Immune disturbances cluster around specific depressive phenotypes under conditions of structural adversity

Depression, immune-metabolic alterations and mortality in haemodialysis: a prospective cohort study

Depression may identify a clinically relevant risk state among people receiving haemodialysis and require validation in larger, prospectively sampled cohorts, including potential sex differences in routine biomarkers.

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

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.

Exploratory study of the association between blood immune markers and clinical symptoms in adolescent depression: Stratified by body mass index.

High BMI correlates with more severe depressive symptoms and increased inflammatory status in adolescents with MDD, especially among females, suggesting that interventions targeting immune and metabolic pathways may offer additional therapeutic benefits.

Depressive symptom heterogeneity and mortality in a prospective U.S. cohort.

Genetic clusters of BMI reveal symptom-specific causal effects on depression.

It is indicated that the causal effect of BMI on depression detected in typical non-clustered Mendelian randomization is driven to an extent by appetite, with no or inconsistent evidence for effects on core psychological symptoms such as anhedonia and depressed mood.

Allostatic load profiles, resilience, and psychosocial adaptation in young adults

Introduction Allostatic load (AL) reflects the cumulative physiological burden on the body, quantified using biomarkers across multiple systems. The current study identified latent AL profiles in young adults and examined whether resilience moderates associations between AL and depressive symptoms, social functioning, and role functioning. Methods A total of 165 nonclinical young adults (84 women; aged 19–30 years) provided data on 15 biomarkers spanning the hypothalamic-pituitary-adrenal axis, oxidative stress, inflammatory-immune, lipid/glucose-metabolic, and renal systems, which were z-standardized. Latent profile analysis was conducted using the mclust package in R. Moderated regression models examined depressive symptoms, social functioning, and role functioning as outcomes of AL profile, resilience, and their interaction, adjusting for age, sex, and cognitive ability. Percentile bootstrap confidence intervals were estimated (R = 5,000). Results A two-profile solution was retained based on classification quality and interpretability, yielding control and higher-dysregulation profiles (n = 132 and n = 33, respectively; entropy = 0.965; average posterior probability = 0.993). The higher-dysregulation profile showed relatively elevated dysregulation, particularly in inflammatory-immune and lipid/glucose-metabolic markers. Resilience was inversely associated with depressive symptoms [b = −0.138, p < 0.001, 95% CI (−0.199, −0.079)], and a significant AL profile × resilience interaction [b = −0.335, p < 0.001, 95% CI (−0.645, −0.055)] indicated that this association was stronger in the higher-dysregulation group. A similar interaction was observed for social functioning (b = 0.038, p < 0.001, 95% CI [0.003, 0.063]), whereas the interaction for role functioning was not significant. Discussion These findings suggest that person-centered AL profiles capture heterogeneous physiological risk patterns. Resilience showed stronger associations with lower depressive symptoms and better social functioning among individuals with relatively greater physiological dysregulation, highlighting profile-dependent links between psychological resilience and psychosocial adaptation in young adulthood.