Polygenic risks for joint developmental trajectories of internalizing and externalizing problems: findings from the ALSPAC cohort

Abstract

Background Joint developmental trajectories of internalizing and externalizing problems show considerable heterogeneity; however, this can be parsed into a small number of meaningful subgroups. Doing so offered insights into risk factors that lead to different patterns of internalizing/externalizing trajectories. However, despite both domains of problems showing strong heritability, no study has yet considered genetic risks as predictors of joint internalizing/externalizing problem trajectories. Methods Using parallel process latent class growth analysis, we estimated joint developmental trajectories of internalizing and externalizing difficulties assessed across ages 4 to 16 using the Strengths and Difficulties Questionnaire. Multinomial logistic regression was used to evaluate a range of demographic, perinatal, maternal mental health, and child and maternal polygenic predictors of group membership. Participants included 11,049 children taking part in the Avon Longitudinal Study of Parents and Children. Polygenic data were available for 7,127 children and 6,836 mothers. Results A 5‐class model was judged optimal: Unaffected, Moderate Externalizing Symptoms, High Externalizing Symptoms, Moderate Internalizing and Externalizing Symptoms and High Internalizing and Externalizing Symptoms. Male sex, lower maternal age, maternal mental health problems, maternal smoking during pregnancy, higher child polygenic risk scores for ADHD and lower polygenic scores for IQ distinguished affected classes from the unaffected class. Conclusions While affected classes could be relatively well separated from the unaffected class, phenotypic and polygenic predictors were limited in their ability to distinguish between different affected classes. Results thus add to existing evidence that internalizing and externalizing problems have mostly shared risk factors.

Within-person Relations between Domains of Socio-emotional Development during Childhood and Adolescence

“…These findings are in line with previous research highlighting that most mental health problems share common aetiological factors that mostly reflect between-person differences (Caspi & Moffitt, 2018). For instance, polygenic risk scores for ADHD have been found to be associated with both internalising and externalising difficulties, as have a variety of other risk factors such as maternal history of depression or smoking during pregnancy (Murray et al, 2020b;Speyer et al, 2021). With regards to interventions, this suggests that in addition to focusing on targeting pathways that potentially increase the likelihood of someone suffering from one mental health problem to develop another mental health problem, it is highly important to identify those individuals most at risk for developing co-occurring mental health problems based on the broader set of risk factors an individual presents with.…”

Sex/gender differences in individual and joint trajectories of common mental health symptoms in early to middle adolescence

“…Using the "unaffected" class as the reference class, they found that male sex/gender increased the likelihood of membership in several classes characterized by elevations of symptoms in all three domains but not in a class characterized only by elevations in internalizing problems. Speyer et al (2021) found that male sex increased the likelihood of membership in age 4-16 trajectory classes characterized by high internalizing and externalizing symptoms; moderate externalizing symptoms; and high externalizing symptoms compared to the unaffected class. However, male sex did not increase the likelihood of membership in their class characterized by moderate internalizing and externalizing levels.…”

“…Given that secondary symptoms may interact with and/or modify primary symptoms (Drabick & Kendall, 2010), examination of sex/gender differences in joint trajectories of symptoms is important. There have, however, only been a handful of studies examining sex/gender differences in co‐occurring mental health issue trajectories covering the adolescent period (Chen & Simons‐Morton, 2009; Diamantopoulou et al., 2011; Patalay et al., 2017; Speyer et al., 2021). One study examined joint developmental trajectories of ADHD, internalizing, and externalizing symptoms across ages 7–15 (Murray et al., 2020).…”

“…Speyer et al. (2021) found that male sex increased the likelihood of membership in age 4–16 trajectory classes characterized by high internalizing and externalizing symptoms; moderate externalizing symptoms; and high externalizing symptoms compared to the unaffected class. However, male sex did not increase the likelihood of membership in their class characterized by moderate internalizing and externalizing levels.…”

Co-Developmental Trajectories of Parental Psychological Distress and Child Internalizing and Externalizing Problems in Childhood and Adolescence: Associations with Self-Harm and Suicide Attempts

“…Using methods such as latent class growth models (or parallel-process LCGA), ample evidence has also indicated the substantial between-family heterogeneity in the (co-) development of youth internalizing and externalizing problems. Identified trajectory groups have included, for example, pure and co-occurring internalizing and/or externalizing problems at high or moderate levels (or with some changes when transitioning to adolescence) and low symptoms (Murray et al, 2020;Patalay et al, 2017;Speyer et al, 2021). Given that previous studies differ considerably in design, analytical strategy, and age span, these findings have themselves been highly heterogeneous in terms of the specific trajectory groups that have emerged.…”