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

Molecular Psychiatry volume 30, pages 4085–4093 (2025)Cite this article

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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.

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Fig. 1: Prevalence of suicidal ideation and attempt in the study sample.
Fig. 2: Interaction between polygenic risk score for ADHD and depression in the association with suicidal ideation and attempt.
Fig. 3: Joint association of ADHD and depression polygenic scores with suicidal ideation and attempt.

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Data availability

Data from the QLSCD are available to authorized researchers via the Centre D’Access aux Données de Recherche de l’Institut de la Statistique du Québec (https://www.jesuisjeserai.stat.gouv.qc.ca). Data from the QNTS are available to authorized researchers via the Groupe de Recherche Sur l’Indaptation Psychosociale chez l’Enfant (https://grip-info.ca).

Code availability

The R code used to generate the results of this study is available upon request.

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Acknowledgements

Drs. Orri, Turecki, Geoffroy, Ouellet-Morin, and Boivin are supported by the Canada Research Chair program. Dr. Orri is supported by an American Foundation for Suicide Prevention Young Investigator Award. Dr Morneau-Vaillancourt is supported by a Banting postdoctoral fellowship from the Social Sciences and Humanities Research Council (510174). Samuele Cortese, NIHR Research Professor (NIHR303122) is funded by the NIHR for this research project. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care. Samuele Cortese is also supported by NIHR grants NIHR203684, NIHR203035, NIHR130077, NIHR128472, RP-PG-0618-20003 and by grant 101095568-HORIZONHLTH- 2022-DISEASE-07-03 from the European Research Executive Agency. This study was supported by Fonds de Recherche du Québec en Santé (FRQS) via the Québec Network on Suicide, Mood Disorders, and Related Disorders as well as by the Canada Research Chairs of Dr. Boivin and Dr. Gouin. The Québec Longitudinal Study of Child Development was supported by funding from the Ministère de la Santé et des Services sociaux, the Ministère de la Famille, the Ministère de l’Éducation et de l’Enseignement supérieur, the Lucie and André Chagnon Foundation, the Institut de recherche Robert-Sauvé en santé et en sécurité du travail, the Research Centre of the Sainte-Justine University Hospital, the Ministère du Travail, de l’Emploi et de la Solidarité sociale and the Institut de la statistique du Québec. Additional funding was received by the Fonds de Recherche du Québec - Santé (FRQS), the Fonds de Recherche du Québec - Société et Culture (FRQSC), the Social Science and Humanities Research Council of Canada (SSHRC), and the Canadian Institutes of Health Research (CIHR). Funding for the primary school data collections of the Quebec Newborn Twin Study comes from Social Science and Humanities Research Council (SSHRC) grant 410-2001-1475. Funding for the age 20 data collection comes from SSHRC grant 435-2014-1536. The sponsors have no role in study design, data analysis and interpretation, and decision to submit for publication. The authors gratefully acknowledge the ongoing contribution of families, children, and teachers in the QLSCD and QNTS. They also thank Héléne Paradis for QNTS data preparation.

Author information

Authors and Affiliations

  1. McGill Group for Suicide Studies, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, QC, Canada

    Massimiliano Orri, Gustavo Turecki & Marie-Claude Geoffroy

  2. Department of Epidemiology, Biostatistics, and Occupational Health, School of Population and Global Health, McGill University, Montreal, QC, Canada

    Massimiliano Orri & Marie-Claude Geoffroy

  3. Danish Research Institute for Suicide Prevention, Mental Health Centre Copenhagen, Copenhagen, Denmark

    Massimiliano Orri

  4. Social, Genetic & Developmental Psychiatry Centre (SGDP), Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), King’s College London, London, UK

    Genevieve Morneau-Vaillancourt

  5. École de criminologie, Université de Montréal, Montréal, QC, Canada

    Genevieve Morneau-Vaillancourt & Isabelle Ouellet-Morin

  6. Research Centre of the Montreal Mental Health University Institute, Université de Montréal, Montreal, QC, Canada

    Isabelle Ouellet-Morin

  7. Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK

    Samuele Cortese

  8. Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK

    Samuele Cortese

  9. Solent NHS Trust, Southampton, UK

    Samuele Cortese

  10. Hassenfeld Children’s Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA

    Samuele Cortese

  11. DiMePRe-J-Department of Precision and Rigenerative Medicine-Jonic Area, University of Bari “Aldo Moro”, Bari, Italy

    Samuele Cortese

  12. Department of Child and Adolescent Psychiatry, University of Bordeaux, Bordeaux, France

    Cedric Galera

  13. Centre Hospitalier Perrens, Bordeaux, France

    Cedric Galera

  14. INSERM U1219, Bordeaux Population Health Center, Bordeaux, France

    Cedric Galera & Michel Boivin

  15. Ecole de psychologie, Université Laval, Quebec, QC, Canada

    Ivan Voronin & Ginette Dionne

  16. Ecole de psychoeducation, Université de Montréal, Montreal, QC, Canada

    Frank Vitaro

  17. Departement de psychologie, Université du Québec à Montréal, Montreal, QC, Canada

    Mara R. Brendgen

  18. Department of Psychology, The Pennsylvania State University, State College, PA, USA

    Stephane Paquin

  19. Division of Child and Adolescent Psychiatry, Department of Psychiatry, University Hospital of Lausanne CHUV, Lausanne, Switzerland

    Alberto Forte

  20. Departements de pediatrie et de psychologie, Université de Montréal, Montreal, QC, Canada

    Richard E. Tremblay

  21. Departement de médecine sociale et preventive, Université de Montreal, Montreal, QC, Canada

    Sylvana M. Côté

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  1. Massimiliano Orri
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  2. Genevieve Morneau-Vaillancourt
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  3. Isabelle Ouellet-Morin
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  6. Ivan Voronin
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  8. Mara R. Brendgen
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  10. Stephane Paquin
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  16. Michel Boivin
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Contributions

Dr. Orri conceptualised the study, wrote the initial draft, conducted the statistical analyses. Dr. Voronin and Paquin contributed to data analysis (polygenic scores). All authors contributed to data interpretation and drafting of the final manuscript. Dr. Orri had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Massimiliano Orri.

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Competing interests

Prof. Cortese has declared reimbursement for travel and accommodation expenses from the Association for Child and Adolescent Central Health (ACAMH) in relation to lectures delivered for ACAMH, the Canadian AADHD Alliance Resource, the British Association of Psychopharmacology, and from Healthcare Convention for educational activity on ADHD, and has received honoraria from Medice. The other authors have no conflict of interest to disclose.

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Orri, M., Morneau-Vaillancourt, G., Ouellet-Morin, I. et al. Joint contribution of polygenic scores for depression and attention-deficit/hyperactivity disorder to youth suicidal ideation and attempt. Mol Psychiatry 30, 4085–4093 (2025). https://doi.org/10.1038/s41380-025-02989-z

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