Genetic Architectures of Adolescent Depression Trajectories in 2 Longitudinal Population Cohorts.

Importance: Adolescent depression is characterized by diverse symptom trajectories over time and has a strong genetic influence. Research has determined genetic overlap between depression and other psychiatric conditions; investigating the shared genetic architecture of heterogeneous depression trajectories is crucial for understanding disease etiology, prediction, and early intervention. Objective: To investigate univariate and multivariate genetic risk for adolescent depression trajectories and assess generalizability across ancestries. Design, Setting, and Participants: This cohort study entailed longitudinal growth modeling followed by polygenic risk score (PRS) association testing for individual and multitrait genetic models. Two longitudinal cohorts from the US and UK were used: the Adolescent Brain and Cognitive Development (ABCD; N = 11 876) study and the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 8787) study. Included were adolescents with genetic information and depression measures at up to 8 and 4 occasions, respectively. Study data were analyzed January to July 2023. Main Outcomes and Measures: Trajectories were derived from growth mixture modeling of longitudinal depression symptoms. PRSs were computed for depression, anxiety, neuroticism, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism in European ancestry. Genomic structural equation modeling was used to build multitrait genetic models of psychopathology followed by multitrait PRS. Depression PRSs were computed in African, East Asian, and Hispanic ancestries in the ABCD cohort only. Association testing was performed between all PRSs and trajectories for both cohorts. Results: A total sample size of 14 112 adolescents (at baseline: mean [SD] age, 10.5 [0.5] years; 7269 male sex [52%]) from both cohorts were included in this analysis. Distinct depression trajectories (stable low, adolescent persistent, increasing, and decreasing) were replicated in the ALSPAC cohort (6096 participants; 3091 female [51%]) and ABCD cohort (8016 participants; 4274 male [53%]) between ages 10 and 17 years. Most univariate PRSs showed significant uniform associations with persistent trajectories, but fewer were significantly associated with intermediate (increasing and decreasing) trajectories. Multitrait PRSs-derived from a hierarchical factor model-showed the strongest associations for persistent trajectories (ABCD cohort: OR, 1.46; 95% CI, 1.26-1.68; ALSPAC cohort: OR, 1.34; 95% CI, 1.20-1.49), surpassing the effect size of univariate PRS in both cohorts. Multitrait PRSs were associated with intermediate trajectories but to a lesser extent (ABCD cohort: hierarchical increasing, OR, 1.27; 95% CI, 1.13-1.43; decreasing, OR, 1.23; 95% CI, 1.09-1.40; ALSPAC cohort: hierarchical increasing, OR, 1.16; 95% CI, 1.04-1.28; decreasing, OR, 1.32; 95% CI, 1.18-1.47). Transancestral genetic risk for depression showed no evidence for association with trajectories. Conclusions and Relevance: Results of this cohort study revealed a high multitrait genetic loading of persistent symptom trajectories, consistent across traits and cohorts. Variability in univariate genetic association with intermediate trajectories may stem from environmental factors. Multitrait genetics may strengthen depression prediction models, but more diverse data are needed for generalizability.

Quality of life in parents of autistic children: A transcultural perspective.

Introduction: The concepts of health, illness, and disability as well as the perceptions of autism and quality of life (QoL) vary greatly across cultures and across time. This study sought to explore the interplay of culture on QoL and impact on parents caring for autistic children. Methods: We used a transcultural dataset from seven countries (Australia, Hungary, Malaysia, Romania, Singapore, Spain, and the United Kingdom) with participating parents/carers reporting on the Quality of Life in Autism (QoLA) questionnaire. The QoLA questionnaire is a validated measure of QoL for parents of autistic children, with Part A subscale measuring parental QoL and part B subscale assessing the parental impact of the child's autism spectrum disorder (ASD) symptoms or features. We used the Quade's ranked analysis of covariance to determine significant differences between the countries in relation to QoLA Part A and Part B scores while adjusting for baseline differences using covariates such as parents' gender, child's age, and gender. Additionally, a post-hoc analysis with Bonferroni correction was also conducted to examine multiple pairwise comparisons. Results and conclusion: We found that while the effect of features of ASD (Part B subscale) stayed strongly comparable between cultures, the self-reported parental QoL was most likely determined by different aspects of culture in different countries. It is concluded that while the ASD symptoms or features appear to affect parents in the same way across different countries, the parental QoL may be a culturally informed construct.