Joint contribution of polygenic scores for depression and attention-deficit/hyperactivity disorder to youth suicidal ideation and attempt

Massimiliano Orri; Genevieve Morneau-Vaillancourt; Isabelle Ouellet-Morin; Samuele Cortese; Cedric Galera; Ivan Voronin; Frank Vitaro; Mara R Brendgen; Ginette Dionne; Stephane Paquin; Alberto Forte; Gustavo Turecki; Richard E Tremblay; Sylvana M Côté; Marie-Claude Geoffroy; Michel Boivin

doi:10.1038/s41380-025-02989-z

Joint contribution of polygenic scores for depression and attention-deficit/hyperactivity disorder to youth suicidal ideation and attempt

Mol Psychiatry. 2025 Apr 4. doi: 10.1038/s41380-025-02989-z. Online ahead of print.

Authors

Massimiliano Orri^{1

2

3}, Genevieve Morneau-Vaillancourt^{4

5}, Isabelle Ouellet-Morin^{5

6}, Samuele Cortese^{7

8

9

10

11}, Cedric Galera^{12

13

14}, Ivan Voronin¹⁵, Frank Vitaro¹⁶, Mara R Brendgen¹⁷, Ginette Dionne¹⁵, Stephane Paquin¹⁸, Alberto Forte¹⁹, Gustavo Turecki²⁰, Richard E Tremblay²¹, Sylvana M Côté²², Marie-Claude Geoffroy^{20

23}, Michel Boivin¹⁴

Affiliations

¹ McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada. massimiliano.orri@mcgill.ca.
² Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada. massimiliano.orri@mcgill.ca.
³ Danish Research Institute for Suicide Prevention, Mental Health Centre Copenhagen, Copenhagen, Denmark. massimiliano.orri@mcgill.ca.
⁴ Social, Genetic & Developmental Psychiatry Centre (SGDP), Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King's College London, London, UK.
⁵ École de criminologie, Université de Montréal, Montréal, QC, Canada.
⁶ Research Centre of the Montreal Mental Health University Institute, Université de Montréal, Montreal, QC, Canada.
⁷ Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
⁸ Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.
⁹ Solent NHS Trust, Southampton, UK.
¹⁰ Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA.
¹¹ DiMePRe-J-Department of Precision and Rigenerative Medicine-Jonic Area, University of Bari "Aldo Moro", Bari, Italy.
¹² Department of Child and Adolescent Psychiatry, University of Bordeaux, Bordeaux, France.
¹³ Centre Hospitalier Perrens, Bordeaux, France.
¹⁴ INSERM U1219, Bordeaux Population Health Center, Bordeaux, France.
¹⁵ Ecole de psychologie, Université Laval, Quebec, QC, Canada.
¹⁶ Ecole de psychoeducation, Université de Montréal, Montreal, QC, Canada.
¹⁷ Departement de psychologie, Université du Québec à Montréal, Montreal, QC, Canada.
¹⁸ Department of Psychology, The Pennsylvania State University, State College, PA, USA.
¹⁹ Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital of Lausanne CHUV, Lausanne, Switzerland.
²⁰ McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada.
²¹ Departements de pediatrie et de psychologie, Université de Montréal, Montreal, QC, Canada.
²² Departement de médecine sociale et preventive, Université de Montreal, Montreal, QC, Canada.
²³ Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada.

PMID: 40185901
DOI: 10.1038/s41380-025-02989-z

Abstract

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.

Grants and funding

NIHR203684, NIHR203035, NIHR130077,NIHR128472, RP-PG-0618-20003/DH | National Institute for Health Research (NIHR)