Lower serum prolyl endopeptidase enzyme activity in major depression: Further evidence that peptidases play a role in the pathophysiology of depression

Michaël Maes*, Filip Goossens, Simon Scharpé, Herbert Y. Meltzer, Peter D'Hondt, Paul Cosyns

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Prolyl endopeptidase (PEP) is a serine proteinase, which may cleave peptides that are involved in the pathophysiology of major depression, such as arginine vasopressin, β-endorphin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and maybe corticotropin-releasing hormone. PEP may be involved in activation of cell-mediated immunity, autoimmune and inflammatory responses, which repeatedly occur in severe depression. The present study investigates serum PEP activity in 33 normal controls, 16 minor, 14 simple major, and 18 melancholic depressed subjects. Pre-dexamethasone and post-dexamethasone (DST) intact adrenocorticotropic hormone (ACTH) and cortisol values were determined in 33 depressed subjects. Serum PEP activity was siginificantly lower in depressed subjects compared to normal controls and in melancholic depressed subjects compared to minor and simple major depressed subjects. Up to 61.1% of the melancholic patients had serum PEP activities below the mean PEP values of normal controls minus two SDs. In the depressed study group, significant negative correlations between serum PEP activity and severity of illness, post-DST cortisol, and ACTH values were observed. There was a trend toward higher serum PEP activity with increasing age. It is hypothesized that lower serum PEP activity, and lower serum activity of other peptidases, may play a role in the neuroendocrine and immune pathophysiology of major depression.

Original languageEnglish (US)
Pages (from-to)545-552
Number of pages8
JournalBiological psychiatry
Volume35
Issue number8
DOIs
StatePublished - Apr 15 1994

Keywords

  • Depression
  • dipeptidyl peptidase IV
  • hypothalamic-pituitary-adrenal axis
  • peptidases
  • prolyl endopeptidase
  • proteinases
  • psychoimmunology

ASJC Scopus subject areas

  • Biological Psychiatry

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