LOWER SERUM PROLYL ENDOPEPTIDASE ENZYME-ACTIVITY IN MAJOR DEPRESSION - FURTHER EVIDENCE THAT PEPTIDASES PLAY A ROLE IN THE PATHOPHYSIOLOGY OF DEPRESSION

Prolyl endopeptidase (PEP) is a serine proteinase, which may cleave pe ptides that are involved in the pathophysiology of major depression, s uch as arginine vasopressin, beta-endorphin, luteinizing hormone-relea sing hormone, thyrotropin-releasing hormone, and maybe corticotropin-r eleasing hormone. PEP may be involved in activation of cell-mediated i mmunity, autoimmune and inflammatory responses, which repeatedly occur in severe depression. The present study investigates serum PEP activi ty in 33 normal controls, 16 minor, 14 simple major, and 18 melancholi c depressed subjects. Pre-dexamethasone and post-dexamethasone (DST) i ntact adrenocorticotropic hormone (ACTH) and cortisol values were dete rmined in 33 depressed subjects. Serum PEP activity was significantly lower in depressed subjects compared to normal controls and in melanch olic depressed subjects compared to minor and simple major depressed s ubjects. Up to 61.1% of the melancholic patients had serum PEP activit ies below the mean PEP values of normal controls minus two SDs. In the depressed study group, significant negative correlations between seru m PEP activity and severity of illness, post-DST cortisol, and ACTH va lues 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.