GABAergic mechanisms of hippocampal hyperactivity in schizophrenia

Schizophrenia is associated with abnormalities of hippocampal structure and function. Neuroimaging studies have shown that the hippocampus is hyperactive in schizophrenia. Here we explore GABAergic mechanisms of this hippocampal hyperactivity. The initial evidence for GABAergic abnormalities of the hippocampus in schizophrenia came from post-mortem studies of interneuron number, protein expression, and gene expression. These studies revealed marked decreases in gene and protein expression of somatostatin-positive and parvalbumin-positive interneurons, and indicated reduced interneuron numbers. Animal studies of decreased parvalbumin and NMDA-receptor function have shown that selective abnormalities of hippocampal interneurons mimic some of the cognitive deficits and clinical features of schizophrenia. The post-mortem and animal studies are consistent with the neuroimaging finding of increased hippocampal activity in schizophrenia, which can explain some of the psychotic symptoms and cognitive deficits. Taken together, these findings may guide the development of biomarkers and the development of new treatments for psychosis.