期刊
JOURNAL OF PSYCHIATRIC RESEARCH
卷 47, 期 5, 页码 657-663出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jpsychires.2013.01.009
关键词
Schizophrenia; Biomarker; Enzyme activity; Oligopeptidase; Plasma; Neuropeptide
类别
资金
- Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP) [2008/57336-2, 2010/01394-4, 2011/50740-5, 2009/17726-9, 2003/00817-5]
- National Council of Technological and Scientific Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq) [477760/2010-4, 557753/2010-4, 508113/2010-5]
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
- FAPESP [2008/57336-2]
- CNPq (National Counsel of Technological and Scientific Development)
- CNPq
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
- CAPES
- Fullbright
- FAP/UNIFESP
- Astra Zeneca
- Bristol
- Janssen
- Lundbeck
- Jansse
- Eli Lilly
- Novartis
- Roche
- Fundacao Safra
- Fundacao ABADS
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/50740-5, 09/17726-9] Funding Source: FAPESP
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 Ltd. All rights reserved.
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