Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia: effects of antidepressants and antipsychotic drugs

Abstract

Maes M, De Meester I, Scharpé S, Desnyder R, Ranjan R, Meltzer HY. Alterations in plasma dipeptidyl peptidase IV enzyme activity in depression and schizophrenia effects of antidepressants and antipsychotic drugs. Acta Psychiatr Scand 1996: 93: 1–8. ©Munksgaard 1996. Recently, our laboratory reported that the activity of dipeptidyl‐peptidase IV (DPP IV) was significantly lower in the peripheral blood of major depressed patients than in normal controls. The present study examines plasma DPP IV activity in 43 major depressed and 13 schizophrenic subjects versus 21 normal controls and the effects of antidepressants and ntipsychotic drugs on plasma DPP IV activity. DPP IV activity was significantly lower in major depressed subjects than in normal controls and schizophrenic subjects. There was a trend towards higher DPP IV activity in schizophrenic patients than in normal controls. There were no significant effects of antidepressants or neuroleptics on plasma DPP IV activity in depressed and schizophrenic patients, respectively. There were no significant relationships between plasma DPP IV activity and plasma cortisol or immune‐inflammatory markers, such as serum interleukin‐6 (IL‐6) or soluble IL‐2 receptor. A significant and positive correlation was found between plasma DPP IV and prolyl endopeptidase (PEP) enzyme activity in the study group as a whole and in schizophrenic subjects. The results support the hypothesis that lower and higher plasma DPP IV activities are trait markers of major depression and schizophrenia, respectively. It is concluded that alterations in the enzyme activity of peptidases, such as DPP IV and PEP, play a role in the pathophysiology of major depression and schizophrenia.

The Therapeutic Potential of Inhibitors of Dipeptidyl Peptidase IV (DPP IV) and Related Proline-Specific Dipeptidyl Aminopeptidases

“…Moreover, changes in DPP IV activity have been reported in sera from patients with psychiatric or psychosomatic diseases [71]. Patients with major depression and schizophrenia show a decrease in serum DPP IV activity [227,228,229,230]. Patients with anorexia nervosa show an increase in DPP IV serum activity [231,232,233].…”

A guardian angel: the involvement of dipeptidyl peptidase IV in psychoneuroendocrine function, nutrition and immune defence

“…Plas- [79] in serum on lymphocytes Systemic lupus erythematosus [67] in serum in all patients No data available in lymphocytes of patients with active disease Rheumatoid arthritis [69] in synovial fluid No data available Pregnancy [80] in serum No data available AIDS [78] Normal no. of DPP IV-positive lymphocytes Major depression [81] in serum No data available Schizophrenia [82] in serum No data available Fibromyalgia [83] Normal No data available Anorexia nervosa [84] in serum no. of DPP IV-positive lymphocytes minogen and streptokinase have both been shown to bind to DPP IV expressed on rheumatoid synovial fibroblasts [72].…”

“…Phase-shift in the endogenous circadian rhythm of thalamic neurons ; blood pressure recovery during endotoxic and haemorrhagic shock [90] Substrate P [91] Degradation to a more potent heptapeptide More profound effect on transmission of nociception, depression of blood pressure and relaxation of smooth muscle serum DPP IV activity as compared with healthy controls, a change that was apparently independent of anti-depressants and anti-psychotic drugs [82].…”

Azetidine-Based Inhibitors of Dipeptidyl Peptidase IV (DPP IV)

“…A proline residue in the penultimate position of the Nterminus is cleaved in each of these endogenous substrates, accounting for the design of many of the substrate-based inhibitors [5]. The inhibition of DPP IV and prevention of the degradation of these substrates can ultimately produce pharmacological effects in therapeutic areas as wide ranging as diabetes [6], pain [7], cognition enhancement [8] and schizophrenia [9].…”