Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort

Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiological mechanisms and heterogeneity behind depression, and origins of possible common cardiometabolic comorbidities for depression. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n = 7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n = 1565-2828); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n = 2059 and n = 2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n = 2246). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (RR<sub>depression</sub>=13.11, 95% CI 9.59-17.90; RR<sub>GAD</sub> = 11.77, 95% CI 8.58-16.14) and adulthood-onset (RR<sub>depression</sub>=6.25, 95% CI 4.50-8.68; RR<sub>GAD</sub> = 4.66, 95% CI 3.29-6.60) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and prevention opportunities for adverse cardiometabolic profile in different groups of young people with depression.

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Journal
Molecular Psychiatry
Published
2025-10-29
DOI
https://doi.org/10.1038/s41380-025-03311-7
Primary Topic
Health, Environment, Cognitive Aging
Type
article
Field-Weighted Citation Impact
0.00

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article

Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort

John Macleod, Shahid Ali Khan, James Walters, Rupert Payne et al.
Molecular Psychiatry
Health, Environment, Cognitive Aging
article

Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort

John Macleod, Shahid Ali Khan, James Walters, Rupert Payne, Golam Mohammed Khandaker, David A. van Heel, Holly Fraser, Michael J. Owen, Peter Holmans, Jane Sprackman, Ioanna Katzourou, Ruby S. M. Tsang, Julie Clayton, George Kirov, Mark A Mon-Williams, Inês Barroso, Megan L. Wood, Jack F. G. Underwood, Alex S. F. Kwong, Nicholas J. Timpson, Lam Opal Huang, Sarah Finer, Daniel Stow, Jane Lynch, Hilary C. Martin, Morteza Vaez, Marianne B. M. van den Bree, Nabila Ali, Nicholas A Donnelly, Andrés Ingason, Thomas Werge
article en

Abstract

Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiological mechanisms and heterogeneity behind depression, and origins of possible common cardiometabolic comorbidities for depression. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n = 7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n = 1565-2828); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n = 2059 and n = 2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n = 2246). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (RR<sub>depression</sub>=13.11, 95% CI 9.59-17.90; RR<sub>GAD</sub> = 11.77, 95% CI 8.58-16.14) and adulthood-onset (RR<sub>depression</sub>=6.25, 95% CI 4.50-8.68; RR<sub>GAD</sub> = 4.66, 95% CI 3.29-6.60) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and prevention opportunities for adverse cardiometabolic profile in different groups of young people with depression.

Molecular PsychiatryVol. 31(3)
University of Leeds (GB), Avon and Wiltshire Mental Health Partnership NHS Trust (GB), Queen Mary University of London (GB), University of Exeter (GB), University Hospitals Bristol NHS Foundation Trust (GB), Mental Health Services (DK), At Bristol (GB), Wellcome Sanger Institute (GB), Copenhagen University Hospital (DK), University of Bristol (GB), MRC Epidemiology Unit (GB), Cardiff University (GB), University of Edinburgh (GB)
Wellcome Trust, UK Research and Innovation, NIHR Bristol Biomedical Research Centre, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, University of Bristol, Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, National Institute of Mental Health
Openalex Percentile: Top 59%
Health, Environment, Cognitive Aging
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