Deciphering the disease process of schizophrenia: the contribution of cortical GABA neurons.

Schizophrenia is a devastating illness that is manifest through a variety of clinical signs and symptoms. Among these, impairments in certain critical cognitive functions, such as working memory, appear to represent the core features of the disorder. In this chapter, we review the evidence indicating that disturbances in neurotransmission by a subset of GABA neurons in the dorsolateral prefrontal cortex are commonly present in schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting pathophysiological process, alterations in the perisomatic inhibitory regulation of pyramidal neurons, underlies a reduced capacity for the synchronization of neuronal activity at gamma frequencies that is required for working memory function. We also discuss several pathogenetic mechanisms that could rise to the alterations in GABA neurotransmission and consider the implication of these findings for therapeutic interventions to improve cognitive function in individuals with schizophrenia.