Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements, applications, and future scope.

摘要: No specific gene has been identified for any major psychiatric disorder, including schizophrenia, in spite of strong evidence supporting a genetic basis these complex and devastating disorders. There are several likely reasons this failure, ranging from poor study design with low statistical power to mechanisms such as polygenic inheritance, epigenetic interactions, pleiotropy. Most designs currently use inadequate uncover mechanisms. However, date, studies have provided some valuable insight into the causes potential therapies is growing body suggesting that understanding etiology illnesses, will be more successful integrative approaches considering both factors. For example, genes those encoding dopamine receptors (DRD2, DRD3, DRD4), serotonin receptor 2A (HTR2A) catechol-O-methyltransferase (COMT) implicated schizophrenia related disorders through meta-analyses large, multicenter studies. also role DRD1, NMDA (GRIN1, GRIN2A, GRIN2B), brain-derived neurotrophic factor (BDNF), transporter (SLC6A3) bipolar disorder. Recent indicated modification reelin (RELN), BDNF, DRD2 promoters confer susceptibility clinical conditions. Pharmacologic therapy effective once molecular pathogenesis known. hypoactive alleles hyperactive COMT, which degrade synaptic cleft, associated schizophrenia. It insufficient dopaminergic transmission frontal lobe plays development negative symptoms Antipsychotic partial D2 agonist effect may plausible alternative current therapies, would symptom reduction psychotic individuals. possible employing D1/D2 agonists or COMT inhibitors beneficial patients The other disorders, warrants consideration systems careful experiments illumine conferring liability benefit existing new therapies.