Gene therapy for psychiatric disorders

Abstract

Gene therapy has become of increasing interest in clinical neurosurgery with the completion of numerous clinical trials for Parkinson disease, Alzheimer disease, and pediatric genetic disorders. With improved understanding of the dysfunctional circuitry mediating various psychiatric disorders, deep brain stimulation for refractory psychiatric diseases is being increasingly explored in human patients. These factors are likely to facilitate development of gene therapy for psychiatric diseases. Because delivery of gene therapy agents would require the same surgical techniques currently being employed for deep brain stimulation, neurosurgeons are likely to lead the development of this field, as has occurred in other areas of clinical gene therapy for neurologic disorders. We review the current state of gene therapy for psychiatric disorders and focus specifically on particular areas of promising research that may translate into human trials for depression, drug addiction, obsessive-compulsive disorder, and schizophrenia. Issues that are relatively unique to psychiatric gene therapy are also discussed.

Keywords: 5-HT; 5-Hydroxytryptamine; AAV; Addiction; Adeno-associated virus; Area 25; BDNF; Brain-derived neurotrophic factor; CNS; CPP; Central nervous system; Conditioned place preference; DISC1; Depression; Disrupted In Schizophrenia-1; FST; Forced swim test; Gene therapy; Infralimbic cortex; KO; Knockout; NAcc; Nucleus accumbens; OCD; Obsessive-compulsive disorder; PD; Parkinson disease; SRF; Serum response factor; Small interfering RNA; TST; Tail suspension test; p11; siRNA.