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Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders

Published online by Cambridge University Press:  23 March 2020

G. Mezquida
Barcelona clinic schizophrenia unit (BCSU), Institut clínic de neurociències (ICN), hospital clinic de Barcelona, Barcelona, Spain
R. Penadés
Barcelona clinic schizophrenia unit (BCSU), Institut clínic de neurociències (ICN), hospital clinic de Barcelona, Barcelona, Spain Department of psychiatry and clinical psychobiology, university of Barcelona, Barcelona, Spain Institut d’investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain
B. Cabrera
Barcelona clinic schizophrenia unit (BCSU), Institut clínic de neurociències (ICN), hospital clinic de Barcelona, Barcelona, Spain Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain
G. Savulich
Department of psychiatry, university of Cambridge, Cambridge, UK
A. Lobo
Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain Instituto de Investigación Sanitaria de Aragón (IIS Aragón), university of Zaragoza, Zaragoza, Spain
A. González-Pinto
Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain Araba university hospital, Bioaraba research institute, Araba, Spain University of the Basque Country (UPV-EHU), Leioa, Spain
M.J. Penzol
Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain Child and adolescent psychiatry department, hospital general universitario Gregorio Marañón, school of medicine, universidad Complutense, Madrid, Spain
I. Corripio
Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain Department of psychiatry, institut d’investigació Biomèdica-Sant Pau (IIB-SANT PAU), hospital de la Santa Creu i Sant Pau, Barcelona, Spain Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
E. Fernandez-Egea
Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain Behavioural and clinical neuroscience institute, university of Cambridge, Cambridge, UK
P. Gassó
Institut d’investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Department of pathological anatomy, pharmacology and microbiology, university of Barcelona, Barcelona, Spain
M.J. Cuesta
Department of psychiatry, Complejo Hospitalario de Navarra, Navarra, Spain IdiSNA, Navarra institute for health research, Navarra, Spain
M. Bernardo*
Barcelona clinic schizophrenia unit (BCSU), Institut clínic de neurociències (ICN), hospital clinic de Barcelona, Barcelona, Spain Department of psychiatry and clinical psychobiology, university of Barcelona, Barcelona, Spain Institut d’investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Biomedical research networking centre in mental health (CIBERSAM), Barcelona, Spain
*Corresponding author. Barcelona clinic schizophrenia unit, hospital clinic of Barcelona, 170, Villarroel, 08036 Barcelona, Spain. Tel.: +34932275400x3142; fax: +34932275548. E-mail Bernardo).
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A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients.


Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity.


There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele.


The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum.

Original article
Copyright © Elsevier Masson SAS 2016

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