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

Tsang, Ruby S. M., Stow, Daniel, Kwong, Alex S. F., Donnelly, Nicholas A., Fraser, Holly, Barroso, Inês, Holmans, Peter A., Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, Wood, Megan L., Kirov, George, Walters, James T. R., Holmans, Peter A., Lynch, Jane ORCID: https://orcid.org/0000-0003-2863-8594, Katzourou, Ioanna K., Underwood, Jack F. G., van Heel, David A., Finer, Sarah, Macleod, John A. A., Clayton, Julie P., Sprackman, Jane, Khan, Shahid, Payne, Rupert A., Mon-Williams, Mark, Ali, Nabila, Martin, Hilary C., Werge, Thomas, Ingason, Andrés, Vaez, Morteza, Huang, Lam O., van den Bree, Marianne B. M., Timpson, Nicholas J. and Khandaker, Golam M. 2025. Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort. Molecular Psychiatry 10.1038/s41380-025-03311-7

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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 (RRdepression=13.11, 95% CI 9.59-17.90; RRGAD = 11.77, 95% CI 8.58-16.14) and adulthood-onset (RRdepression=6.25, 95% CI 4.50-8.68; RRGAD = 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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Business (Including Economics) Schools > Medicine
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	1359-4184
Date of First Compliant Deposit:	3 November 2025
Date of Acceptance:	15 October 2025
Last Modified:	04 Nov 2025 07:00
URI:	https://orca.cardiff.ac.uk/id/eprint/182085

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