Evaluation of neurotransmitter receptor gene expression identifies GABA receptor changes: A follow-up study in antipsychotic-naïve patients with first-episode psychosis

• Published in: Journal of psychiatric research Vol. 56; pp. 130 - 136
• Main Authors: Ota, Vanessa Kiyomi, Noto, Cristiano, Gadelha, Ary, Santoro, Marcos Leite, Ortiz, Bruno Bertolucci, Andrade, Elvis Henrique, Tasso, Brazilio Carvalho, Spindola, Leticia Maria Nery, Silva, Patricia Natalia, Abílio, Vanessa Costhek, Smith, Marília de Arruda Cardoso, Sato, João Ricardo, Brietzke, Elisa, Cordeiro, Quirino, Bressan, Rodrigo Affonseca, Belangero, Sintia Iole
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-09-2014; Elsevier
• Subjects: Adult and adolescent clinical studies; Antipsychotic Agents - therapeutic use; Antipsychotic drugs; Biological and medical sciences; Blood; Down-Regulation; Female; First time; Follow-Up Studies; GABA Rho-2; Gene expression; Gene Expression - drug effects; Genes; Humans; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychiatric Status Rating Scales; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychotic Disorders - blood; Psychotic Disorders - drug therapy; Receptors, GABA-A - blood; Receptors, GABA-A - genetics; Risperidone; Risperidone - therapeutic use; RNA, Messenger - blood; Schizophrenia; Treatment Outcome; Young Adult; serial analysis of gene expression; RNA; actin, beta; hypoxanthine phosphoribosyltransferase 1; SAGE; ABAT; COMT; cholinergic receptor, nicotinic, epsilon (muscle); ACTB; GABRR2; Ct; threshold cycle; TSPO; qPCR; PANSS; Risperidone; B2M; neuregulin 1; catechol-O-methyltransferase; CHRNB1; HKG; first-episode psychosis; TACR2; RPL13A; gamma-aminobutyric acid; NRG1; Gene expression; glutamic acid decarboxylase 67; GCHFR; translocator protein (18 kDa); GABA; HPRT1; GAPDH; PCR; ribonucleic acid; Schizophrenia; Positive and Negative Syndrome Scale; GTP cyclohydrolase 1; SCID; ribosomal protein L13a; tachykinin receptor 2; RELN; CHRNE; beta-2-microglobulin; GTP cyclohydrolase I feedback regulator; gamma-aminobutyric acid (GABA) receptor, rho 2; glyceraldehyde-3-phosphate dehydrogenase; polymerase chain reaction; GCH1; GABA Rho-2; quantitative polymerase chain reaction; GAD67; FEP; gamma-aminobutyric acid (GABA)receptor, rho 2; reelin; 4-Aminobutyrate Aminotransferase; Structured Clinical Interview for DSM-IV; cholinergic receptor, nicotinic, beta 1 (muscle); housekeeping genes; Human; Evaluation; Atypical antipsychotic; Neuroleptic; Psychotropic; Dopamine antagonist; Serotonin antagonist; Serotonine receptor; Genetic determinism; Psychosis; Gabaergic receptor; D2 Dopamine receptor; First episode; Follow up study; Neurotransmitter; Genetics; Benzisoxazole derivatives; Biological receptor
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2014.05.012

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.