Neurogenetics Section, Molecular Brain Science Department, Campbell Family Mental Health Research Institute, and General Adult Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Curr Top Behav Neurosci. 2021;49:385-398. doi: 10.1007/7854_2020_205.
Pharmacogenetics has become increasingly important in the treatment of psychiatric disorders because approximately 50% of individuals who take psychotropic medications do not typically respond to them. Obsessive-compulsive disorder (OCD) is one such chronic and often debilitating mental illness with significant non-response to even the first-line medication, serotonin reuptake inhibitors. Precision medicine utilizing genetic testing panels has received significant attention based on the evidence that the variability of antidepressant response and adverse effects is partly due to the variability in an individual's genome. Thus, extensive research has investigated the role of genetic factors on antidepressant response in major depressive disorder (MDD) and their utility for guiding antidepressant treatment to significantly improving outcomes in individuals with MDD. However, limited progress remains in the pharmacogenetics of OCD. This chapter will provide an overview of the recent findings in the pharmacogenetics of OCD. Promising results with limited replications have been reported for the cytochrome P450 liver metabolism genes in addition to several serotonergic and glutamatergic system genes, which may play an important role in antidepressant response in the treatment of OCD.
药物遗传学在精神疾病的治疗中变得越来越重要,因为大约有 50%的服用精神药物的个体通常对其没有反应。强迫症(OCD)就是这样一种慢性且常常使人衰弱的精神疾病,即使是一线药物——血清素再摄取抑制剂,也有相当大的比例没有反应。基于抗抑郁药反应和不良反应的变异性部分归因于个体基因组的变异性这一证据,利用基因检测面板的精准医学受到了极大的关注。因此,大量研究调查了遗传因素在重度抑郁症(MDD)中的抗抑郁反应中的作用及其用于指导抗抑郁治疗的效用,以显著改善 MDD 患者的预后。然而,在强迫症的药物遗传学方面进展有限。本章将概述强迫症药物遗传学的最新发现。除了几个血清素能和谷氨酸能系统基因外,还报道了细胞色素 P450 肝代谢基因在强迫症治疗中的抗抑郁反应方面具有有希望的结果,但这些结果的可重复性有限。