尽管自杀行为的遗传学最近取得了进展,遗传因素增加自杀未遂风险的途径尚不清楚.通过考虑精神疾病的作用,我们调查了从家庭/遗传自杀企图风险(FGRSSA)到自杀企图的中介途径。在一个瑞典队列中,我们评估了自杀尝试时间作为FGRSSA和酒精使用障碍的中介效应的函数,吸毒障碍,注意力缺陷/多动障碍,严重的抑郁症,焦虑症,双相情感障碍,和非情感性精神病。按性别在三个年龄段进行了分析:15-25岁(女性=850,278,男性=899,366),26-35岁(女性=800,189,男性=861,774),36-45岁(女性=498,285,男性=535,831)。FGRSSA与自杀未遂之间的关联是通过精神疾病介导的。男性饮酒障碍的调解效果最高(15-25岁,HRtotal=1.60[1.59;1.62],调解=14.4%),女性吸毒障碍(25-36岁,HRtotal=1.46[1.44;1.49],调解=11.2%),和女性的重度抑郁症(25-36岁)(HRtotal=1.46[1.44;1.49],调解=7%)和男性(HRtotal=1.50[1.47;1.52],调解=4.7%)。虽然FGRSSA的直接影响在15-25岁时更高,但通过精神疾病进行的调解在成年后期更为突出。我们的研究告知了精神疾病,遗传责任通过这些疾病影响自杀企图风险,根据年龄和性别有不同的贡献。
Despite recent progress in the genetics of suicidal behavior, the pathway by which genetic liability increases suicide attempt risk is unclear. We investigated the mediational pathways from family/genetic risk for suicide attempt (FGRSSA) to suicide attempt by considering the roles of psychiatric illnesses. In a Swedish cohort, we evaluated time to suicide attempt as a function of FGRSSA and the mediational effects of alcohol use disorder, drug use disorder, attention-deficit/hyperactivity disorder, major depression, anxiety disorder, bipolar disorder, and non-affective psychosis. Analyses were conducted by sex in three age periods: 15-25 years (Nfemales = 850,278 and Nmales = 899,366), 26-35 years (Nfemales = 800,189 and Nmales = 861,774), and 36-45 years (Nfemales = 498,285 and Nmales = 535,831). The association between FGRSSA and suicide attempt was mediated via psychiatric disorders. The highest mediation effects were observed for alcohol use disorder in males (15-25 years, HRtotal = 1.60 [1.59; 1.62], mediation = 14.4%), drug use disorder in females (25-36 years, HRtotal = 1.46 [1.44; 1.49], mediation = 11.2%), and major depression (25-36 years) in females (HRtotal = 1.46 [1.44; 1.49], mediation = 7%) and males (HRtotal = 1.50 [1.47;1.52], mediation = 4.7%). While the direct effect of FGRSSA was higher at ages of 15-25, the mediation via psychiatric disorders was more prominent in later adulthood. Our study informs about the psychiatric illnesses via which genetic liability operates to impact suicide attempt risk, with distinct contributions according to age and sex.