Sidorchuk Anna, Kuja-Halkola Ralf, Runeson Bo, Lichtenstein Paul, Larsson Henrik, Rück Christian, D'Onofrio Brian M, Mataix-Cols David, Fernández de la Cruz Lorena
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Mol Psychiatry. 2021 Mar;26(3):974-985. doi: 10.1038/s41380-019-0417-1. Epub 2019 Apr 8.
Obsessive-compulsive disorder (OCD) is associated with high risk of suicide. It is yet unknown whether OCD and suicidal behaviors coaggregate in families and, if so, what are the mechanisms underlying this coaggregation. In a population-based birth cohort and family study, we linked individuals born in Sweden in 1967-2003 (n = 3,594,181) to their parents, siblings, and cousins, and collected register-based diagnoses of OCD, suicide attempts, and deaths by suicide and followed them until December 31, 2013. We also applied quantitative genetic modeling to estimate the contribution of genetic and environmental factors to the familial coaggregation of OCD and suicidal behavior. An elevated risk of suicide attempts was observed across all relatives of individuals with OCD, increasing proportionally to the degree of genetic relatedness, with odds ratios (OR) ranging from 1.56 (95% confidence interval (CI) 1.49-1.63) in parents to 1.11 (95% CI 1.07-1.16) in cousins. The risk of death by suicide also increased alongside narrowing genetic distance, but was only significant in parents (OR 1.55; 95% CI 1.40-1.72) and full siblings (OR 1.80; 95% CI 1.43-2.26) of individuals with OCD. Familial coaggregation of OCD and suicide attempts was explained by additive genetic factors (60.7%) and non-shared environment (40.4%), with negligible contribution of shared environment. Similarly, familial coaggregation with death by suicide was attributed to additive genetics (65.8%) and nonshared environment (34.2%). Collectively, these observations indicate that OCD and suicidal behaviors coaggregate in families largely due to genetic factors. The contribution of unique environment is also considerable, providing opportunities to target high-risk groups for prevention and treatment.
强迫症(OCD)与自杀风险高相关。强迫症和自杀行为在家庭中是否共同聚集,以及如果是这样,这种共同聚集背后的机制是什么,目前尚不清楚。在一项基于人群的出生队列和家庭研究中,我们将1967年至2003年在瑞典出生的个体(n = 3,594,181)与其父母、兄弟姐妹和表亲进行了关联,并收集了基于登记的强迫症、自杀未遂以及自杀死亡诊断信息,并对他们进行随访直至2013年12月31日。我们还应用定量遗传模型来估计遗传和环境因素对强迫症和自杀行为家庭共同聚集的贡献。在强迫症患者的所有亲属中均观察到自杀未遂风险升高,且与遗传相关性程度成比例增加,优势比(OR)范围从父母的1.56(95%置信区间(CI)1.49 - 1.63)到表亲的1.11(95% CI 1.07 - (此处原文有误,应为1.16)1.16)。自杀死亡风险也随着遗传距离的缩小而增加,但仅在强迫症患者的父母(OR 1.55;95% CI 1.40 - 1.72)和同胞手足(OR 1.80;95% CI 1.43 - 2.26)中显著。强迫症和自杀未遂的家庭共同聚集由加性遗传因素(60.7%)和非共享环境(40.4%)解释,共享环境的贡献可忽略不计。同样,与自杀死亡的家庭共同聚集归因于加性遗传(65.8%)和非共享环境(34.2%)。总体而言,这些观察结果表明,强迫症和自杀行为在家庭中共同聚集主要是由于遗传因素。独特环境的贡献也相当大,为针对高危群体进行预防和治疗提供了机会。