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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.