Birthweight predicts unfavorable adolescent immunometabolic trajectories leading to adult atypical depression in the ALSPAC cohort.

内容摘要

Lower birthweight, a marker of prenatal adversity, is associated with adverse health outcomes, including psychopathology and immune-metabolic alterations. This study tests whether longitudinal trajectories of chronic immune-metabolic alteration across adolescence, a period of rapid physiological changes, are predicted by birthweight and associated with subsequent depression risk, notably the atypical subtype. We aim to clarify pathways linking prenatal adversity to psychopathology. We derived a latent immune-metabolic factor at ages 15, 17, and 24 from standardized C-reactive protein and Homeostatic measurement of insulin resistance in participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N = 3000). We used latent class mixed modeling to identify immune-metabolic trajectory classes. Depression at 24 was measured on the International Classification of Diseases-10 criteria; atypical features were operationalized as the presence of neurovegetative symptoms (e.g. hypersomnia, hyperphagia). Inverse-probability weighting was used to mitigate selection bias. Here we show that a four-class quadratic model best fits the data. Membership in the late-adolescence-peaking trajectory is associated with higher odds of depression at 24 (Weighted-Beta=0.767, p = 0.047, OR = 2.15, 95%CI:1.20-3.88), and, notably, of depression with atypical symptoms (Weighted-Beta=1.25, p = 0.0035, OR = 3.50, 95%CI:1.50-8.11). Birthweight is inversely associated with odds of experiencing an unfavourable late-peak trajectory group (Weighted-Beta = -1.99, robust p = 0.0313, OR = 0.14, 95%CI:0.02-0.84). Sex demonstrates a marginal moderating effect (p = 0.050), with the association between birthweight and late-peak trajectory membership being more pronounced in females. Findings provide longitudinal evidence that prenatal adversity, indexed by lower birthweight, predicts individuals experiencing unfavourable adolescent immune-metabolic trajectories that are associated with adult depression, particularly with atypical features. Results suggest that developmental immune-metabolic trajectories could eventually inform patient clinical stratification and point to late adolescence as a possible intervention window. In this study, through longitudinal data modeling, we investigated how fluctuations in immune-metabolic biomarkers during adolescence and early adulthood contribute to depression, specifically the atypical subtype characterized by oversleeping, increased appetite, and low energy. We also examined whether prenatal adversity, indexed by lower birthweight, could predict an unfavorable biomarker trajectory. We found that a trajectory marked by a surge in immune-metabolic biomarkers during late adolescence is predicted by lower birthweight, especially in women, and increases the risk of atypical depression. These findings suggest that tracking these biological changes can help identify individuals at higher risk for depression. Ultimately, this highlights late adolescence as a critical window for early intervention and emphasizes the lifelong impact of the prenatal environment on both mental and physical health.