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Ragnhild Dypvik¹, Katrine Kveli Fjukstad, Stian Lydersen

¹From the Faculty of Medicine and Health Sciences (Dypvik) and Department of Mental Health, Faculty of Medicine and Health Sciences (Fjukstad, Lydersen), Norwegian University of Science and Technology, Trondheim; Department of Psychiatry, Levanger Hospital (Fjukstad), Nord-Trøndelag Hospital Trust, Levanger; Department of Medical Research, Bærum Hospital (Berge, Tveit), Vestre Viken Hospital Trust, Gjettum; Institute of Clinical Medicine (Tveit, Einvik) and K.G. Jebsen Center for Cardiac Biomarkers, Institute of Clinical Medicine (Røsjø, Omland, Lyngbakken), Faculty of Medicine, University of Oslo, Oslo; and Division of Research and Innovation (Røsjø), Department of Cardiology, Division of Medicine (Omland, Lyngbakken), and Department of Pulmonary Medicine (Einvik), Akershus University Hospital, Lørenskog, Norway.

Biopsychosocial Science and Medicine

|February 5, 2025

Abstract

Objective:

Several studies suggest a bidirectional association between inflammation, and anxiety and depression. Elevated inflammatory cytokines generate and aggravate neuroinflammation, which may play a part in developing psychological symptoms. Growth differentiation factor 15 (GDF-15) is a novel biomarker possibly reflecting fibrosis and inflammation. The aim of the current study was to investigate the associations between levels of GDF-15 and symptoms of anxiety and depression in the general population.

Methods:

We measured GDF-15 in middle-aged persons participating in the Akershus Cardiac Examination 1950 Study. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS), with HADS ≥8 denoting significant symptoms. We used multivariable regression analysis to assess the associations between GDF-15 and HADS, adjusting for levels of C-reactive protein (CRP), demographics, and comorbidities.

Results:

A total of 3638 participants had valid assessment of HADS and measurements of GDF-15 and CRP. The mean age was 63.9 (SD 0.65) years, and 48.8% were women. In adjusted models, levels of GDF-15 were associated with the continuous HADS-D score (β = 0.27, 95% confidence interval [CI] = 0.12 to 0.43) and HADS-D score ≥8 (odds ratio = 1.41, 95% CI = 1.12 to 1.78), but not with the continuous HADS-A score (β = 0.06, 95% CI = -0.12 to 0.24) or HADS-A score ≥8 (odds ratio = 1.06, 95% CI = 0.88 to 1.27).

Conclusions:

Levels of GDF-15 are independently associated with symptoms of depression in the general population. Our results reinforce the notion that inflammation may be a contributing factor for the development of clinical depression.

Registration:

ClinicalTrials.gov identifier NCT01555411 (Akershus Cardiac Examination [ACE] 1950 Study), https://clinicaltrials.gov/study/NCT01555411.

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