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GABA and Schizophrenia: A Review of Basic Science and Clinical Studies

Wassef, Adel MD*; Baker, Jeffrey PhDdagger;; Kochan, Lisa D. PhDdagger;

Journal of Clinical Psychopharmacology: December 2003 - Volume 23 - Issue 6 - pp 601-640
Review Article

Background: A converging body of evidence implicates the γ-aminobutyric acid (GABA) neurotransmitter system in the pathogenesis of schizophrenia.

Methods: The authors review neuroscience literature and clinical studies investigating the role of the GABA system in the pathophysiology of schizophrenia. First, a background on the GABA system is provided, including GABA pharmacology and neuroanatomy of GABAergic neurons. Results from basic science schizophrenia animal models and human studies are reviewed. The role of GABA in cognitive dysfunction in schizophrenia is then presented, followed by a discussion of GABAergic compounds used in monotherapy or adjunctively in clinical schizophrenia studies.

Results: In basic studies, reductions in GABAergic neuronal density and abnormalities in receptors and reuptake sites have been identified in several cortical and subcortical GABA systems. A model has been developed suggesting GABA’s role (including GABA-dopamine interactions) in schizophrenia. In several clinical studies, the use of adjunctive GABA agonists was associated with greater improvement in core schizophrenia symptoms.

Conclusions: Alterations in the GABA neurotransmitter system are found in clinical and basic neuroscience schizophrenia studies as well as animal models and may be involved in the pathophysiology of schizophrenia. The interaction of GABA with other well-characterized neurotransmitter abnormalities remains to be understood. Future studies should elucidate the potential therapeutic role for GABA ligands in schizophrenia treatment.

In 1999, Wassef et al. reviewed the GABAergic compounds used in the treatment of schizophrenia, primarily focusing on valproate (valproic acid—VAP and its derivatives). 1 The current review provides an update on the clinical schizophrenia studies using GABAergic compounds and also reviews basic neuroscience studies relevant to the understanding of GABA’s role in the pathophysiology of schizophrenia. We begin with a review of the pharmacological role of GABA in normal brain functioning.

*University of Texas Health Sciences Center, Houston- Harris County Psychiatric Center, Houston, TX;

dagger;Abbott Laboratories, Abbott Park, IL;

March 9, 2003; accepted after revision August 15, 2003.

Address correspondence and reprint requests to Adel Wassef, MD, University of Texas Health Sciences, 2800 South MacGregor Way, Room 2C-07, HCPC, Houston, TX 77021; E-mail:

© 2003 Lippincott Williams & Wilkins, Inc.