GABAA and GABAB receptor dysregulation in superior frontal cortex of subjects with schizophrenia and bipolar disorder

S H Fatemi, Timothy D. Folsom, Paul D. Thuras

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Schizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma-aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAA and two GABAB receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls. Analyses of Variance (ANOVAs) identified significant group effects for protein levels for the α1, α6, β1, β3, δ, ɛ, and π GABAA receptor subunits and R1 and R2 GABAB receptor subunits. Follow-up t tests confirmed changes for these subunits in subjects with schizophrenia, subjects with bipolar disorder, or both groups. Alterations in stoichiometry of GABA receptor subunits could result in altered ligand binding, transmission, and pharmacology of GABA receptors in superior frontal cortex. Thus, impaired GABAergic transmission may negatively contribute to symptoms such as anxiety or panic as well as impaired learning and information processing, all of which are disrupted in schizophrenia and bipolar disorder. Taken together, these results provide additional evidence of GABAergic receptor abnormalities in these disorders.

Original languageEnglish (US)
Article numbere21973
Issue number7
StatePublished - Jul 2017

Bibliographical note

Funding Information:
Grant support by the National Institutes of Mental Health (Grant #1R01MH086000-01A2), and the Ewald Bipolar Disease Research Fund to SHF is gratefully acknowledged. S.H. Fatemi is also supported by the Bernstein Endowed Chair in Adult Psychiatry. Tissue samples from the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH068855 is gratefully acknowledged. The authors declare that there is no conflict of interest.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Copyright 2017 Elsevier B.V., All rights reserved.


  • GABRɛ
  • GABRα1
  • GABRα6
  • bipolar disorder
  • schizophrenia

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