The association between levels of brain-derived neurotrophic factor and comorbid depression in patients with cardiovascular disease: The Framingham Heart Study

Aim: The current study aims to investigate the association of serum brain-derived neurotrophic factor (BDNF) levels with symptoms of depression in adults with and without prevalent cardiovascular disease (CVD), an often burdensome comorbidity. Methods: This cross-sectional study included participants from FHS (Framingham Heart Study) who had available serum BDNF levels. Depressive symptoms were assessed using the Center for Epidemiological Studies–Depression Scale (CES-D) with a score ≥16 indicating mild to moderate and ≥21 severe depression. Participants taking antidepressant medications were excluded from the study. Results: Altogether 3716 FHS participants were included in the final analysis (mean age, 64.3 ± 11.5 years; 55% women). After adjusting for potential confounders, greater BDNF levels were associated with reduced severe depression risk (odds ratio [OR], 0.78 [95% CI, 0.64–0.96]; P = 0.016). Among participants with CVD, greater BDNF levels were related to lower risk of depressive symptoms (CES-D ≥ 16 OR, 0.63 [95% CI, 0.45–0.89], P = 0.008; CES-D ≥ 21 OR, 0.49 [95% CI, 0.31–0.76], P = 0.002). The inverse relationship between BDNF and depressive symptom risk was present in women with CVD (CES-D ≥ 16 OR, 0.63 [95% CI, 0.40–0.99], P = 0.047; CES-D ≥ 21 OR, 0.38 [95% CI, 0.21–0.70], P = 0.002) but not in men. Conclusion: Lower serum BDNF levels are associated with a higher risk of depressive symptoms in CVD, particularly among women. These findings implicate BDNF in the complex biological mechanisms that underlie prior associations observed between CVD and depression. To reduce the burden of depression in the large proportion of midlife and older adults with CVD, a better understanding of how BDNF may modify these pathways is merited.