Identification of altered dipeptidyl-peptidase activities as potential biomarkers for unipolar depression.
BACKGROUND
Changes in circulatory aminopeptidases [dipeptidyl-peptidase-IV (DPP-IV), Prolyl-oligopeptidase (POP) and Leucine aminopeptidase (LAP)] activities have been found to be associated with psychiatric illnesses and inflammatory diseases.


METHODS
The discriminatory indices of aminopeptidases activities were assessed by enzymatic assays in plasma samples from 240 unipolar depression (UD) patients and 264 matched controls. In addition the relationship between soluble and cellular DPP-IV activity was determined in plasma and blood cells from healthy subjects.


RESULTS
Greater than 95% of the plasma DPP-IV activity could be blocked by inhibitors, demonstrating the specificity of the assay. Also, DPP-IV protein and activity levels were strongly correlated. In contrast, only 50% of the membrane-bound activity in blood cells was inhibited, which suggested that other similar peptidases may be present in these cells. UD patients had decreased plasma levels of DPP-IV and POP activities compared to healthy controls with a concomitant increase in LAP activity. Finally, testing of the LAP/DPP-IV ratio resulted in good discrimination of UD patients from controls with an area under the curve-receiver operating characteristic of 0.70.


CONCLUSIONS
Further biological validation studies using different cohorts are warranted.


CONCLUSIONS
The finding that plasma DPP-IV activity was decreased and LAP activity was increased in UD patients suggests the potential value for testing the levels of these enzymes for improved classification of patients. In addition, the changes in these enzymes, suggests that the proteolytic maturation of their proneuropeptide and prohormone subtrates may also be affected in UD, resulting in altered production of the associated bioactive peptides.
Clinical Pharmacology Unit, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB2 2GG, UK.
Jingti
J
Deng
Clinical Pharmacology Unit, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB2 2GG, UK.
Jonathan R
JR
Lamb
Clinical Pharmacology Unit, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB2 2GG, UK.
Astrid P
AP
Mckeown
Clinical Pharmacology Unit, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB2 2GG, UK.
Sam
S
Miller
Medicines Research Centre, GlaxoSmithKline, Via Fleming 4, 37134 Verona, Italy.
Pierandrea
P
Muglia
Cambridge Centre for Neuropsychiatric Research, Department of Chemical Engineering and Biotechnology, Cambridge University, Tennis Court Road, Cambridge CB2 1QT, UK.
Paul C
PC
Guest
Cambridge Centre for Neuropsychiatric Research, Department of Chemical Engineering and Biotechnology, Cambridge University, Tennis Court Road, Cambridge CB2 1QT, UK.
Sabine
S
Bahn
Medicines Research Centre, GlaxoSmithKline, Via Fleming 4, 37134 Verona, Italy.
Enrico
E
Domenici
Clinical Pharmacology Unit, GlaxoSmithKline, Addenbrooke's Hospital, Cambridge CB2 2GG, UK; Cambridge Centre for Neuropsychiatric Research, Department of Chemical Engineering and Biotechnology, Cambridge University, Tennis Court Road, Cambridge CB2 1QT, UK. Electronic address: hr288@cam.ac.uk.
Hassan
H
Rahmoune
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D003866:Depressive Disorder / Q000097:blood / Q000201:enzymology*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007931:Leucyl Aminopeptidase / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D007931:Leucyl Aminopeptidase; D018819:Dipeptidyl Peptidase 4; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases
Aminopeptidase; Biomarkers; Peripheral blood mononuclear cells; Plasma; Unipolar depression