title: Evaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: a follow-up study in antipsychotic-naïve patients with first-episode psychosis.
abstract: A study of the gene expression levels in the blood of individuals with schizophrenia in the beginning of the disease, such as first-episode psychosis (FEP), is useful to detect gene expression changes in this disorder in response to treatment. Although a large number of genetic studies on schizophrenia have been conducted, little is known about the effects of antipsychotic treatment on gene expression. The aim of the present study was to examine differences in the gene expression in the blood of antipsychotic-naïve FEP patients before and after risperidone treatment (N = 44) and also to verify the correlation with treatment response. In addition, we determined the correlations between differentially expressed genes and clinical variables. The expression of 40 neurotransmitter and neurodevelopment-associated genes was assessed using the RT2 Profiler PCR Array. The results indicated that the GABRR2 gene was downregulated after risperidone treatment, but no genes were associated with response to treatment and clinical variables after Bonferroni correction. GABRR2 downregulation after treatment can both suggest an effect of risperidone treatment or processes related to disease progression, either not necessarily associated with the improvement of symptoms. Despite this change was observed in blood, this decrease in GABRR2 mRNA levels might be an effect of changes in GABA concentrations or other systems interplay consequently to D2 blockage induced by risperidone, for example. Thus, it is important to consider that antipsychotics or the progression of psychotic disorders might interfere with gene expression.
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), Rua Botucatu, 740, Edifício Leitao da Cunha, 1° andar, CEP 04023-900, São Paulo, Brazil; LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil. Electronic address: vanessakaota@gmail.com.
authors.forename: Vanessa Kiyomi
authors.initials: VK
authors.lastname: Ota
authors.affiliation: LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil; Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. Electronic address: csnoto@gmail.com.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Noto
authors.affiliation: LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: aryararipe@yahoo.com.br.
authors.forename: Ary
authors.initials: A
authors.lastname: Gadelha
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), Rua Botucatu, 740, Edifício Leitao da Cunha, 1° andar, CEP 04023-900, São Paulo, Brazil; LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil. Electronic address: santorogen@gmail.com.
authors.forename: Marcos Leite
authors.initials: ML
authors.lastname: Santoro
authors.affiliation: Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: ortiz_bru@hotmail.com.
authors.forename: Bruno Bertolucci
authors.initials: BB
authors.lastname: Ortiz
authors.affiliation: Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: ehsa84@gmail.com.
authors.forename: Elvis Henrique
authors.initials: EH
authors.lastname: Andrade
authors.affiliation: Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. Electronic address: braztasso@ymail.com.
authors.forename: Brazilio Carvalho
authors.initials: BC
authors.lastname: Tasso
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), Rua Botucatu, 740, Edifício Leitao da Cunha, 1° andar, CEP 04023-900, São Paulo, Brazil; LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil. Electronic address: leticia.n.spindola@gmail.com.
authors.forename: Leticia Maria Nery
authors.initials: LM
authors.lastname: Spindola
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), Rua Botucatu, 740, Edifício Leitao da Cunha, 1° andar, CEP 04023-900, São Paulo, Brazil; LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, 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, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil; Department of Pharmacology, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: vanabilio@gmail.com.
authors.forename: Vanessa Costhek
authors.initials: VC
authors.lastname: Abílio
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), Rua Botucatu, 740, Edifício Leitao da Cunha, 1° andar, CEP 04023-900, São Paulo, Brazil. Electronic address: macsmith.morf@epm.br.
authors.forename: Marília de Arruda Cardoso
authors.initials: Mde A
authors.lastname: Smith
authors.affiliation: LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil. Electronic address: joao.sato@ufabc.edu.br.
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Sato
authors.affiliation: LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: elisabrietzke@hotmail.com.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
authors.affiliation: Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil; Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. Electronic address: qcordeiro@yahoo.com.
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.affiliation: LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: rodrigoabressan@gmail.com.
authors.forename: Rodrigo Affonseca
authors.initials: RA
authors.lastname: Bressan
authors.affiliation: Genetics Division, Department of Morphology and Genetics, Universidade Federal de Sao Paulo (UNIFESP), Rua Botucatu, 740, Edifício Leitao da Cunha, 1° andar, CEP 04023-900, São Paulo, Brazil; LiNC - Interdisciplinary Laboratory of Clinical Neurosciences, Universidade Federal de Sao Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3° andar fundos, CEP 05039-032, São Paulo, Brazil; Department of Psychiatry, Universidade Federal de Sao Paulo (UNIFESP), São Paulo, Brazil. Electronic address: sinbelangero@gmail.com.
authors.forename: Sintia Iole
authors.initials: SI
authors.lastname: Belangero
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood* / Q000188:drug therapy*; D012333:RNA, Messenger / Q000097:blood; D011963:Receptors, GABA-A / Q000097:blood / Q000235:genetics*; D018967:Risperidone / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C106350:GABRR2 protein, human; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D018967:Risperidone
keywords: GABA Rho-2; Gene expression; Risperidone; Schizophrenia