Reports of serum leptin levels in depressed subjects are conflicting, with studies finding either no differences, lower levels in depressed men, elevated levels in depressed men and women, or elevated levels only in depressed women. Adiponectin was first reported as an adipocyte secretory protein in 1995, but only recently has its physiology been investigated.48 Plasma adiponectin concentrations

are about two to three times greater than those of most other hormones, and its concentrations, unlike those of other adipocytokines, are inversely related to adiposity. Adiponectin receptors (AdipoR1 and R2) have been identified in the periphery Inhibitors,research,lifescience,medical and CNS. AdipoR1 is abundant in skeletal muscle and AdipoR2 exists primarily in the liver.46 AdipoR1 and AdipoR2 are also present in the paraventricular nucleus of the hypothalamus, amygdala, area postrema and, diffusely, in the periventricular areas and cortex. While leptin’s rhythmicity Inhibitors,research,lifescience,medical is well described, adiponectin’s 24-hour secretory SRT1720 profile is not well known. Adiponectin exhibits diurnal and ultradian rhythms Inhibitors,research,lifescience,medical in normal-weight men.49 Circulating concentrations of adiponectin have been reported in depressed

patients, but only at single time points. In some such studies, adiponectin was lower in newly diagnosed and drug-naïve MDD subjects, and was inversely related to depression severity.50 However, in others, there was no significant relationship between single adiponectin measurements and depressive symptoms.51 To date, 24-hour secretory profiles Inhibitors,research,lifescience,medical of adiponectin have not been described in MDD patients. Because MDD subjects have a higher CVD prevalence, and reduced adiponectin is associated with negative health consequences, Inhibitors,research,lifescience,medical adiponectin rhythmicity in patients

with depression is of interest. The relationship of adiponectin to the HPA axis and leptin also remains unknown in MDD subjects. In a satellite study47 we aimed to establish: (i) whether women with MDD have decreased circulating concentrations of adiponectin and/or disruption of adiponectin secretory rhythmicity; (ii) the relationship of adiponectin and leptin secretion with depression; (iii) the temporal correlations among circadian concentrations Cell press of adiponectin, leptin, ACTH, and cortisol. From the whole POWER sample, we individually matched 23 consecutively studied women with MDD with 23 control subjects, based on age ±3.0 years and BMI ±2.0 kg/m2. In control subjects, diurnal fluctuation in adiponectin was about 30% (Figure 5, upper panel). Adiponectin was higher during the day, with a zenith around 1430 h, an initial fall around 1600 h, a further decline after 2300 h and then another increase at about 0300 h. Women with MDD exhibited similar adiponectin rhythmicity. Mean adiponectin concentrations were about 25% lower at all 24-h time points in women in the MDD versus control group.