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神经递质受体基因表达评估可识别γ-氨基丁酸(GABA)受体变化:首发精神病未服用抗精神病药物患者的随访研究

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

作者信息

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

机构信息

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.

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.

出版信息

J Psychiatr Res. 2014 Sep;56:130-6. doi: 10.1016/j.jpsychires.2014.05.012. Epub 2014 Jun 4.

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.

摘要

对精神分裂症患者(如首发精神病,FEP)疾病初期血液中的基因表达水平进行研究,有助于检测该疾病在治疗过程中的基因表达变化。尽管已经开展了大量关于精神分裂症的遗传学研究,但对于抗精神病药物治疗对基因表达的影响却知之甚少。本研究的目的是检查未使用过抗精神病药物的FEP患者在利培酮治疗前后血液中的基因表达差异(N = 44),并验证其与治疗反应的相关性。此外,我们还确定了差异表达基因与临床变量之间的相关性。使用RT2 Profiler PCR Array评估了40种神经递质和神经发育相关基因的表达。结果表明,利培酮治疗后GABRR2基因表达下调,但经Bonferroni校正后,没有基因与治疗反应和临床变量相关。治疗后GABRR2基因表达下调既可能提示利培酮治疗的效果,也可能提示与疾病进展相关的过程,不一定与症状改善相关。尽管在血液中观察到了这种变化,但GABRR2 mRNA水平的降低可能是例如利培酮诱导的D2阻断导致GABA浓度变化或其他系统相互作用的结果。因此,重要的是要考虑到抗精神病药物或精神障碍的进展可能会干扰基因表达。

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