Associations Between Growth Differentiation Factor 15 and Anxiety and Depression in the General Population: The Akershus Cardiac Examination 1950 Study

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.