Plasma Ndel1 enzyme activity is reduced in patients with schizophrenia - A potential biomarker?

Plasma Ndel1 enzyme activity is reduced in patients with schizophrenia - A potential biomarker?

Author Gadelha, Ary Autor UNIFESP Google Scholar
Machado, Mauricio F. M. Autor UNIFESP Google Scholar
Yonamine, Camila M. Autor UNIFESP Google Scholar
Sato, Joao R. Google Scholar
Juliano, Maria A. Autor UNIFESP Google Scholar
Oliveira, Vitor Autor UNIFESP Google Scholar
Bressan, Rodrigo A. Autor UNIFESP Google Scholar
Hayashi, Mirian A. F. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract Ndel1 oligopeptidase interacts with schizophrenia (SCZ) risk gene product DISCI and mediates several functions related to neurite outgrowth and neuronal migration. Ndel1 also hydrolyzes neuropeptides previously implicated in SCZ, namely neurotensin and bradykinin. Herein, we compared the plasma Ndel1 enzyme activity of 92 SCZ patients and 96 healthy controls (HCs). Ndel1 enzyme activity was determined by fluorimetric measurements of the FRET peptide substrate Abz-GFSPFRQ-EDDnp hydrolysis rate. A 31% lower mean value for Ndel1 activity was observed in SCZ patients compared to HCs (Student's t = 4.36; p < 0.001; Cohen's d = 0.64). the area under the curve (AUC) for the Receiver Operating Characteristic (ROC) curve for Ndel1 enzyme activity and SCZ/HCs status as outcome was 0.70. Treatment-resistant (TR) SCZ patients were shown to present a significantly lower Ndel1 activity compared to non-TR (NTR) patients by t-test analysis (t = 2.25; p = 0.027). A lower enzymatic activity was significantly associated with both NTR (p = 0.002; B = 1.19; OR = 3.29; CI 95% 1.57-6.88) and TR patients (p < 0.001; B = 2.27; OR = 9.64; CI 95% 4.12-22.54). No correlation between Ndel1 enzyme activity and antipsychotic dose, nicotine dependence, and body mass index was observed. This study is the first to show differences in Ndel1 activity in SCZ patients compared to HCs, besides with a significant lower activity for TR patients compared to NTR patients. Our findings support the Ndel1 enzyme activity implications to clinical practice in terms of diagnosis and drug treatment of SCZ.Objective of the study: To compare the Ndel1 enzyme activity levels of schizophrenia (SCZ) patients and healthy controls (HCs) and to correlate these values with the clinical profile and response to treatment by measuring the Ndel1 enzyme activity in human plasma. (C) 2013 Elsevier B.V. All rights reserved.
Keywords Schizophrenia
Biomarker
Enzyme activity
Oligopeptidase
Plasma
Neuropeptide
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fullbright
FAP/UNIFESP
Astra Zeneca
Bristol
Janssen
Lundbeck
Jansse
Eli Lilly
Novartis
Roche
Fundacao Safra
Fundacao ABADS
Grant number FAPESP: 2008/57336-2
FAPESP: 2010/01394-4
FAPESP: 2011/50740-5
FAPESP: 2009/17726-9
FAPESP: 2003/00817-5
CNPq: 477760/2010-4
CNPq: 557753/2010-4
CNPq: 508113/2010-5
Date 2013-05-01
Published in Journal of Psychiatric Research. Oxford: Pergamon-Elsevier B.V., v. 47, n. 5, p. 657-663, 2013.
ISSN 0022-3956 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 657-663
Origin http://dx.doi.org/10.1016/j.jpsychires.2013.01.009
Access rights Closed access
Type Article
Web of Science ID WOS:000317447400015
URI http://repositorio.unifesp.br/handle/11600/36294

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