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PLoS One. 2014 Feb 3;9(2):e87686. doi: 10.1371/journal.pone.0087686. eCollection 2014.

PRODH polymorphisms, cortical volumes and thickness in schizophrenia.

Author information

1
Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; LiNC - Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil.
2
Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil.
3
LiNC - Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.
4
Disciplina de Genética e Reproducao Humana, Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina do ABC (FMABC), Santo Andre, Sao Paulo, Brazil.
5
Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.
6
Laboratório de Genética Humana e Médica, Universidade Federal do Pará (UFPA), Belém, Pará, Brazil.
7
LiNC - Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil.
8
LiNC - Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil.
9
Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; LiNC - Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.

Abstract

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. The study included 179 controls paired by age and gender. The samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. In summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.

PMID:
24498354
PMCID:
PMC3912045
DOI:
10.1371/journal.pone.0087686
[Indexed for MEDLINE]
Free PMC Article

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