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- Title
Methylation at a transcription factor-binding site on the 5-HT1A receptor gene correlates with negative symptom treatment response in first episode schizophrenia.
- Authors
Hao Tang; Dalton, Caroline F.; Srisawat, Umarat; Zhi Jun Zhang; Reynolds, Gavin P.
- Abstract
Individual variability and inadequate response of negative symptoms are major limitations of antipsychotic treat-ment in schizophrenia. A functional polymorphism, rs6295, in the 5-HTlA-receptor gene (HTR1A) contributes to this variability in negative symptom response. The DNA sequence containing rs6295 is rich in cytosine methyla-tion (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 methyla-tion 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 antipsy-chotic 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.
- Subjects
METHYLATION; TRANSCRIPTION factors; BINDING sites; SYMPTOMS; SCHIZOPHRENIA; ANTIPSYCHOTIC agents; PHARMACOGENOMICS
- Publication
International Journal of Neuropsychopharmacology, 2014, Vol 17, Issue 4, p645
- ISSN
1461-1457
- Publication type
Article
- DOI
10.1017/S1461145713001442