Investigating gene-environment interplay between bereavement and polygenic risk for ADHD on externalizing behaviors during adolescence

Ana Lucia Espinosa Dice*, Henri Garrison-Desany, Andrew Ratanatharathorn, Henning Tiemeier, George Davey Smith, Christy A. Denckla

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Objective
The death of a close friend during adolescence may have a negative impact on one’s mental health. However, existing literature has focused primarily on internalizing disorders, leaving the domain of externalizing behaviors understudied. Furthermore, the role of genetics in shaping post-bereavement psychopathology is not understood. In response, we examine potential interplay between polygenic liability for attention-deficit/hyperactivity disorder (ADHD) and bereavement of a close friend in shaping risk of post-loss externalizing symptoms among adolescents.

Method
We examined self-reported loss of a close friend between ages 12 and 16 years and a polygenic risk score (PRS) for ADHD in a sample of 3,922 adolescents from the Avon Longitudinal Study of Parents and Children. Outcomes at age 16.5 included 2 subscales of the Strengths and Difficulties Questionnaire: hyperactivity/inattention symptoms and conduct problems. Zero-inflated negative binomial (ZINB) models addressed the zero-skewed outcome distribution, and likelihood ratio tests for model comparison were used to detect gene–environment interplay.

Results
Nearly 1 in 10 adolescents reported losing a close friend. After adjusting for pre-loss psychopathology, bereavement independently predicted higher hyperactivity/inattention symptom count (bereaved vs non-bereaved: incidence rate ratio [IRR] = 1.18; 95% CI = 1.05-1.31), whereas the PRS for ADHD did not; neither were associated with the odds of zero (vs any) symptoms. Similarly, a model that included bereavement but not PRS best described the observed variation in conduct problems (bereaved vs non-bereaved: IRR = 1.40; 95% CI = 1.13-1.73).

Conclusion
Our findings reinforce the negative impact that losing a friend may have on an adolescent’s mental health, and suggest that externalizing symptoms among bereaved youth warrant clinical attention. Results from ZINB models reveal that bereavement may aggravate the severity or number of existing externalizing symptoms among those who would exhibit externalizing problems regardless. Genetic liability for ADHD may not augment the prediction of risk for psychopathology after bereavement, although better-powered samples are needed.
Original languageEnglish
JournalJournal of the American Academy of Child & Adolescent Psychiatry
Early online date27 May 2024
DOIs
Publication statusE-pub ahead of print - 27 May 2024

Bibliographical note

Support for the analyses in the present report was funded by the National Institute of Mental Health (Grant ref: K23MH117278, T32 MH 017119) to CAD and ALED. GDS works within the MRC Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1 & MC_UU_00032/01). UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). This publication is the work of the authors, and CAD will serve as guarantor for the contents of this paper.

Structured keywords

  • Bristol Population Health Science Institute

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