Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients

Wang, Peipei; Zhang, Cuizhen; Lv, Qing; Bao, Chenxi; Sun, Hong; Ma, Guoyi; Fang, Yiru; Yi, Zhenghui; Cai, Weimin

doi:10.1007/s00228-018-2463-z

Cited by 45 publications

(39 citation statements)

References 44 publications

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“…Antidepressants' effects on histone modifications may be more important in increasing BDNF expression than DNA methylation of the promoter. BDNF promoter hypomethylation predicted poor response to antidepressant treatment [52,55], but corresponded with greater improvement in suicidality in a separate study [54]. However, increased BDNF promoter methylation after antidepressant treatment correlated with depression remission [52,57].…”

Section: Discussionmentioning

confidence: 88%

“…Eight weeks of escitalopram was associated with significantly increased average BDNF promoter and any amplicon methylation compared to pre-treatment in a subset of forty-four MDD subjects. In remitters, BDNF promoter methylation was significantly increased after eight weeks of escitalopram treatment, while in the non-remitter group, there was no significant increase in methylation post-treatment [52].…”

Section: Bdnf (Brain-derived Neurotrophic Factor)mentioning

confidence: 79%

“…The neurotrophic hypothesis of depression posits that depression should be associated with decreased BDNF expression [89], potentially driven by BDNF hypermethylation. However, four studies reported antidepressant use associated with hypermethylation of the BDNF promoter [49][50][51][52]. D'Addario et al's 2012 study explored bipolar subtypes and found higher methylation in BD2, a subtype which may present with more depressive episodes than BD1, although this was not explicitly explored in the paper [49].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that early increases in serum and plasma BDNF levels within the first seven to fourteen days of starting an antidepressant medication may predict improvement in MDD symptoms after six weeks of treatment [56,90]. Counterintuitively, a pre-treatment hypomethylated BDNF promoter has been associated with poor antidepressant response [52,55]. Perhaps antidepressants increase BDNF expression through a mechanism other than decreasing methylation of the BDNF promoter, such as by decreasing H3K27 methylation in BDNF exon IV.…”

Section: Discussionmentioning

confidence: 99%

“…Additional evidence that antidepressants increase BDNF promoter methylation in MDD came from an eight week trial of the SSRI, escitalopram, in eighty-five MDD patients [52]. Mean methylation across the entire BDNF gene was not associated with antidepressant response (p = 0.052), however, remitters had significantly increased BDNF promoter methylation at four specific amplicons of the BDNF promoter: 1, 3, 4, and 5.…”

Section: Bdnf (Brain-derived Neurotrophic Factor)mentioning

confidence: 99%

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The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

Webb

Phillips

et al. 2020

IJMS

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Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD’s etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals’ unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.

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Section: Discussionmentioning

confidence: 88%

Section: Bdnf (Brain-derived Neurotrophic Factor)mentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Bdnf (Brain-derived Neurotrophic Factor)mentioning

confidence: 99%

See 3 more Smart Citations

The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

Webb

Phillips

et al. 2020

IJMS

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Leveraging DNA methylation to predict treatment response in major depressive disorder: A critical review

Dahrendorff,

Currier,

Uddin

2024

American J of Med Genetics Pt B

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Major depressive disorder (MDD) is a debilitating and prevalent mental disorder with a high disease burden. Despite a wide array of different treatment options, many patients do not respond to initial treatment attempts. Selection of the most appropriate treatment remains a significant clinical challenge in psychiatry, highlighting the need for the development of biomarkers with predictive utility. Recently, the epigenetic modification DNA methylation (DNAm) has emerged to be of great interest as a potential predictor of MDD treatment outcomes. Here, we review efforts to date that seek to identify DNAm signatures associated with treatment response in individuals with MDD. Searches were conducted in the databases PubMed, Scopus, and Web of Science with the concepts and keywords MDD, DNAm, antidepressants, psychotherapy, cognitive behavior therapy, electroconvulsive therapy, transcranial magnetic stimulation, and brain stimulation therapies. We identified 32 studies implicating DNAm patterns associated with MDD treatment outcomes. The majority of studies (N = 25) are focused on selected target genes exploring treatment outcomes in pharmacological treatments (N = 22) with a few studies assessing treatment response to electroconvulsive therapy (N = 3). Additionally, there are few genome‐scale efforts (N = 7) to characterize DNAm patterns associated with treatment outcomes. There is a relative dearth of studies investigating DNAm patterns in relation to psychotherapy, electroconvulsive therapy, or transcranial magnetic stimulation; importantly, most existing studies have limited sample sizes. Given the heterogeneity in both methods and results of studies to date, there is a need for additional studies before existing findings can inform clinical decisions.

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The role of BDNF exon I region methylation in the treatment of depression with sertraline and its clinical diagnostic value

Xing

Sun

et al. 2021

Clinical Laboratory Analysis

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Depression is one of the 10 most common diseases worldwide, and it is estimated that it will become the second most common disease by 2030. 1,2 Depressive patients are mainly characterized by depression, a decline in interest and fatigue, accompanied by varying degrees of impaired social function. 1,2 Thus far, no specific genetic, biological, biochemical or neuropathological changes have been identified as objective biological indicators of depression. 3 At present, treatment of depression is mainly based on the empirical use of

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Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients

Abstract: 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.

Cited by 45 publications

References 44 publications

The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

Leveraging DNA methylation to predict treatment response in major depressive disorder: A critical review

The role of BDNF exon I region methylation in the treatment of depression with sertraline and its clinical diagnostic value

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