Leptin in Depressed Women: Cross-sectional and Longitudinal Data from an Epidemiologic Study

Background: There is conflicting evidence regarding levels of leptin in depression. In this study we aimed to investigate the relationship between serum leptin level and depression in a community sample of women using both cross-sectional and longitudinal data.

Methods: From among 510 women aged 20-78 yr, 83 were identified with a lifetime history of major depressive disorder or dysthymia, ascertained using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). Serum leptin levels were measured by radioimmunoassay. Medication use and lifestyle were self-reported and body mass index (BMI) determined from measures of height and weight.

Results: Using multiple linear regression, serum leptin levels were greater among women with a lifetime history of depression compared to women without any history of depression, independent of BMI. Adjusted geometric mean values of serum leptin were 16.37 (95%CI 14.70-18.23) ng/mL for depressed and 14.46 (95%CI 13.79-15.16) ng/mL for non-depressed women (P=0.039). The hazard ratio (HR) for a de novo depressive disorder over five years increased 2.56-fold for each standard deviation increase in log-transformed serum leptin among non-smokers and this was not explained by differences in BMI, medications or other lifestyle factors (HR=2.56, 95%CI 1.52-4.30). No association was observed for smokers.

Limitations: There is potential for unrecognised confounding, recall bias and transient changes in body composition.

Conclusion: Women with a lifetime history of depression have elevated levels of serum leptin, and elevated serum leptin predicts subsequent development of a depressive disorder.