Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients
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The neurotrophin brain-derived neurotrophic factor (BDNF) has been found to be associated with both the pathophysiology of depression and antidepressants response. Gene expression differences were partly mediated by SNP, which might be identified as a predictor of antidepressant response. In the present study, we attempt to identify whether DNA methylation, another factor known to affect gene transcription, might also predict antidepressant response.
A total of 85 depressed Chinese Han patients were followed-up 8 weeks after initiating escitalopram treatment. Treatment response was assessed by changes in the Hamilton Depression Rating Scale-17 (HAMD-17) score. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) were utilized as the assessment of previous life stress. The bisulfate sequencing was used to assess DNA methylation. Four single nucleotide polymorphisms (SNPs) in the BDNF gene were genotyped using PCR-RFLP or PCR sequencing.
We identified a DNA methylation predictor (P = 0.006–0.036) and a DNA methylation by LES interaction predictor (OR = 1.442 [1.057–1.968], P = 0.021) of general antidepressant treatment response. Lower mean BDNF DNA methylation was associated with impaired antidepressant response. Furthermore, the present data indicated that age, life stress, and SNPs genotype might be likely related to DNA methylation status. Average DNA methylation of BDNF at baseline was significantly lower than that at endpoint after 8 weeks of escitalopram treatment, which was based only on a subset of cases (n = 44).
Our results suggest that BDNF DNA hypomethylation and its interaction with lower LES score might result in impaired antidepressant treatment response. The pharmacoepigenetic study could eventually help in finding epigenetic biomarkers of antidepressant response.
KeywordsMajor depressive disorder Escitalopram Brain-derived neurotrophic factor Polymorphism DNA methylation
We gratefully acknowledge the data analysis support of Dr. Caifu Xue.
Weimin Cai, Zhenghui Yi, and Peipei Wang conceived and designed the study. Peipei Wang and Weimin Cai wrote the manuscript. Peipei Wang contributed to the data analysis. Peipei Wang, Cuizhen Zhang, Qinyu Lv, Yiru Fang, and Zhenghui Yi collected the samples. Peipei Wang, Hong Sun, Cuizhen Zhang, and Guo Ma contributed to the reagents, materials, and analysis tools. All the authors read and approved the final manuscript.
This work was supported by the National Key R&D Program of China (2016YFC1307100, 2016YFC1305904), the National Basic Research Program of China (Precision Psychiatry Program 2016YFC0906402), the National Natural Science Foundation of China (81671326), the CAS Key Laboratory of Mental Health (KLMH2018K02), the combination of traditional Chinese and Western medicine in Shanghai general hospital in 2017 (ZHYY-ZXYJHZX-2-201708), and the Shanghai Science and Technology Commission Foundation (17411970000).
Compliance with ethical standards
The study was approved by the ethics committees of Shanghai Mental Health Center (2012-26R) and performed according to the Declaration of Helsinki and the International Conference on Harmonization-Good Clinical Practice standards. All participating subjects received a description of the study and gave informed written consent.
The authors declare that they have no conflict of interest.
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