Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Department of Human Anatomy and Psychobiology, University of Murcia, Murcia, Spain.
Mol Psychiatry. 2018 Jul;23(7):1590-1596. doi: 10.1038/mp.2017.130. Epub 2017 Jul 11.
The diathesis-stress theory for depression states that the effects of stress on the depression risk are dependent on the diathesis or vulnerability, implying multiplicative interactive effects on the liability scale. We used polygenic risk scores for major depressive disorder (MDD) calculated from the results of the most recent analysis from the Psychiatric Genomics Consortium as a direct measure of the vulnerability for depression in a sample of 5221 individuals from 3083 families. In the same we also had measures of stressful life events and social support and a depression symptom score, as well as DSM-IV MDD diagnoses for most individuals. In order to estimate the variance in depression explained by the genetic vulnerability, the stressors and their interactions, we fitted linear mixed models controlling for relatedness for the whole sample as well as stratified by sex. We show a significant interaction of the polygenic risk scores with personal life events (0.12% of variance explained, P-value=0.0076) contributing positively to the risk of depression. Additionally, our results suggest possible differences in the aetiology of depression between women and men. In conclusion, our findings point to an extra risk for individuals with combined vulnerability and high number of reported personal life events beyond what would be expected from the additive contributions of these factors to the liability for depression, supporting the multiplicative diathesis-stress model for this disease.
抑郁症的素质-应激理论认为，应激对抑郁风险的影响取决于素质或易感性，这意味着在易感性量表上存在相乘的交互作用。我们使用了最近由精神病学基因组学联盟（Psychiatric Genomics Consortium）进行的分析结果计算出的用于重度抑郁症（MDD）的多基因风险评分（polygenic risk score），作为对 3083 个家庭中的 5221 个人样本的抑郁易感性的直接衡量标准。我们还对生活应激事件和社会支持进行了测量，并对大多数个体进行了 DSM-IV MDD 诊断，同时还对抑郁症状进行了评分。为了估计遗传易感性、应激源及其相互作用对抑郁的解释方差，我们使用线性混合模型对整个样本进行了控制，同时按性别分层进行了控制。我们发现多基因风险评分与个人生活事件之间存在显著的相互作用（解释方差的 0.12%，P 值=0.0076），对抑郁风险有正向贡献。此外，我们的结果表明，女性和男性之间的抑郁病因可能存在差异。总之，我们的研究结果表明，在个人易感性和报告的个人生活事件数量较高的情况下，个体面临着额外的抑郁风险，这超出了这些因素对抑郁易感性的累加贡献，支持了这种疾病的相乘素质-应激模型。
