Glutamate theory in developing novel pharmacotherapies for obsessive compulsive disorder: Focusing on N-methyl-D-aspartate signaling

Obsessive compulsive disorder (OCD) is a prevalent and debilitating illness that often follows a chronic course. Up to 40% of OCD patients received little or no benefit from currently available pharmacotherapy or exposure-based behavior psychotherapy. Thus, there is an urgent need to develop new strategies for the treatment of OCD. Although the neurobiology and etiology of OCD are not completely understood, growing clinical and preclinical evidence appears to support the abnormalities of glutamatergic neurotransmission, including N-methyl-D-aspartate subtype receptor (NMDAR) function, in the pathophysiology and treatment of OCD. This review summarizes the findings from neuro imaging, candidate genes, animal models, and treatment studies in the context of glutamatergic dysregulation, with particular emphasis on the synaptic NMDAR function. The converging evidence indicates the potential of glutamate-modulating agents in the development of novel treatment for OCD.