Low 24-hour adiponectin and high nocturnal leptin concentrations in a case-control study of community-dwelling premenopausal women with major depressive disorder: the Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression (POWER) study

Abstract

Objective: Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipocytokine with anti-inflammatory and antiatherogenic effects. Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were (1) to establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; (2) to assess whether there is a relationship between adiponectin and MDD; and (3) to explore the temporal relationships among adiponectin, leptin, corticotropin, and cortisol secretion.

Method: We conducted a case-control study of community-dwelling premenopausal women with DSM-IV MDD (n = 23) and age- and body mass index (BMI)-matched control subjects (n = 23). Main outcome measures were circulating concentrations of adiponectin, leptin, corticotropin, and cortisol measured hourly for 24 hours. Subjects were recruited from July 1, 2001, to February 28, 2003.

Results: Women with MDD had approximately 30% lower mean 24-hour concentration of adiponectin than did control subjects. Adiponectin concentration was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, mean nocturnal leptin concentration was higher in the MDD versus control groups. Mean leptin concentration was inversely related to cortisol and adiponectin concentrations, both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between corticotropin and cortisol concentrations was stronger in women with MDD than in control subjects, a finding consistent with hypothalamic-pituitary-adrenal (HPA) axis activation in MDD.

Conclusions: In premenopausal women with MDD, reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis.

Fig. 1

Fig. 1 upper panel depicts adiponectin concentrations. In both groups, adiponectin exhibited a circadian variation characterized by slightly higher values during early afternoon with a peak around 1400h. Adiponectin remained lower in women with MDD over 24h. 0800h and 24h mean adiponectin was significantly lower in women with MDD compared to controls (0800h P adjusted for weight =0.0053; mean 24h P adjusted for weight =0.042; analysis of covariance). Error bars represent SEM. Fig. 1 lower panel depicts leptin levels. In both groups, leptin exhibited a circadian variation characterized by a nocturnal zenith around 0200h and a nadir around 1000h. Leptin remained higher in women with MDD over 24h. 0800h and 24h mean leptin was significantly higher in women with MDD compared to controls (0800h P adjusted for weight =0.010; mean 24h P adjusted for weight =0.021; analysis of covariance). Mean nocturnal (2000h-0400h) leptin, was greater in women with MDD than controls (21.05 ± 0.91 ng/ml vs 16.10 ± 0.98 ng/ml, respectively, P<0.001). Error bars represent SEM.

Fig. 2

Fig. 2 upper panel depicts ACTH concentrations collected hourly for 24h starting at 0800h in women with MDD (solid squares) and in controls (open circles) individually age and BMI-matched. Lights were off between 2300h-0700h, as indicated by a solid horizontal line. In both groups, ACTH exhibited similar circadian rhythm with similar time of peak and nadir. 0800h ACTH was significantly higher in women with MDD than controls. Mean nocturnal (0100h - 0500h) ACTH was lower in women with MDD than controls (P=0.023). Error bars represent SEM. Fig. 2 lower panel depicts cortisol concentrations. In both groups, cortisol exhibited similar circadian rhythm and no difference in peak values. Error bars represent SEM.