17,18 Subjects with MDD are prone to increased central fat distribution.19,20 Although the exact mechanisms are not known, alterations of the hypothalamicpituitary-adrenal (HPA) axis secondary to depression, such as increased 24-hour plasma cortisol concentration,21,22 could contribute to central obesity23,24 Augmented coagulability due to increased concentration or activity of coagulation factors25,26 and PAI-127,28 has in fact been reported in other

hypercortisolemic states, such as Cushing’s syndrome, and in patients treated with glucocorticoids. We tested whether MDD was associated with changes in the prothrombotic factors, PAI-1 and fVIII, as well as with altered body fat Inhibitors,research,lifescience,medical distribution, which may lead to hypercoagulability, and subsequent cardiovascular diseases.29 We also assessed whether these factors correlate with the severity of depression Inhibitors,research,lifescience,medical and cortisol concentration. PAI-1 concentration (Figure 3) and fVIII activity were significantly higher at 0800 h than 2000 h in both the MDD and control groups, confirming the existence of circadian rhythmicity. Both PAI-1 and fVIII were significantly

higher at 2000 h in women with MDD than in controls. Figure 3. Plasminogen activator-1 (PAI1). PAI-1 concentrations exhibit Inhibitors,research,lifescience,medical an exponential distribution both in subjects with MDD and controls. Panel A: 0800 h PAI-1 concentration. Panel B: 2000 h PAI-1 concentration. Reproduced from ref 29: Eskandari F, Mistry S, Martinez … Women with MDD had higher PAI-1 concentration and fVIII activity and more abdominal fat than healthy Inhibitors,research,lifescience,medical controls. Increased central body fat in association with symptoms of depression and anxiety has already been reported in large epidemiological studies of men and women.19,20 The increase in prothrombotic factors in young women with MDD, reported for the first time in the POWER Study, is likely to be of clinical importance. These abnormalities persisted after correction for body weight, and were even more evident in the subset of subjects individually matched for age and BMI, suggesting that Inhibitors,research,lifescience,medical the association

between depression and these factors was specific. PAI-1 concentrations were similar to those reported in the subjects who later Mcl-1 apoptosis developed diabetes mellitus most in a large prospective study30 Similarly, increased risk of diabetes mellitus has been reported in subjects with increased fVIII activity.31 Abnormal plasma C-reactive protein levels C-reactive protein (CRP), a nonspecific marker of inflammation, is regarded as a risk factor for cardiovascular events. Recently, it has been proposed to include CRP as a clinical criterion for the metabolic syndrome as well.32 CRP is being proposed as a marker clinically useful for following prospectively subjects; however, only limited information on its variability over time exists. The reported variability over a week is approximately 30% to 50%, underlining the importance of performing serial sampling, especially if the values are in a high range.