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 been found to be significantly lower in the blood of patients with major depression than in normal volunteers. The present study investigates plasma PEP activity in 25 major depressed, 10 manic, and 14 schizophrenic subjects versus 30 normal volunteers. It also examines the effects of antidepressants, valproate, and neuroleptic drugs on plasma PEP activity. PEP activity was significantly lower in major depressed subjects than in normal volunteers and in patients with mania and schizophrenia. In depressed subjects, plasma PEP activity was significantly increased during treatment with antidepressant drugs, such as fluoxetine. Plasma PEP activity was significantly increased in manic and schizophrenic subjects compared with normal volunteers. In manic subjects, short-term treatment with valproate had a significant suppressive effect on PEP activity. No significant effects of neuroleptics on PEP activity could be found in the schizophrenic patients. The results support the hypothesis that lower PEP activity could play a role in the pathophysiology of major depression, while increased PEP activity may be related to psychotic conditions, such as mania and schizophrenia.
Maes
M
M
University Department of Psychiatry, AZ Stuivenberg, Antwerp, Belgium.
Goossens
F
F
Scharpé
S
S
Calabrese
J
J
Desnyder
R
R
Meltzer
H Y
HY
D000339:Affect / Q000187:drug effects; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008134:Long-Term Care; D000085822:Prolyl Oligopeptidases; D012559:Schizophrenia / Q000188:drug therapy* / Q000201:enzymology; D012565:Schizophrenic Psychology; D012697:Serine Endopeptidases / Q000097:blood*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D014635:Valproic Acid; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases