PMID- 24498354 OWN - NLM STAT- MEDLINE DCOM- 20141203 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 2 DP - 2014 TI - PRODH polymorphisms, cortical volumes and thickness in schizophrenia. PG - e87686 LID - 10.1371/journal.pone.0087686 [doi] LID - e87686 AB - 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. FAU - Ota, Vanessa K AU - Ota VK AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Bellucco, Fernanda T AU - Bellucco FT AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Gadelha, Ary AU - Gadelha A AD - LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Santoro, Marcos L AU - Santoro ML AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Noto, Cristiano AU - Noto C AD - LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Christofolini, Denise M AU - Christofolini DM AD - Disciplina de Genetica e Reproducao Humana, Departamento de Ginecologia e Obstetricia, Faculdade de Medicina do ABC (FMABC), Santo Andre, Sao Paulo, Brazil. FAU - Assuncao, Idaiane B AU - Assuncao IB AD - Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Yamada, Karen M AU - Yamada KM AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Ribeiro-dos-Santos, Andrea K AU - Ribeiro-dos-Santos AK AD - Laboratorio de Genetica Humana e Medica, Universidade Federal do Para (UFPA), Belem, Para, Brazil. FAU - Santos, Sidney AU - Santos S AD - Laboratorio de Genetica Humana e Medica, Universidade Federal do Para (UFPA), Belem, Para, Brazil. FAU - Mari, Jair J AU - Mari JJ AD - Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Smith, Marilia A C AU - Smith MA AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Melaragno, Maria I AU - Melaragno MI AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Bressan, Rodrigo A AU - Bressan RA AD - LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. FAU - Sato, Joao R AU - Sato JR AD - LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil. FAU - Jackowski, Andrea P AU - Jackowski AP AD - LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. FAU - Belangero, Sintia I AU - Belangero SI AD - Disciplina de Genetica, Departamento de Morfologia e Genetica, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; LiNC - Laboratorio Interdisciplinar de Neurociencias Clinicas, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil ; Departamento de Psiquiatria, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140203 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - EC 1.5.3.- (Proline Oxidase) RN - EC 1.5.5.2 (PRODH protein, human) SB - IM MH - Adult MH - Cerebral Cortex/*metabolism/pathology MH - DNA Mutational Analysis MH - Diagnostic and Statistical Manual of Mental Disorders MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease/*genetics MH - Genotype MH - Humans MH - Linkage Disequilibrium MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Polymerase Chain Reaction MH - Polymorphism, Restriction Fragment Length MH - *Polymorphism, Single Nucleotide MH - Proline Oxidase/*genetics MH - Psychiatric Status Rating Scales MH - Schizophrenia/diagnosis/enzymology/*genetics PMC - PMC3912045 COIS- Competing Interests: Dr. Mari served as a symposia speaker from Eli Lilly and Astra Zeneca. Also Dr. Bressan has received honoraria and/or consultations fees from Astra Zeneca, Janssen and Lundbeck; has received research funding from Janssen, Eli Lilly, Lundibeck, Novartis and Roche; and is a shareholder of Biomolecular Technology Ltda. Dr. Gadelha reports having received PhD fellowship from CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) and served as a speaker from Janssen-Cilag. The other authors have no conflicts of interest to disclose. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2014/02/06 06:00 MHDA- 2014/12/15 06:00 PMCR- 2014/02/03 CRDT- 2014/02/06 06:00 PHST- 2013/05/14 00:00 [received] PHST- 2014/01/02 00:00 [accepted] PHST- 2014/02/06 06:00 [entrez] PHST- 2014/02/06 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] PHST- 2014/02/03 00:00 [pmc-release] AID - PONE-D-13-19559 [pii] AID - 10.1371/journal.pone.0087686 [doi] PST - epublish SO - PLoS One. 2014 Feb 3;9(2):e87686. doi: 10.1371/journal.pone.0087686. eCollection 2014.