To our knowledge, this is the first study suggesting a relation between serum levels of VEGF and severity of depression. In the present study, in line with several studies [Deuschle et al. 1996; Moosa et al. 2003; Kauffman et al. 2005], there was no significant difference in serum leptin levels between the MDD patients and controls. Inhibitors,research,lifescience,medical No relation was found between leptin levels and severity of depression, suicidality and recurrence of depressive episodes. We think that our data about leptin levels are noteworthy considering that the study had a

very homogeneous subgroup of depression with a predominantly biological etiology. It is surprising that there was no significant difference between serum Inhibitors,research,lifescience,medical cortisol levels of patients and controls as approximately 50% of depressed patients exhibit dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which results in sustained elevations in cortisol levels [Gold and Chrousos, 2002; Swaab et al. 2005]. Elevation of basal cortisol levels [Belanoff et al. 2001], and nonsuppression on the dexamethasone suppression test [Nelson and Davis, 1997], were most clearly evident in psychotic depression. None of our patients had any psychotic symptoms. Moreover, hypercortisolaemia

has not been a stable finding in all studies and a SB202190 dysfunction of the HPA axis has been proposed as an alternative hypothesis [Peeters et al. 2004]. Inhibitors,research,lifescience,medical Peeters and colleagues suggested that erratic cortisol secretion may be a more characteristic feature of HPA-axis dysregulation than hypercortisolism, especially in outpatient populations [Peeters Inhibitors,research,lifescience,medical et al. 2004]. Assies and colleagues found no difference between the cortisol levels of depressed patients and controls and indicated that dehydroepiandrosterone-sulphate Inhibitors,research,lifescience,medical may be a more important indicator of depression [Assies et al. 2004]. Michopoulos and colleagues found that depressive patients had normal cortisol blood levels and there was no significant difference between

melancholic and nonmelancholic depressive patients [Michopoulos et al. 2008]. Glucocorticoids play a critical role in mediating Sitaxentan stress-induced downregulation of BDNF in the hippocampus [Schmidt and Duman, 2007]. Thus, our finding that there is no significant difference between serum BDNF levels of patients and controls is concordant with the finding that there is also no significant difference between the cortisol levels of the two groups. One of the limitations of the study was the absence of a control group composed of other types of MDDs. One might consider the selection of serum instead of plasma as the specimen for BDNF as a limitation, however, as mentioned above, data about BDNF levels in serum or plasma of depressive patients are conflicting. Furthermore, it was reported that plasma BDNF has shown high interindividual variability [Piccinni et al. 2009].