PMID- 29748862 OWN - NLM STAT- MEDLINE DCOM- 20181023 LR - 20221207 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 74 IP - 8 DP - 2018 Aug TI - Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients. PG - 1011-1020 LID - 10.1007/s00228-018-2463-z [doi] AB - PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. FAU - Wang, Peipei AU - Wang P AD - Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai, 201203, People's Republic of China. FAU - Zhang, Cuizhen AU - Zhang C AD - Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai, 201203, People's Republic of China. FAU - Lv, Qinyu AU - Lv Q AD - Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wanping Rd, Shanghai, 200030, People's Republic of China. FAU - Bao, Chenxi AU - Bao C AD - Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wanping Rd, Shanghai, 200030, People's Republic of China. FAU - Sun, Hong AU - Sun H AD - Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai, 201203, People's Republic of China. FAU - Ma, Guo AU - Ma G AD - Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai, 201203, People's Republic of China. FAU - Fang, Yiru AU - Fang Y AD - Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wanping Rd, Shanghai, 200030, People's Republic of China. FAU - Yi, Zhenghui AU - Yi Z AD - Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 Wanping Rd, Shanghai, 200030, People's Republic of China. yizhenghui1971@163.com. FAU - Cai, Weimin AU - Cai W AD - Department of Clinical Pharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai, 201203, People's Republic of China. weimincai@fudan.edu.cn. LA - eng GR - 2016YFC1307100/National Key R & D Program of China/ GR - 2016YFC1305904/National Key R & D Program of China/ GR - 2016YFC0906402/the National Basic Research Program of China/ GR - 81671326/the National Natural Science Foundation of China/ GR - 17411970000/Shanghai Science and Technology Commission Foundation/ PT - Clinical Trial PT - Journal Article DEP - 20180510 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0DHU5B8D6V (Citalopram) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Adolescent MH - Adult MH - Age Factors MH - Aged MH - Antidepressive Agents/pharmacology/therapeutic use MH - Asian People/*genetics MH - Brain-Derived Neurotrophic Factor/*genetics MH - China/ethnology MH - Citalopram/*pharmacology/*therapeutic use MH - DNA Methylation/*drug effects MH - Depression/*drug therapy/*genetics MH - Ethnicity/*genetics MH - Female MH - Genotype MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/genetics MH - Stress, Psychological MH - Treatment Outcome MH - Young Adult OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - DNA methylation OT - Escitalopram OT - Major depressive disorder OT - Polymorphism EDAT- 2018/05/12 06:00 MHDA- 2018/10/24 06:00 CRDT- 2018/05/12 06:00 PHST- 2017/12/25 00:00 [received] PHST- 2018/04/11 00:00 [accepted] PHST- 2018/05/12 06:00 [pubmed] PHST- 2018/10/24 06:00 [medline] PHST- 2018/05/12 06:00 [entrez] AID - 10.1007/s00228-018-2463-z [pii] AID - 10.1007/s00228-018-2463-z [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2018 Aug;74(8):1011-1020. doi: 10.1007/s00228-018-2463-z. Epub 2018 May 10.