citing works
Dendritic Spine Hypoplasticity and Downregulation of Reelin and GABAergic Tone in Schizophrenia Vulnerability
Costa, E., Davis, J. M., Grayson, D. R., Guidotti, A., Pappas, G. D., & Pesold, C. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0436 · Cited by 197 · see citing works
Self-citation
t p r u
Guidotti, R., Dong, E., Marija, K., & Costa, E. (2015)
Self-citation
Epigenetic Regulation of GABAergic Targets in Psychiatry
Grayson, D. R., Kundaković, M., Chen, Y., Dong, E., & Guidotti, A. (2011) · Springer eBooks · doi:10.1007/978-3-642-17426-1_2 · Cited by 2 · see citing works
Self-citation
Alterations in neuromodulators of GABAergic transmission in the cerebellar cortex of patients with schizophrenia.
Bullock, W. M. (2010) · UNM’s Digital Repository (University of New Mexico)

Authors: Guidotti, A., Auta, J., Davis, J. M., Dong, E., Grayson, D. R., Veldic, M., Zhang, X., & Costa, E.
Affiliations: University of Illinois Chicago (US)
Corresponding author: Costa, Erminio
ORCID: Guidotti, Alessandro
Auta, James
Davis, John M.
Dong, Erbo
Grayson, Dennis R.
Zhang, Xianquan
Venue: Psychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2005-04-28
Volume: 180
Issue: 2
Pages: 191-205
ISSN: 0033-3158 (ISSN-L)
1432-2072
DOI: 10.1007/s00213-005-2212-8
OpenAlex: W2072551779
Cited by: 262
References: 104
Citations by year: 2026: 1 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 11 · 2019: 7 · 2018: 12 · 2017: 10 · 2016: 11 · 2015: 16 · 2014: 22 · 2013: 13 · 2012: 10
FWCI: 2.92
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (R01MH6262A, R01MH062188, R01MH062090, R01MH62188, R01MH62090)
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, bipolar disorder, GABAergic dysfunction, GABAergic interneurons, reelin, GAD67, prefrontal cortex, benzodiazepines, positive allosteric modulation, GABAA receptor, alpha1 subunit, diazepam, sedation, drug tolerance, antipsychotic drugs, dendritic spine plasticity
MeSH terms: Reelin Protein, Animals, Benzodiazepines, Bipolar Disorder, Cerebral Cortex, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Humans, Nerve Tissue Proteins, Synaptic Transmission, Receptors, GABA-A, Schizophrenia, Serine Endopeptidases, Cell Adhesion Molecules, Neuronal, Extracellular Matrix Proteins, Chloride Channels

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

GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks