Investigating Gene-Environment Interplay Between Bereavement and Polygenic Risk for Attention-Deficit/Hyperactivity Disorder on Externalizing Behaviors During Adolescence

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 nonbereaved: 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 nonbereaved: 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.

Keywords: ALSPAC; bereavement; childhood and adolescence; externalizing disorders; gene-environment interplay.

Figure 1

Zero-Inflated Negative Binomial Estimates of Bereavement and Polygenic Risk Score (PRS) for Attention-Deficit/Hyperactivity Disorder (ADHD) on Externalizing Symptoms After Loss Note:Zero-inflated negative binomial (ZINB) models were run with inverse probability weights on multiply imputed data. For each outcome, 2 different ZINB model results are presented along the y-axis: one modeling the main effect of bereavement and one modeling the main effect of PRS for ADHD (plus covariates, but without mutual adjustment). Odds ratios (ORs; for the ZINB model component modeling zero vs any symptoms) or incidence rate ratios (IRRs; for the component modeling symptom count) + 95% CIs are presented along the x-axis.