GABA and schizophrenia: a review of basic science and clinical studies.
BACKGROUND
A converging body of evidence implicates the gamma-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.
Wassef
Adel
A
University of Texas Health Sciences Center, Room 2C-07, Houston-Harris County Psychiatric Center, 2800 South MacGregor Way, Houston, TX 77021, USA. awassef@mind.hcpc.uth.tmc.edu
Baker
Jeffrey
J
Kochan
Lisa D
LD
D000818:Animals; D002986:Clinical Trials as Topic; D018682:GABA Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011963:Receptors, GABA-A / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018682:GABA Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid