1999]. In another series of investigations PSDEP appeared to relate to a global hierarchic dimension of psychopathology that comprises depressive symptoms at the lowest level of the hierarchy, specific neurotic symptoms at a higher level and psychotic symptoms at the highest level [Surtees and Kendell, 1979]. The symptoms of the nonpsychotic part of this hierarchy correspond to Inhibitors,research,lifescience,medical the symptoms found in the hierarchic global dimension of Emotional Dysregulation [Goekoop and Zwinderman, 1994]. These findings support the usefulness of a

multidimensional assessment of nonpsychotic psychopathology to control for relations with PSDEP that could be explained by relations with the nonpsychotic admixture of that subcategory. We also searched for potentially confounding effects on the concentration of plasma NE of current antipsychotic, antidepressant Inhibitors,research,lifescience,medical and benzodiazepine treatment and their dosages, type of antidepressant drug, smoking habit, sex, age, duration of the disease and inpatient or outpatient treatment. Smoking may immediately affect Inhibitors,research,lifescience,medical peripheral sympathetic activity [Grassi et al. 1994], and long-term smoking may increase the NE concentration [Christensen and Jensen, 1995].

Long-term treatment with a tricyclic drug, at least 100 mg, has been found to increase plasma NE concentration [Veith et al. 1994], while plasma NE has been found to be nonsignificantly decreased in patients with major depressive disorder treated with selective serotonin reuptake inhibitors (SSRIs) [Barton et al. 2007]. As far as we know, this method of analysing the plasma NE concentration as a potential biomarker of PSDEP, controlling for several confounding effects, has

not been used before. Inhibitors,research,lifescience,medical Since in our previous study [Goekoop et al. 2011] we did not analyse the effect of antidepressant drug type, we reanalysed the correlation between plasma NE and AVP in PSDEP. Antipsychotic Inhibitors,research,lifescience,medical drug dose was used as an additional confounder in these analyses as it correlates positively with the concentration of plasma AVP [Goekoop et al. 2006]. In summary, we hypothesize the plasma concentration of NE to be Proteases inhibitor increased in PSDEP compared with non-PSDEP, and the correlation between plasma NE and plasma AVP still to be present when accounting for several potentially confounding effects. Methods below Subjects We reanalysed the data from the same patient sample in which we previously found support for the HAR and ANA subcategories of depression [Goekoop and Wiegant, 2009] and a general vasopressinergic theory of depression [Goekoop et al. 2010]. All patients fulfilled DSM-IV criteria [American Psychiatric Association, 1994] for major depression and scored at least 20 on the MADRS [Montgomery and Asberg, 1979]. The 78 patients with complete NE data were selected from 89 patients who were initially included, 9 with PSDEP and 69 with non-PSDEP.