ALTERATIONS IN PLASMA PROLYL ENDOPEPTIDASE ACTIVITY IN DEPRESSION, MANIA, AND SCHIZOPHRENIA - EFFECTS OF ANTIDEPRESSANTS, MOOD STABILIZERS,AND ANTIPSYCHOTIC-DRUGS

The activity of prolyl endopeptidase (PEP), a serine proteinase, has b een found to be significantly lower in the blood of patients with majo r depression than in normal volunteers. The present study investigates plasma PEP activity in 25 major depressed, 10 manic, and 14 schizophr enic subjects versus 30 normal volunteers. It also examines the effect s of antidepressants, valproate, and neuroleptic drugs on plasma PEP a ctivity. PEP activity was significantly lower in major depressed subje cts than in normal volunteers and in patients with mania and schizophr enia. In depressed subjects, plasma PEP activity was significantly inc reased during treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was significantly increased in manic and schizoph renic subjects compared with normal volunteers. In manic subjects, sho rt-term treatment with valproate had a significant suppressive effect on PEP activity. No significant effects of neuroleptics on PEP activit y could be found in the schizophrenic patients. The results support th e hypothesis that lower PEP activity could play a role in the pathophy siology of major depression, while increased PEP activity may be relat ed to psychotic conditions, such as mania and schizophrenia.