The Role of GABAA Receptors in Schizophrenia

Schizophrenia is a neurodevelopmental disorder triggered by environmental factors in the pre-, perior postnatal periods and manifesting as changes in brain chemistry and morphology. A deficit in the GABAergic system is strongly implicated in schizophrenia, resulting in perturbed inhibitory transmission. GABAA receptors are altered in post-mortem brains of persons with schizophrenia. Increased binding to the orthosteric binding site and decreased binding to the benzodiazepine site have been observed in a number of brain regions, while α1 and α2 subunit expression is increased and γ2 subunit expression is decreased in the prefrontal cortex. While the cause of these changes is not known, it is evident that they may be due to an early life insult, such as infection or stress, which alters the maturational expression of GABAA receptors and thus the balance between inhibition and excitation in the developing brain. As GABAergic transmission is vital in modulating cortical activity, the altered receptor activity and pharmacology would disrupt normal neural processing, resulting in an imbalance in other systems, and symptoms of schizophrenia.