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Background <p>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.</p> Methods <p>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 (<i>N</i> = 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.</p> Results <p>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, <i>p</i> = 0.047, OR = 2.15, 95%CI:1.20-3.88), and, notably, of depression with atypical symptoms (Weighted-Beta=1.25, <i>p</i> = 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 <i>p</i> = 0.0313, OR = 0.14, 95%CI:0.02-0.84). Sex demonstrates a marginal moderating effect (<i>p</i> = 0.050), with the association between birthweight and late-peak trajectory membership being more pronounced in females.</p> Conclusions <p>Findings provide longitudinal evidence that prenatal adversity, indexed by lower&#xa0;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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月16日

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  • Qizhou Xia,
  • Carine Parent,
  • Guillaume Elgbeili,
  • Irina Pokhvisneva,
  • Patricia Pelufo Silveira

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.