Genetic findings in obsessive-compulsive disorder connect to brain-derived neutrophic factor and mammalian target of rapamycin pathways: implications for drug development.

ABSTRACT

Traditional pharmacological approaches to the treatment of obsessive-compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1-MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation and neurogenesis pathways BDNF-mTOR. These pathways are emerging as a promising area of research for the development of neuroprotective pharmaceuticals. Emergent genetic epidemiologic data on OCD and repetitive behaviors may support new approaches for pharmacological discovery. Neuroprotective approaches that take into consideration glutamate-mediated BDNF-mTOR pathways are suggested by OCD susceptibility genes.