title: Methylation at a transcription factor-binding site on the 5-HT1A receptor gene correlates with negative symptom treatment response in first episode schizophrenia.
abstract: Individual variability and inadequate response of negative symptoms are major limitations of antipsychotic treatment in schizophrenia. A functional polymorphism, rs6295, in the 5-HT1A-receptor gene (HTR1A) contributes to this variability in negative symptom response. The DNA sequence containing rs6295 is rich in cytosine methylation (CpG) sites; CpG methylation is an epigenetic factor that, like rs6295, can modify transcriptional control. To investigate whether DNA methylation influences response to antipsychotic treatment, we determined methylation at CpG sites close to rs6295 in DNA from 82 Chinese subjects with a first psychotic episode. Methylation of one CpG site within a recognition sequence for HES transcriptional repressors was found to correlate with changes in total PANSS score (p = 0.006) and negative factor sub-score (p < 0.001) following 10 wk initial antipsychotic treatment, as well as with baseline negative factor score (p = 0.019); the effect on symptom change remained after correction for this baseline score. An effect of rs6295 on negative symptom response was not seen in this sample, which may not have provided sufficient power for the pharmacogenetic association. These preliminary results indicate that epigenetic modification of transcriptional regulation by specific cytosine methylation may modulate HTR1A expression, resulting in effects on emotional dysfunction and negative symptom response to antipsychotic treatment.
authors: Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
authors: Hao
authors: H
authors: Tang
authors: Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
authors: Caroline F
authors: CF
authors: Dalton
authors: Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
authors: Umarat
authors: U
authors: Srisawat
authors: Department of Neurology, ZhongDa Hospital and Institute of Neuropsychiatry, Southeast University, Nanjing, People's Republic of China.
authors: Zhi Jun
authors: ZJ
authors: Zhang
authors: Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
authors: Gavin P
authors: GP
authors: Reynolds
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D002681:China; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D014157:Transcription Factors; D044282:Receptor, Serotonin, 5-HT1A