Orri Massimiliano, Morneau-Vaillancourt Genevieve, Ouellet-Morin Isabelle, Cortese Samuele, Galera Cedric, Voronin Ivan, Vitaro Frank, Brendgen Mara R, Dionne Ginette, Paquin Stephane, Forte Alberto, Turecki Gustavo, Tremblay Richard E, Côté Sylvana M, Geoffroy Marie-Claude, Boivin Michel
McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada.
Mol Psychiatry. 2025 Apr 4. doi: 10.1038/s41380-025-02989-z.
Children presenting comorbid attention-deficit/hyperactivity disorder (ADHD) and depression symptoms have higher risks of later suicidal ideation and attempt. However, it is unclear to what extent this risk stems from individual differences in the genetic predisposition for ADHD and/or depression. We investigated the unique and combined contribution of genetic predisposition to ADHD and depression to suicidal ideation and attempt by early adulthood. Data were from two longitudinal population-based birth cohorts, the Quebec Longitudinal Study of Child Development and the Quebec Newborn Twin Study (total N = 1207). Genetic predisposition for ADHD and depression were measured using polygenic scores. Suicidal ideation and attempt by age 20 years were self-reported via questionnaires. Across the two cohorts, suicidal ideation and attempt were reported by 99 (8.2%) and 75 (6.1%) individuals, respectively. A higher polygenic score for depression was associated with significantly higher risk of suicidal ideation and attempt, while no significant associations were found for ADHD polygenic score. However, we found an interaction between polygenic scores for depression and ADHD in the association with suicide attempt (P = 0.012), but not suicidal ideation (P = 0.897). The association between polygenic score for depression and suicide attempt was significantly stronger for individuals with a higher polygenic score for ADHD. Individuals scoring ≥ 1-SD above the mean for both polygenic scores were at increased risk for suicide attempt compared to individuals with lower scores (OR 4.03, CI 1.64-9.90), as well as compared to individuals scoring ≥ 1-SD above the mean in only depression (OR 2.92, CI 1.01-8.50) or only ADHD (OR 4.88, CI 1.56-15.26) polygenic scores. Our findings suggest that genetic predisposition for ADHD and depression contributes to increase the risk of suicide attempt in a multiplicative, rather that additive, way. Our results contribute to our understanding of the etiology of suicide risk and may inform screening and risk stratification.
同时患有注意力缺陷多动障碍（ADHD）和抑郁症状的儿童，日后出现自杀意念和自杀未遂的风险更高。然而，尚不清楚这种风险在多大程度上源于ADHD和/或抑郁症遗传易感性的个体差异。我们调查了ADHD和抑郁症遗传易感性对成年早期自杀意念和自杀未遂的独特及综合影响。数据来自两个基于人群的纵向出生队列，即魁北克儿童发展纵向研究和魁北克新生儿双胞胎研究（总样本量N = 1207）。使用多基因分数来衡量ADHD和抑郁症的遗传易感性。通过问卷调查自我报告20岁时的自杀意念和自杀未遂情况。在这两个队列中，分别有99名（8.2%）和75名（6.1%）个体报告有自杀意念和自杀未遂情况。抑郁症多基因分数越高，自杀意念和自杀未遂的风险显著越高，而ADHD多基因分数未发现显著关联。然而，我们发现抑郁症和ADHD的多基因分数在与自杀未遂的关联中存在交互作用（P = 0.012），但在与自杀意念的关联中不存在交互作用（P = 0.897）。对于ADHD多基因分数较高的个体，抑郁症多基因分数与自杀未遂之间的关联显著更强。与得分较低的个体相比，两个多基因分数均高于均值1个标准差的个体自杀未遂风险增加（比值比4.03，置信区间1.64 - 9.90），与仅抑郁症多基因分数高于均值1个标准差的个体相比（比值比2.92，置信区间1.01 - 8.50）以及仅ADHD多基因分数高于均值1个标准差的个体相比（比值比4.88，置信区间1.56 - 15.26）也是如此。我们的研究结果表明，ADHD和抑郁症的遗传易感性以相乘而非相加的方式增加自杀未遂的风险。我们的结果有助于我们理解自杀风险的病因，并可能为筛查和风险分层提供参考。
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