title: 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.
authors.affiliation: Division of Child & Adolescent Psychiatry, Johns Hopkins University School of Medicine, 1800 Orleans St.-12th floor, Baltimore, MD, 21287, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Grados
authors.forename: Hyung Mo
authors.initials: HM
authors.lastname: Sung
authors.forename: Sejin
authors.initials: S
authors.lastname: Kim
authors.forename: Siddharth
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D053263:Gene Regulatory Networks; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D058570:TOR Serine-Threonine Kinases
keywords: FKBP12; GRM5; brain-derived neutrophic factor (BDNF); mammalian target of rapamycin (mTOR); obsessive-compulsive disorder (OCD)