What do DNA methylation studies tell us about depression? A systematic review
Open accessAbstract
There has been a limited number of systematic reviews conducted to summarize the overview of the relationship between DNA methylation and depression, and to critically appraise the roles of major study characteristics in the accuracy of study findings. This systematic review aims to critically appraise the impact of study characteristics on the association between DNA methylation and depression, and summarize the overview of this association. Electronic databases and gray literatures until December 2017 were searched for English-language studies with standard diagnostic criteria of depression. A total of 67 studies were included in this review along with a summary of their study characteristics. We grouped the findings into etiological and treatment studies. Majority of these selected studies were recently published and from developed countries. Whole blood samples were the most studied common tissues. Bisulfite conversion, along with pyrosequencing, was widely used to test the DNA methylation level across all the studies. High heterogeneity existed among the studies in terms of experimental and statistical methodologies and study designs. As recommended by the Cochrane guideline, a systematic review without meta-analysis should be undertaken. This review has, in general, found that DNA methylation modifications were associated with depression. Subgroup analyses showed that most studies found BDNF and SLC6A4 hypermethylations to be associated with MDD or depression in general. In contrast, studies on NR3C1 , OXTR , and other genes, which were tested by only few studies, reported mixed findings. More longitudinal studies using standardized experimental and laboratory methodologies are needed in future studies to enable more systematical comparisons and quantitative synthesis.
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There is very limited evidence for altered DNA methylation in peripheral blood in patients with MDD.
“Overall, there is very limited evidence for altered DNAm in peripheral blood in patients with MDD.”
From Epigenetics and depression (2019) · cites this paper as [13]
The Results (Etiological studies: candidate-gene; page unavailable) say most studies associated BDNF and SLC6A4 hypermethylation with MDD or depression. The review also lists significant findings from whole-blood and peripheral-blood studies, so its account is contrary to the claim that evidence of altered methylation in peripheral blood is very limited, although it notes mixed findings for other genes. (LLM, conf=0.82)
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Experimental — accuracy not yet measuredA systematic review of 67 publications, 61 in peripheral tissue, concluded there was evidence for DNA methylation differences between cases and controls at selected loci.
“A recent systematic review of 67 publications, 13 61 of which were done in peripheral tissue, mainly blood cells, concluded there was evidence for DNAm differences between cases and controls at selected loci.”
From Epigenetics and depression (2019) · cites this paper as [13]
The Results report 67 included articles and case–control differences at specific methylation sites; the Discussion says whole blood was the most common tissue. The passages support the review’s general conclusion, but they do not establish the precise count of 61 studies using peripheral tissue. (LLM, conf=0.82)
Experimental — accuracy not yet measuredGenome-wide methylation studies found DNA methylation significantly associated with MDD at some loci, but no consistent changes in direction or position have been identified.
“Genome-wide methylation approaches were also included, and although all studies found that DNAm was significantly associated with MDD at some loci, no consistent changes, either for direction or position, have been identified.”
From Epigenetics and depression (2019) · cites this paper as [13]
The findings of hypermethylation in BDNF and SLC6A4 are not consistent across all studies.
“However, even these findings are not consistent across all studies”
From Epigenetics and depression (2019) · cites this paper as [13]
Candidate gene studies most consistently found that MDD patients had hypermethylation in the BDNF and SLC6A4 loci.
“Most consistently, candidate gene studies found that patients with MDD had hypermethylation in the loci encoding brain derived neurotrophic factor ( BDNF ), and SLC6A4 , the serotonin transporter gene.”
From Epigenetics and depression (2019) · cites this paper as [13]
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References 78 · Cited by 125
- Authors
- Li, M., D’Arcy, C., Li, X., Zhang, T., Joober, R., & Meng, X.
- Affiliations
- University of Saskatchewan (CA)
- Mitacs (CA)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Meng, Xiangfei
- Venue
- Translational Psychiatry
- Published
- 2019-02-04
- Volume
- 9
- Issue
- 1
- Pages
- 68-68
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6362194
- OpenAlex
- W2922125887
- Cited by
- 125
- References
- 78
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 16 · 2023: 18 · 2022: 22 · 2021: 25 · 2020: 23 · 2019: 4
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (publishedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research (PJT-148845)
- Fonds de Recherche du Québec - Santé (Researcher scholarship)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- DNA methylation, depression, major depressive disorder, brain-derived neurotrophic factor, serotonin transporter, NR3C1, oxytocin receptor, epigenetics, methylation biomarkers, study characteristics, heterogeneity
- MeSH terms
- Depression, Depressive Disorder, Humans, DNA Methylation
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