Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort
Year: 2025
Type: article
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=1709-3410); 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=2256). 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 depression =13.11, 95% CI 9.59-17.90; RR GAD =11.77, 95% CI 8.58-16.14) and adulthood-onset (RR depression =6.25, 95% CI 4.50-8.68; RR GAD =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.
Source: Molecular Psychiatry
Authors: Ruby S. M. Tsang, Daniel Stow, Alex S. F. Kwong, Nicholas A. Donnelly, Holly Fraser, Inês Barroso, Peter A. Holmans, Michael J. Owen, Megan L. Wood, George Kirov, James T. R. Walters, Peter A. Holmans, Jane Lynch, Ioanna K. Katzourou, Jack F. G. Underwood, David A. van Heel, Sarah Finer, John A. A. Macleod, Julie P. Clayton, Jane Sprackman, Shahid Khan, Rupert A. Payne, Mark Mon-Williams, Nabila Ali, Hilary C. Martin, Thomas Werge, Andrés Ingason, Morteza Vaez, Lam O. Huang, Marianne B. M. van den Bree, Nicholas J. Timpson, Golam M. Khandaker
Institutions: University of Bristol, MRC Integrative Epidemiology Unit, Queen Mary University of London, University of Edinburgh, Avon and Wiltshire Mental Health Partnership NHS Trust, University of Exeter, Cardiff University, University of Leeds, Blizard Institute, Wellcome Sanger Institute, Mental Health Services, Copenhagen University Hospital, NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust
Language: English
Subfield: Biological Psychiatry
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: 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
Awards: G1131969086, G1465635051, G1653957966, G1684393010, G1793884970, Improving mental health outcomes in children born with an orofacial cleft: Identifying children at most risk to target clinical provision, Psychosis Immune Mechanism Stratified Medicine Study (PIMS), G2538597952, G303234583, G3176767667, G3215161164, G323433674, G324601231, G3288322216, Population Research UK Coordination Hub, G3507283293, G3609641447, CHECKPOINT: Finding immune & metabolic pathways to SMI, G363450064, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3987754321, G4059666690, The South Wales and South West England Mental Health Platform Hub, Inflammation and Immunity in Depression: from novel mechanisms towards therapeutics, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., G5189661712, Immunopsychiatry: Investigating the role of inflammation in depression and other psychiatric disorders, 7/9 Rare Genetic Disorders as a Window into the Genetic Architecture of Mental Disorders, G6223152210, G6342754709, G6487373758, Identifying the nature, causes and consequences of youth depression trajectories, Mendelian randomization to hypothesis-free causal inference, Physical and mental health multimorbidity across the lifespan (LIfespaN multimorbidity research Collaborative (LINC))., The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., The impact of schizophrenia-associated copy number variants on cortical network dynamics, G8201869620, What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolomic phenotyping., The Sleep Detectives: Sleep stratification in young people at high risk of psychosis, G8398670486, G8502142660, G8666504171, G880665389, IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence, G942680792
OpenAlex ID: W4415671886