Sarginson Jane E, Deakin J F William, Anderson Ian M, Downey Darragh, Thomas Emma, Elliott Rebecca, Juhasz Gabriella
Neuroscience and Psychiatry Unit, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
1] Neuroscience and Psychiatry Unit, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK [2] Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary [3] MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
Neuropsychopharmacology. 2014 Nov;39(12):2857-66. doi: 10.1038/npp.2014.137. Epub 2014 Jun 11.
There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.
越来越多的证据表明，在应对严重或慢性逆境时，遗传因素在抑郁症的易感性差异中起作用。动物研究表明，一氧化氮（NO）信号传导在对应激的抑郁样行为反应中起关键作用。本研究调查了大脑表达的一氧化氮合酶基因NOS1的遗传变异是否会改变心理社会应激与当前抑郁评分之间的关系。我们招募了1222名个体的人群样本，他们提供了DNA以及关于症状和应激的问卷数据。将去年的《危及生命经历清单》（LTE）问卷得分和自我评定的当前经济困难程度用作近期/持续心理社会应激的指标。对20个单核苷酸多态性（SNP）进行了基因分型。当将当前经济困难用作交互项时，确定了包括两个区域单倍型的8个NOS1 SNP与当前抑郁评分之间存在显著关联，这些关联在多重检验校正后仍然显著。位于NOS1调控区域内一个较小的三-SNP单倍型（rs10507279、rs1004356和rs3782218）显示出最强的效应之一，A-C-T单倍型在低逆境水平下与较高的抑郁评分相关，但在高逆境水平下与较低的抑郁评分相关（p = 2.3E - 05）。这些结果表明，NOS1 SNP与经济和心理社会应激源的暴露相互作用，以改变个体对抑郁症的易感性。
