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Gene – maltreatment interplay in adult ADHD symptoms: main role of a gene–environment correlation effect in a Brazilian population longitudinal study

Molecular Psychiatry (2024)Cite this article

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Abstract

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment’s impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (β = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (β = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(βASRS = 0.51; 95% CI: 0.26;0.77) and (βSDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (β = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.

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Acknowledgements

We thank the 2004 Pelotas Birth cohort participants and their mothers for their participation in the study. This article is based on data from the study “Pelotas Birth Cohort, 2004” conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas, with the collaboration of the Brazilian Public Health Association (ABRASCO). The World Health Organization, National Support Program for Centers of Excellence (PRONEX), Brazilian National Research Council (CNPq), Brazilian Ministry of Health, and Children’s Pastorate supported previous phases of the study. The 11-year follow-up was supported by the Department of Science and Technology (DECIT) of the Brazilian Ministry of Health, CNPq and the Research Support Foundation of the State of São Paulo (FAPESP, grant no 2014/13864-6). The 15-year follow-up was funded by DECIT, CNPq, the Research Support Foundation of the State of Rio Grande do Sul (FAPERGS grant no 21/2551-0002002-4), FAPESP (grant no 2020/07730-8), and the L’Oréal-Unesco-ABC Program for Women in Science in Brazil-2020. The 18-year follow-up was supported by DECIT, CNPq, FAPERGS, L’Oréal-Unesco-ABC Program for Women in Science in Brazil-2020, and by the All for Health Institute. The present research was funded by CNPq (grant no 409224/2021-9). CNPq supports LTR (grant number 308319/2021-4), ISS (303042/2018-4), LAR (308294/2018-1), MHH (305492/2018-7), CB (314661/2021-2), CSP, JM, (306904/2020-9), AJDB and AM (312746/2021-0). LC is a recipient of a CNPq technical support grant (grant number 370504/2023-2).

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Authors and Affiliations

  1. Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil

    Luciana Tovo-Rodrigues, Laísa Camerini, Thais Martins-Silva, Marina Xavier Carpena, Isabel Oliveira Oliveira, Joseph Murray, Aluísio J. D. Barros, Iná S. Santos & Alicia Matijasevich

  2. ADHD Outpatient Program & Development Psychiatry Program, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Luciana Tovo-Rodrigues, Laísa Camerini, Thais Martins-Silva, Marina Xavier Carpena, Luis Augusto Rohde, Mara Helena Hutz & Julia Pasqualini Genro

  3. Human Development and Violence Research Centre (DOVE), Federal University of Pelotas, Pelotas, Brazil

    Luciana Tovo-Rodrigues, Thais Martins-Silva, Marina Xavier Carpena & Joseph Murray

  4. Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brasil

    Carolina Bonilla & Alicia Matijasevich

  5. Institute of Biology, Federal University of Pelotas, Pelotas, Brazil

    Isabel Oliveira Oliveira

  6. Graduate Program in Developmental Disorders, Mackenzie Presbiterian University, São Paulo, Brazil

    Cristiane Silvestre de Paula

  7. National Institute of Developmental Psychiatry for Children and Adolescents & National Center for Research and Innovation in Child Mental Health, Sao Paulo, Brazil

    Luis Augusto Rohde

  8. Medical School Council, UniEduK, São Paulo, Brazil

    Luis Augusto Rohde

  9. Postgraduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

    Mara Helena Hutz

  10. Postgraduate Program in Bioscience, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil

    Julia Pasqualini Genro

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Contributions

LT-R designed the study, collected the data, performed statistical analysis, interpreted the results, and prepared the manuscript. LC performed statistical analysis, interpreted the results, and prepared the manuscript. TM-S also conducted statistical analysis, interpreted results, and contributed to manuscript preparation. MXC collected data, conducted statistical analysis, interpreted results, and contributed to manuscript preparation. CB participated in data interpretation and manuscript writing. IOO contributed to data collection and critically reviewed the manuscript. CSP, JM, and MHH critically reviewed the manuscript. AJDB, ISS, and LAR participated in study conception and design, data collection, and critical manuscript review. JPG participated in study conception and design, data interpretation, manuscript writing, and critical manuscript review. AM contributed to study conception and design, data collection, supervision, manuscript preparation, and critical manuscript review. All authors approved the final version of the manuscript.

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Correspondence to Luciana Tovo-Rodrigues.

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Competing interests

LAR has received grant or research support from, served as a consultant to, and served on the speakers’ bureau of Abdi-Ibrahim, Abbott, Aché, Adium, Aspen, Bial, Medice, Novartis/Sandoz, Pfizer/Upjohn, and Shire/Takeda in the last three years. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LAR have received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Novartis/Sandoz and Shire/Takeda. LAR has received authorship royalties from Oxford Press and ArtMed. The other authors declare that they have no conflict of interest.

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Supplementary information

41380_2024_2589_MOESM1_ESM.docx

Supplementary Table 1. Adjusted linear regression model presenting the relationship of ADHD genetic susceptibility (ADHD-PGS) with self-reported and mother-reported ADHD symptoms at age 18.

41380_2024_2589_MOESM2_ESM.jpg

Supplementary Figure 1. Interaction graphs of the childhood maltreatment moderator effects for the association between ADHD-PGS and self-reported ADHD score (ASRS) at age 18. 2004 Pelotas Birth Cohort

41380_2024_2589_MOESM3_ESM.jpg

Supplementary Figure 2. Interaction graphs of the childhood maltreatment moderator effects for the association between ADHD-PGS and mother-reported ADHD score (SDQ) at age 18. 2004 Pelotas Birth Cohor

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Tovo-Rodrigues, L., Camerini, L., Martins-Silva, T. et al. Gene – maltreatment interplay in adult ADHD symptoms: main role of a gene–environment correlation effect in a Brazilian population longitudinal study. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02589-3

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