The present study, however, does not permit one to analyse these etiological factors. The genetically increased release could be due to a reduced activity of catechol-O-methyl-transferase

via a genetic polymorphism of this enzyme, which has been found to be associated with psychotic disorder combined with depression [McClay et al. 2006]. The increased correlation between NE and AVP could be due to an increased function of the Inhibitors,research,lifescience,medical excitatory α-1 receptor of the PVN [Al-Damluji, 1993]. Whether this would be due to a stress-induced sensitization mechanism analogous to the increase in NE transmission after a single administration of interleukin 1-α or amphetamine, in which sensitization of α-1 receptors for a stress condition may play a role [Jansen et al. 2003], is a matter for future studies. Since increased vasopressinergic activation may be a general mechanism in all depressive disorders, and subcategories are supposed

to be characterized by specific vasopressinergic mechanisms [Goekoop et Inhibitors,research,lifescience,medical al. 2010], we assume that increased α-1 receptor-mediated noradrenergic activation of AVP release is the specific mechanism involved in PSDEP. As α-1 receptor-mediated noradrenergic activity also induces a reduction of the pre-pulse-inhibition and an increase of conditioned avoidance behaviour, both being targets in animal Inhibitors,research,lifescience,medical models for antipsychotic drug development [see Wadenberg et al. 2000], the same noradrenergic mechanism could be involved in the increased activation of the HPA axis and in the production of psychotic symptoms. As a consequence, pharmacological treatment involving a blockade [Wadenberg Inhibitors,research,lifescience,medical et al. 2000] or downregulation [Subhash et al. 2003] of the α-1 receptor could be a specifically efficacious component of pharmacological treatment of PSDEP. The primary role supported by the present study for increased release of NE and increased α-1 receptor function in PSDEP implies that the meaning of previous findings in the field of

noradrenergic and dopaminergic function should be reconsidered. Previous findings in PSDEP are a reduction of dopamine-beta-hydroxylase Selleck JNK-IN-8 Inhibitors,research,lifescience,medical (DBH) activity and an increased concentration of plasma Survivin activity inhibition dopamine [Rothschild et al. 1987] compared with patients with non-PSDEP and normal controls. As far as dopamine release is concerned, evidence of a noradrenergic, α-1 mediated activation of that release from the ventral striatum has been found [Verheij and Cools, 2008]. Our present findings suggest that the previously found reduction of DBH activity in PSDEP could not be secondary to increased HPA axis function, as has been suggested [Cubells et al. 2002], but could actually depend more directly on the increased noradrenergic activation. Whether chronic downregulation of the synthesis of DBH occurs as an adaptation to a high tonic noradrenergic condition will have to be investigated in patients with PSDEP.