title: Changes in gene expression and methylation in the blood of patients with first-episode psychosis.
abstract: Schizophrenia is a severe mental health disorder with high heritability. The investigation of individuals during their first-episode psychosis (FEP), before the progression of psychotic disorders and especially before treatment with antipsychotic medications, is particularly helpful for understanding this complex disease and for the identification of potential biomarkers. In this study, we compared the expression of genes that are involved in neurotransmission and neurodevelopment of antipsychotic-naive FEP in the peripheral blood of patients (n=51) and healthy controls (n=51). In addition, we investigated the differentially expressed genes with respect to a) DNA methylation, b) the correlation between gene expression and clinical variables (PANSS), and c) gene expression changes after risperidone treatment. Expression levels of 11 genes were quantified with SYBR Green. For methylation analysis, bisulfite sequencing was performed. A significant decrease in GCH1 mRNA levels was observed in FEP patients relative to controls. Also, when we compare the FEP patients after risperidone treatment with controls, this difference remains significant, and no significant differences were observed in GCH1 mRNA levels when comparing patients before and after risperidone treatment. Additionally, although the differences were non-significant after Bonferroni correction, the expression of GCH1 seemed to be correlated with PANSS scores, and the GCH1 promoter region was more methylated in FEP than in controls, thus corroborating the results obtained at the mRNA level. Few studies have been conducted on GCH1, and future studies are needed to clarify its potential role in the progression of schizophrenia.
authors.affiliation: Genetics Division of Department of Morphology and Genetics of Universidade Federal de Sao Paulo (UNIFESP), Brazil; LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil. Electronic address: vanessakaota@gmail.com.
authors.forename: Vanessa Kiyomi
authors.initials: VK
authors.lastname: Ota
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil; Department of Psychiatry of UNIFESP, Brazil; Department of Psychiatry of Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Brazil. Electronic address: csnoto@gmail.com.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Noto
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil; Department of Psychiatry of UNIFESP, Brazil. Electronic address: aryararipe@yahoo.com.br.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Genetics Division of Department of Morphology and Genetics of Universidade Federal de Sao Paulo (UNIFESP), Brazil; LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil. Electronic address: santorogen@gmail.com.
authors.forename: Marcos Leite
authors.initials: ML
authors.lastname: Santoro
authors.affiliation: Genetics Division of Department of Morphology and Genetics of Universidade Federal de Sao Paulo (UNIFESP), Brazil; LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil. Electronic address: leticia.n.spindola@gmail.com.
authors.forename: Leticia Maria
authors.initials: LM
authors.lastname: Spindola
authors.affiliation: Department of Psychiatry of UNIFESP, Brazil; Department of Psychiatry of Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Brazil. Electronic address: esgouvea@yahoo.com.
authors.forename: Eduardo Sauerbronn
authors.initials: ES
authors.lastname: Gouvea
authors.affiliation: Department of Biophysics of UNIFESP, Brazil. Electronic address: robertasessa@gmail.com.
authors.forename: Roberta Sessa
authors.initials: RS
authors.lastname: Stilhano
authors.affiliation: Department of Psychiatry of UNIFESP, Brazil. Electronic address: ortiz_bru@hotmail.com.
authors.forename: Bruno Bertolucci
authors.initials: BB
authors.lastname: Ortiz
authors.affiliation: Genetics Division of Department of Morphology and Genetics of Universidade Federal de Sao Paulo (UNIFESP), Brazil; LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil; Department of Psychiatry of UNIFESP, Brazil. Electronic address: patriciaoliveira.unifesp@gmail.com.
authors.forename: Patricia Natalia
authors.initials: PN
authors.lastname: Silva
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil; Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Brazil. Electronic address: joao.sato@ufabc.edu.br.
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Sato
authors.affiliation: Department of Biophysics of UNIFESP, Brazil. Electronic address: universo.han@gmail.com.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Han
authors.affiliation: Department of Psychiatry of UNIFESP, Brazil; Department of Psychiatry of Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Brazil. Electronic address: qcordeiro@yahoo.com.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.affiliation: LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil; Department of Psychiatry of UNIFESP, Brazil. Electronic address: rodrigoabressan@gmail.com.
authors.forename: Rodrigo Affonseca
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Genetics Division of Department of Morphology and Genetics of Universidade Federal de Sao Paulo (UNIFESP), Brazil; LiNC-Interdisciplinary Laboratory of Clinical Neurosciences of UNIFESP, Brazil; Department of Psychiatry of UNIFESP, Brazil. Electronic address: sinbelangero@gmail.com.
authors.forename: Sintia Iole
authors.initials: SI
authors.lastname: Belangero
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood*; D012333:RNA, Messenger / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000235:genetics; D018967:Risperidone / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D012333:RNA, Messenger; D018041:Receptors, Neurokinin-2; D006136:GTP Cyclohydrolase; D018967:Risperidone
keywords: BH4; GTP cyclohydrolase I; biopterin; gene expression; schizophrenia