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IMPORTANCE Longitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear. OBJECTIVE To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis. DESIGN, SETTING, AND PARTICIPANTS The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments. MEASUREMENT OF EXPOSURE Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years. MAIN OUTCOMES AND MEASURES Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule–Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview. RESULTS After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner. CONCLUSIONS AND RELEVANCE Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.

Background: The coronavirus disease 2019 (COVID-19) pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences. Aims: To quantify the prevalence of depression, anxiety and mental wellbeing before and during the COVID-19 pandemic. To identify groups at risk of depression and/or anxiety during the pandemic. Methods: Data were from two generations of the Avon Longitudinal Study of Parents and Children (ALSPAC): the index generation (ALSPAC-young, n=2850, mean age=28), parent's generation (ALSPAC-parents, n=3720, mean age=59), and Generation Scotland (GS, n=4233, mean age=59). Depression was measured using the Short Mood and Feelings Questionnaire (SMFQ) in ALSPAC and the Patient Health Questionnaire (PHQ-9) in GS. Anxiety and mental wellbeing were measured using the Generalised Anxiety Disorder Assessment (GAD-7) and the Short Warwick Edinburgh Mental Wellbeing Scale. Results: Depression during COVID-19 was similar to pre-pandemic levels in ALSPAC-young, but those experiencing anxiety almost doubled during COVID-19: 24% (95% CI: 23%, 26%) compared to pre-pandemic levels of 13% (95% CI: 12%, 14%). In both ALSPAC and Generation Scotland, anxiety and depression during COVID-19 was greater in younger members, in women, in those with preexisting mental/physical health conditions, and in individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression. Conclusions: These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during COVID-19. This is important for planning mental health provisions now and for long-term impact beyond this pandemic.

Key PointsQuestionWhat is the association of differing levels of persistence and severity of postnatal depression with long-term child outcomes?FindingsThis observational study of 9848 women with varying levels of postnatal depression and 8287 children found that, compared with children of women with postnatal depression that did not persist, of either moderate or severe intensity, children of women with persistent and severe depression are at an increased risk for behavioral problems by age 3.5 years as well as lower mathematics grades and depression during adolescence. Furthermore, women with persistent postnatal depression are likely to experience significant depressive symptoms until at least 11 years after childbirth.MeaningWomen with persistent and severe postnatal depression should be prioritized for treatment because they are likely to continue to experience high levels of depressive symptoms and because of the high risk of adverse child development.

IMPORTANCE Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention.OBJECTIVE To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression. DESIGN, SETTING, AND PARTICIPANTSProspective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring.MAIN OUTCOMES AND MEASURES Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision.RESULTS Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression. CONCLUSIONS AND RELEVANCEThe findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.

Our results suggest that depressive symptoms are already associated with differential attentional processing of infant emotion at the very beginning of childbearing. The findings have potential implications for our understanding of the impact of depressive symptoms during pregnancy on the developing mother-infant relationship.

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Key PointsQuestionAre children with autism and autistic traits at greater risk of depression at age 18 years, and are genetic confounding and bullying important in these associations?FindingsAmong 6091 participants in this longitudinal study, children with autism and autistic traits had higher depressive symptom scores than the general population at age 10 years, remaining elevated in an upward trajectory until age 18 years. Social communication impairment was associated with depression at 18 years and was substantially mediated by bullying.MeaningSocial communication impairments are an important autistic trait in relation to depression; bullying may be an environmental intermediary and a target for interventions.