GABAA receptors and their associated proteins: Implications in the etiology and treatment of schizophrenia and related disorders

γ-aminobutyric acid type A (GABAA) receptors play an important role in mediating fast synaptic inhibition in the brain. They are ubiquitously expressed in the CNS and also represent a major site of action for clinically relevant drugs. Recent technological advances have greatly clarified the molecular and cellular roles played by distinct GABAA receptor subunit classes and isoforms in normal brain function. At the same time, postmortem and genetic studies have linked neuropsychiatric disorders including schizophrenia and bipolar disorder with GABAergic neurotransmission and various specific GABAA receptor subunits, while evidence implicating GABAAR-associated proteins is beginning to emerge. In this review we discuss the mounting genetic, molecular, and cellular evidence pointing toward a role for GABAA receptor heterogeneity in both schizophrenia etiology and therapeutic development. Finally, we speculate on the relationship between schizophrenia-related disorders and selected GABAA receptor associated proteins, key regulators of GABAA receptor trafficking, targeting, clustering, and anchoring that often carry out these functions in a subtype-specific manner.