Metabolites and depressive symptoms: Network- and longitudinal analyses from the Finnish Depression and Metabolic Syndrome in Adults (FDMSA) Study

Guro Pauck Bernhardsen; Owen Thomas; Pekka Mäntyselkä; Leo Niskanen; Mauno Vanhala; Hannu Koponen; Soili M Lehto

doi:10.1016/j.jad.2023.11.070

Metabolites and depressive symptoms: Network- and longitudinal analyses from the Finnish Depression and Metabolic Syndrome in Adults (FDMSA) Study

J Affect Disord. 2024 Feb 15:347:199-209. doi: 10.1016/j.jad.2023.11.070. Epub 2023 Nov 22.

Authors

Guro Pauck Bernhardsen¹, Owen Thomas², Pekka Mäntyselkä³, Leo Niskanen⁴, Mauno Vanhala⁵, Hannu Koponen⁶, Soili M Lehto⁷

Affiliations

¹ Department of Research and Development, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway. Electronic address: guro.pauck.bernhardsen@ahus.no.
² Division of Research and Innovation, Akershus University Hospital, Lørenskog, Norway.
³ Institute of Public Health and Clinical Nutrition, General Practice, University of Eastern Finland, Kuopio, Finland; Clinical Research and Trials Centre, Kuopio University Hospital, Wellbeing Services County of North Savo, Kuopio, Finland.
⁴ Institute of Public Health and Clinical Nutrition, General Practice, University of Eastern Finland, Kuopio, Finland; Departments of Internal Medicine, Endocrinology/Diabetology, Päijät-Häme Central Hospital, Lahti, Finland; Eira Medical Center and Hospital, Helsinki, Finland.
⁵ Institute of Public Health and Clinical Nutrition, General Practice, University of Eastern Finland, Kuopio, Finland.
⁶ Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁷ Department of Research and Development, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry, University of Helsinki, Helsinki, Finland.

PMID: 38000471
DOI: 10.1016/j.jad.2023.11.070

Abstract

Background: Depression is associated with metabolic abnormalities linked to metabolic syndrome and tissue inflammation, but the interplay between metabolic markers and their association with subsequent depression is unknown. Therefore, we aimed to describe the network of metabolites and their prospective association with depressive symptoms.

Methods: The Finnish Depression and Metabolic Syndrome in Adults (FDMSA) cohort, originally a prospective case-control study, comprised a group with Beck Depression Inventory (BDI)-I scores ≥10 at baseline, and controls (n = 319, BDI-I < 10); mean (sd) follow-up time: 7.4 (0.7) years. Serum metabolic biomarkers were determined by proton nuclear magnetic resonance (NMR), and depressive symptoms sum-score by using the BDI-I. We examined the prospective associations between metabolites at baseline and BDI score at follow-up utilizing multivariate linear regression, parsimonious predictions models and network analysis.

Results: Some metabolites tended to be either negatively (e.g. histidine) or positively associated (e.g. glycoprotein acetylation, creatinine and triglycerides in very large high density lipoproteins [XL-HDL-TG]) with depressive symptoms. None of the associations were significant after correction for multiple testing. The network analysis suggested high correlation among the metabolites, but that none of the metabolites directly influenced subsequent depressive symptoms.

Limitations: Although the sample size may be considered satisfactory in a prospective context, we cannot exclude the possibility that our study was underpowered.

Conclusions: Our results suggest that the investigated metabolic biomarkers are not a driving force in the development of depressive symptoms. These findings should be confirmed in studies with larger samples and studies that account for the heterogeneity of depressive disorders.

Keywords: Depressive symptoms; Longitudinal study; Metabolic markers; Metabolomics; Network analysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers
Case-Control Studies
Depression / diagnosis
Finland / epidemiology
Humans
Metabolic Syndrome* / complications

Substances

Biomarkers