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

Drug Dev Res. 2014 Sep;75(6):372-83. doi: 10.1002/ddr.21223.

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.

Keywords: FKBP12; GRM5; brain-derived neutrophic factor (BDNF); mammalian target of rapamycin (mTOR); obsessive-compulsive disorder (OCD).

Publication types

  • Review

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Central Nervous System / metabolism
  • Drug Discovery / methods
  • Gene Regulatory Networks
  • Glutamic Acid / metabolism*
  • Humans
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / metabolism*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Glutamic Acid
  • TOR Serine-Threonine Kinases