Plasma peptidases as prognostic biomarkers in patients with first-episode psychosis

Ainhoa Fernández-Atucha1

Enrique Echevarría2

Gorka Larrinaga3

Javier Gil4

Mónica Martínez-Cengotitabengoa5

Ana M. González-Pinto6

Jon Irazusta3

Jesús Seco

1Dpt. Physiology, Fac. Medicine, University of the Basque Country, Barrio Sarriena, s/n 48940, Leioa – Bizkaia, Spain. Tel.: +34 946 01 3427.

2Dpt. Physiology, Fac. Pharmacy, University of the Basque Country, Paseo de la Universidad 7, 01006 Vitoria, Spain. Tel.: +34 945 013035.

3Dpt. Physiology, Fac. Medicine, University of the Basque Country, Barrio Sarriena, s/n 48940, Leioa – Bizkaia, Spain. Tel.: +34 946 01 2837, +34 946 01 2064.

4Dpt. Physiology, Fac. Medicine, University of the Basque Country, Barrio Sarriena, s/n 48940, Leioa – Bizkaia, Spain. Tel.: +34 946 01 5657, +34 946 01 2182.

5International Mood Disorders Research Centre, Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Hospital Universitario de Alava, Spain; National Distance University (UNED), Spain; c/ Olaguibel, 29, 01004 Vitoria-Gasteiz, Álava, Spain. Tel.: +34 945007769; fax: +34 945007764.

6International Mood Disorders Research Centre, Centro de Investigación Biomédica en Red en Salud Mental (CIBERSAM), Hospital Santiago Apóstol, University of the Basque Country, Vitoria, Spain; c/ Olaguibel, 29, 01004 Vitoria-Gasteiz, Álava, Spain. Tel.: +34 945007769; fax: +34 945007764.

7Visiting Researcher and Professor University of the Basque Country, Spain.

Received: April 10, 2014; Received in revised form: January 28, 2015; Accepted: April 4, 2015; Published Online: April 30, 2015

Publication stage: In Press Corrected Proof

DOI: http://dx.doi.org/10.1016/j.psychres.2015.04.027

Article Info

Abstract

The plasma activity of nine aminopeptidases was monitored over a year in first-episode psychotic patients. We observed significant differences in aminopeptidase B (APB), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPPIV), but not in puromycin-sensitive aminopeptidase (PSA), prolyl endopeptidase (PEP), cysteine aminopeptidase (Cys-AP), aspartate aminopeptidase (Asp-AP), glutamate aminopeptidase (Glu) or piroglutamate aminopeptidase (PGI) in these patients compared to controls, and also a progressive increase in plasma activity, correlated to changes in scores on clinical scales, Global Assessment of Functioning scale (GAF) and Hamilton Depression Rating Scale (HDRS), at 1 month of follow-up. At 1 month after diagnosis, the median score obtained by patients on the GAF was negatively associated with the plasma activity of APB and PEP measured at the beginning of the psychotic episode, indicating a role as a negative prognostic factor that can predict psychiatric symptomatology. In the case of HDRS, scores at 1 month after diagnosis were found to be positively associated with the initial plasma activity of DPPIV, APN and PSA, indicating that their initial elevation is a negative prognostic factor that can predict subsequent depressive symptomatology. Taken together, these results suggest a pathophysiological involvement of plasma peptidases and indicate that aminopeptidase activity can predict the course of first-episode psychosis patients, acting as a prognostic indicator.