Higher serum prolyl endopeptidase activity in patients with post-traumatic stress disorder

Background: It is reported that psychiatric disorders, such as depression and schizophrenia, are associated with changes in serum activity of prolyl endopeptidase (EC 3.4.21.26), a cytosolic endopeptidase, which cleaves peptide bonds on the carboxylside of proline in proteins of relatively small molecular mass. Aims and methods: The aims of the present study were to examine serum PEP activity in patients with post-traumatic stress disorder (PTSD) versus healthy volunteers. PEP activity has been determined by a fluorimetric assay. Results: Serum PEP activity was significantly higher in patients with PTSD than in normal volunteers. Serum PEP activity was significantly higher in patients with PTSD and concurrent major depression than in patients with PTSD without major depression. In PTSD patients, there were no significant correlations between serum PEP activity and severity of PTSD symptoms. Conclusions: The results show that PTSD and, in particular, PTSD with concurrent major depression is associated with increased activity of PEP. Relevance: these results may be of importance for the (i) neuroendocrine pathophysiology of PTSD since PEP degrades neuropeptides, such as arginine vasopressin (AVP) and thyrotropin releasing hormone (TRH); and (ii) etiology of PTSD, since PEP degrades behaviorally active neuropeptides, such as AVP, TRH, oxytocin, neurotensin and substance P, which play a key role in positive reinforcement, social interactions, emotions and stress responsivity.