Body mass index modifies symptom-specific metabolomic associations with depressive symptoms in the Estonian Biobank
- 1University of Tartu, Institute of Genomics
Abstract
BackgroundMetabolomic studies of depression have yielded heterogeneous findings, potentially because metabolic correlates differ across symptoms and metabolic states. We examined symptom-specific metabolomic associations and whether body mass index (BMI) modifies these relationships.
MethodsWe analyzed 83,717 Estonian Biobank participants (70.6% female) with 249 Nightingale metabolite measures and 14 lifetime depressive symptoms. Logistic regression models progressively adjusted for sociodemographic, lifestyle, medication, and BMI factors. BMI-related attenuation and metabolite x BMI interactions were evaluated, followed by self-organizing map analyses of broader metabolic context.
ResultsBefore BMI adjustment, 660 metabolite-symptom associations were Bonferroni-significant; 136 were significant after BMI adjustment, including 105 retained associations. Weight-related associations showed the strongest BMI dependence: none of 199 weight-gain associations and 2 of 115 weight-loss associations were retained. Among 691 preselected metabolite-symptom pairs, 211 (30.5%) showed significant metabolite x BMI interactions after false discovery rate correction. Six systemic metabolic profiles were identified, but only 3 of 211 BMI-sensitive pairs showed additional profile-dependent heterogeneity.
ConclusionsCirculating metabolic correlates of depressive symptoms are heterogeneous and strongly dependent on symptom phenotype and BMI-related metabolic context. These findings suggest that metabolic biomarkers in depression should be interpreted in relation to both symptom presentation and metabolic state rather than as uniform correlates of the disorder.
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BibTeX
@misc{kurvits2026body,
title = {{Body mass index modifies symptom-specific metabolomic associations with depressive symptoms in the Estonian Biobank}},
author = {S. Kurvits and N. Taba and Estonian Biobank research team and L. Milani and T. Haller and K. Lehto},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.26361909},
url = {https://www.medrxiv.org/content/10.64898/2026.09.01.26361909v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Body mass index modifies symptom-specific metabolomic associations with depressive symptoms in the Estonian Biobank
AU - S. Kurvits
AU - N. Taba
AU - Estonian Biobank research team
AU - L. Milani
AU - T. Haller
AU - K. Lehto
PY - 2026
DA - 2026/09/01
PB - medRxiv
DO - 10.64898/2026.09.01.26361909
UR - https://www.medrxiv.org/content/10.64898/2026.09.01.26361909v1
AB - BackgroundMetabolomic studies of depression have yielded heterogeneous findings, potentially because metabolic correlates differ across symptoms and metabolic states. We examined symptom-specific metabolomic associations and whether body mass index (BMI) modifies these relationships. MethodsWe analyzed 83,717 Estonian Biobank participants (70.6% female) with 249 Nightingale metabolite measures and 14 lifetime depressive symptoms. Logistic regression models progressively adjusted for sociodemographic, lifestyle, medication, and BMI factors. BMI-related attenuation and metabolite x BMI interactions were evaluated, followed by self-organizing map analyses of broader metabolic context. ResultsBefore BMI adjustment, 660 metabolite-symptom associations were Bonferroni-significant; 136 were significant after BMI adjustment, including 105 retained associations. Weight-related associations showed the strongest BMI dependence: none of 199 weight-gain associations and 2 of 115 weight-loss associations were retained. Among 691 preselected metabolite-symptom pairs, 211 (30.5%) showed significant metabolite x BMI interactions after false discovery rate correction. Six systemic metabolic profiles were identified, but only 3 of 211 BMI-sensitive pairs showed additional profile-dependent heterogeneity. ConclusionsCirculating metabolic correlates of depressive symptoms are heterogeneous and strongly dependent on symptom phenotype and BMI-related metabolic context. These findings suggest that metabolic biomarkers in depression should be interpreted in relation to both symptom presentation and metabolic state rather than as uniform correlates of the disorder.
ER -