Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial
Abstract Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are ne...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-07-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02032-7 |
| _version_ | 1811323705815465984 |
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| author | J. Engelmann L. Zillich J. Frank S. Wagner M. Cetin D. P. Herzog M. B. Müller A. Tadic J. C. Foo L. Sirignano D. F. Braus N. Dahmen S. Sordon M. Riemenschneider C. Spaniol G. Gasparoni M. Rietschel S. H. Witt K. Lieb F. Streit |
| author_facet | J. Engelmann L. Zillich J. Frank S. Wagner M. Cetin D. P. Herzog M. B. Müller A. Tadic J. C. Foo L. Sirignano D. F. Braus N. Dahmen S. Sordon M. Riemenschneider C. Spaniol G. Gasparoni M. Rietschel S. H. Witt K. Lieb F. Streit |
| author_sort | J. Engelmann |
| collection | DOAJ |
| description | Abstract Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment. |
| first_indexed | 2024-04-13T14:00:08Z |
| format | Article |
| id | doaj.art-9bc647eff8914bc592fd313c95b6e2e6 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-13T14:00:08Z |
| publishDate | 2022-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-9bc647eff8914bc592fd313c95b6e2e62022-12-22T02:44:04ZengNature Publishing GroupTranslational Psychiatry2158-31882022-07-011211910.1038/s41398-022-02032-7Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trialJ. Engelmann0L. Zillich1J. Frank2S. Wagner3M. Cetin4D. P. Herzog5M. B. Müller6A. Tadic7J. C. Foo8L. Sirignano9D. F. Braus10N. Dahmen11S. Sordon12M. Riemenschneider13C. Spaniol14G. Gasparoni15M. Rietschel16S. H. Witt17K. Lieb18F. Streit19Department of Psychiatry and Psychotherapy, University Medical CenterDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Psychiatry and Psychotherapy, University Medical CenterDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Psychiatry and Psychotherapy, University Medical CenterDepartment of Psychiatry and Psychotherapy, University Medical CenterDepartment of Psychiatry and Psychotherapy, University Medical CenterDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Psychiatry and Psychotherapy, Vitos RheingauDepartment of Psychiatry, Psychosomatics and Psychotherapy, Burghof-KlinikDepartment of Psychiatry and Psychotherapy, Saarland University Hospital (UKS)Department of Psychiatry and Psychotherapy, Saarland University Hospital (UKS)Department of Psychiatry and Psychotherapy, Saarland University Hospital (UKS)Department of Genetics, Saarland UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityDepartment of Psychiatry and Psychotherapy, University Medical CenterDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityAbstract Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment.https://doi.org/10.1038/s41398-022-02032-7 |
| spellingShingle | J. Engelmann L. Zillich J. Frank S. Wagner M. Cetin D. P. Herzog M. B. Müller A. Tadic J. C. Foo L. Sirignano D. F. Braus N. Dahmen S. Sordon M. Riemenschneider C. Spaniol G. Gasparoni M. Rietschel S. H. Witt K. Lieb F. Streit Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial Translational Psychiatry |
| title | Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial |
| title_full | Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial |
| title_fullStr | Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial |
| title_full_unstemmed | Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial |
| title_short | Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial |
| title_sort | epigenetic signatures in antidepressant treatment response a methylome wide association study in the emc trial |
| url | https://doi.org/10.1038/s41398-022-02032-7 |
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