Genetic Data Supporting the NMDA Glutamate Receptor Hypothesis for Schizophrenia

Thomas L. Schwartz, Shilpa Sachdeva, Stephen M. Stahl

doi:10.2174/138161212799958594

Abstract

The Dopamine Hypothesis has been the leading theory used to explain the mechanism of the clinical manifestation of schizophrenia symptoms for decades. It is unclear if excess dopaminergic activity is the primary pathophysiology causing psychosis or if this dopamine excess is triggered by upstream, downstream or neurodevelopmental abnormalities. A corollary hypothesis suggests that the glutamatergic system may be involved in the pathogenesis of schizophrenia, and that dysfunction of the glutamate system may actually lead to dopamine excess. The NMDA Receptor Hypofunction Hypothesis suggests that malfunctioning NMDA receptors may be the cause for the theoretically hypofunctioning glutamate system. This paper seeks to describe and discuss the potential underlying genetic vulnerabilities of the NMDA receptor and how aberrant genes coding for this receptor may lead to schizophrenia symptoms.

Keywords: NMDA receptor, schizophrenia, glutamate, genetics, Dopamine Hypothesis, neurodevelopmental abnormalities, ion channel, homeostasis, psychosis, psychiatric symptoms