The association between depression and leptin is mediated by adiposity.

Objective: Animal models suggest that impaired leptin production, or leptin resistance despite increased leptin levels, may contribute to depression. The link between leptin and depression could be mediated by obesity, which is more common in depression and increases leptin production.

Methods: We administered the Beck Depression Inventory-II (BDI-II) to 537 participants (mean [standard deviation (SD)] age = 51 [9] years; female, 61%) enrolled in the Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) study. Leptin levels were examined as continuous log-transformed values.

Results: Participants with moderate to severe depression had higher levels of leptin (median [interquartile range] 37.7 [17.6-64.9] ng/mL) than those with mild depression (22.9 [7.0-57.9] ng/mL) or minimal to no depression (19.8 ng/mL [7.8-39.1], p = .003). Participants with moderate to severe depression had higher body mass index (BMI) than those with mild or minimal depression (mean [SD] = 33 [8] versus 31 [9] versus 29 [7] kg/m(2), p = .001). After multivariate adjustment for age, sex, race, smoking status, hypertension, diabetes, blood pressure, lipids, and C-reactive protein, the BDI-II score remained a significant predictor of leptin levels (β = 0.093, p = .01). Further adjustment for BMI eliminated the association between the BDI-II score and leptin (β = 0.03, p = .3). Adjusting for waist circumference in place of BMI revealed similar findings.

Conclusions: The association between depression and leptin seems to be mediated by increased adiposity in depressed individuals.