This longitudinal study of adolescents in the first year of secondary school, examined the relationship between psychological functioning at the beginning of year 7 (mean age 11.25 years) with attainment at the end of year 7 (mean age 11.78 years). Depressive symptoms, school liking and conduct problems predicted lower attainment across time having controlled for the temporal stability in psychological functioning and attainment. School concerns predicted lower attainment for boys only, and the effects of depressive symptoms on later attainment were significantly stronger for boys compared to girls. School liking – and school concerns for boys – remained significant predictors of attainment when controlling for conduct problems. The transition to secondary school may represent a window of opportunity for developing interventions aimed at improving both pupil psychological functioning and attainment.

Medical Research Council.

Key Points Question Do neuropsychiatric disorder genetic risk variants influence developmental trajectories of depression in youth? Findings In this population-based study including 7543 adolescents, distinct depression trajectory classes were identified. A later-adolescence–onset class (17.3% of the sample) showed a typical depression trajectory and was associated with major depressive disorder risk alleles, and an early-adolescence–onset class (9.0%) showed clinically significant symptoms at age 12 years and was associated with schizophrenia and attention-deficit hyperactivity disorder genetic risk, childhood attention-deficit hyperactivity disorder, and neurodevelopmental traits. Meaning Depression in youth is heterogeneous; findings are consistent with emerging evidence for a neurodevelopmental component to some cases of depression and that this component is more likely when onset is very early.

Persistence of ADHD symptoms across childhood and adolescence in the general population is associated with higher PRS for ADHD. Childhood multimorbidity was also associated with persistence of ADHD symptoms and may help to identify children with ADHD whose symptoms are most likely to continue into adolescence.

Longitudinal studies have provided mixed findings regarding the relationship between emotional problems and subsequent poor school attainment. A meta‐analysis of 26 community‐based studies of children and adolescents was performed. Results revealed a prospective association between emotional problems and poor school attainment. More consistent associations were found for depression than anxiety. Moderator analyses indicated that some of the heterogeneity between studies may be due to age and gender, with reduced heterogeneity particularly notable for school grades during early adolescence and for anxiety by gender. Findings suggest that early identification and provision of support for young people with emotional problems may be helpful for improving academic outcomes such as school attainment.

Differences in how depression presents in adolescents and adults may be consistent with different pathophysiological mechanisms. For adolescents, we found that vegetative/physical disturbances were common (loss of energy, changes in weight, appetite and sleep changes). For adults, anhedonia/loss of interest and concentration difficulties were more common.

Key Points Question Are rare copy number variants associated with depression in a large population sample? Findings In this case-control study of 407 074 individuals in the UK Biobank study, neurodevelopmental disorder copy number variants appear to be associated with the risk of depression in those without neurodevelopmental disorders. Physical health, educational attainment, social deprivation, smoking status, and alcohol consumption are variables that partially explain this association, and no evidence was found of an association between measures of copy number variant burden and depression. Meaning Neurodevelopmental copy number variants appear to be associated with increases in the risk of depression in those without neurodevelopmental disorders.

IMPORTANCE Early-life exposures, such as prenatal maternal lifestyle, illnesses, nutritional deficiencies, toxin levels, and adverse birth events, have long been considered potential risk factors for neurodevelopmental disorders in offspring. However, maternal genetic factors could be confounding the association between early-life exposures and neurodevelopmental outcomes in offspring, which makes inferring a causal relationship problematic. OBJECTIVE To test whether maternal polygenic risk scores (PRSs) for neurodevelopmental disorders were associated with early-life exposures previously linked to the disorders. DESIGN, SETTING, AND PARTICIPANTS In this UK population-based cohort study, 7921 mothers with genotype data from the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent testing for association of maternal PRS for attention-deficit/hyperactivity disorder (ADHD PRS), autism spectrum disorder (ASD PRS), and schizophrenia (SCZ PRS) with 32 early-life exposures. ALSPAC data collection began September 6, 1990, and is ongoing. Data were analyzed for the current study from April 1 to September 1, 2018. EXPOSURES Maternal ADHD PRS, ASD PRS, and SCZ PRS were calculated using discovery effect size estimates from the largest available genome-wide association study and a significance threshold of P < .05. MAIN OUTCOMES AND MEASURES Outcomes measured included questionnaire data on maternal lifestyle and behavior (eg, smoking, alcohol consumption, body mass index, and maternal age), maternal use of nutritional supplements and medications in pregnancy (eg, acetaminophen, iron, zinc, folic acid, and vitamins), maternal illnesses (eg, diabetes, hypertension, rheumatism, psoriasis, and depression), and perinatal factors (eg, birth weight, preterm birth, and cesarean delivery). RESULTS Maternal PRSs were available from 7921 mothers (mean [SD] age, 28.5 [4.8] years). The ADHD PRS was associated with multiple prenatal factors, including infections (odds ratio [OR], 1.11; 95% CI, 1.04-1.18), use of acetaminophen during late pregnancy (OR, 1.11; 95% CI, 1.04-1.18), lower blood levels of mercury (β coefficient, −0.06; 95% CI, −0.11 to −0.02), and higher blood levels of cadmium (β coefficient, 0.07; 95% CI, 0.05-0.09). Little evidence of associations between ASD PRS or SCZ PRS and prenatal factors or of association between any of the PRSs and adverse birth events was found. Sensitivity analyses revealed consistent results. CONCLUSIONS AND RELEVANCE These findings suggest that maternal risk alleles for neurodevelopmental disorders, primarily ADHD, are associated with some pregnancy-related exposures. These findings highlight the need to carefully account for potential genetic confounding and triangulate evidence from different approaches when assessing the effects of prenatal exposures on neurodevelopmental disorders in offspring.