Reduced serum adiponectin and exercise predict depression in chronic heart failure patients and affect depressive-like behaviors in a mouse model.

BACKGROUND

Chronic heart failure (CHF) is frequently comorbid with depression and anxiety. Currently, we aim to investigate the association between serum adiponectin levels and depression among patients with CHF.

METHODS

A total of 119 patients with HF in a tertiary hospital in southern China were enrolled. All patients completed the Patient Health Questionnaire-9 (PHQ-9) upon discharge. Serum levels of adiponectin, ghrelin, leptin A, and BDNF were measured. On the basis of PHQ-9 scores, HF patients were divided into non-Dep, mild-Dep, moderate-Dep, and severe-Dep groups. Differences in the levels of cardiac markers and serum mediators between the non/mild-Dep group and the moderate/severe-Dep group were analyzed using weighted univariate and multivariate logistic regression models. An HF C57BL/6 mouse model of depression was established. AdipoRon, an orally active adiponectin receptor agonist, was administered to the mouse model.

RESULTS

A total of 119 patients with CHF were categorized into non-Dep (n=35), mild-Dep (n=46), moderate-Dep (n=20), and severe-Dep groups (n=18). Compared with those in the non-Dep group, adiponectin levels in the Dep group were significantly lower and correlated with increased depression severity in HF patients. Weighted univariate and multivariate regression analyses indicated that adiponectin (OR = 0.719; 95% CI: 0.531-0.975) and exercise duration (OR = 0.655; 95% CI: 0.489-0.877) were potential predictors of CHF comorbid with depression. Spearman correlation analysis revealed a positive correlation between adiponectin levels and exercise frequency/duration, whereas negative correlations were found between depression scores and exercise frequency/duration. Sensitivity analyses with stepwise exclusion of high-risk subgroups (diabetes, systemic inflammation, and severe HF) revealed a significant association between exercise duration and depression. In a depression model in MI mice, serum adiponectin levels were decreased. Compared with single-treatment approaches, the combination of adiponectin receptor agonists and exercise intervention effectively improved depressive-like behaviors in mice and regulated related biomarker levels, with superior effects.

CONCLUSION

Reduced serum adiponectin levels and exercise activity were associated with increased odds of having CHF comorbid with depression. Activation of the adiponectin/AdipoR1 pathway combined with exercise intervention has potential benefits for the prevention of depression in patients with HF.