DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder

So far, genetic studies of treatment response in schizophrenia, bipolar disorder, and major depression have returned results with limited clinical utility. A gene × environment interplay has been proposed as a factor influencing not only pathophysiology but also the treatment response. Therefore, epigenetics has emerged as a major field of research to study the treatment of these three disorders. Among the epigenetic marks that can modify gene expression, DNA methylation is the best studied. We performed a systematic search (PubMed) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines for preclinical and clinical studies focused on genome-wide and gene-specific DNA methylation in the context of schizophrenia, bipolar disorders, and major depressive disorder. Out of the 112 studies initially identified, we selected 31 studies among them, with an emphasis on responses to the gold standard treatments in each disorder. Modulations of DNA methylation levels at specific CpG sites have been documented for all classes of treatments (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the models and methodologies used complicate the interpretation of results. Although few studies in each disorder have assessed the potential of DNA methylation as biomarkers of treatment response, data support this hypothesis for antipsychotics, mood stabilizers and antidepressants.

Download Full-text

Polygenic scores for major depressive disorder and depressive symptoms predict response to lithium in patients with bipolar disorder

10.1101/449363 ◽

2018 ◽

Cited By ~ 1

Author(s):

Azmeraw T. Amare ◽

Klaus Oliver Schubert ◽

Liping Hou ◽

Scott R. Clark ◽

Sergi Papiol ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Symptoms ◽

Depressive Disorder ◽

Treatment Response ◽

Lithium Treatment ◽

Mapk Signaling ◽

Genome Wide Association Studies ◽

Major Depressive ◽

Polygenic Scores

AbstractBackgroundLithium is a first-line medication for bipolar disorder (BD), but only ~30% of patients respond optimally to the drug. Since genetic factors are known to mediate lithium treatment response, we hypothesized whether polygenic susceptibility to the spectrum of depression traits is associated with treatment outcomes in patients with BD. In addition, we explored the potential molecular underpinnings of this relationship.MethodsWeighted polygenic scores (PGSs) were computed for major depressive disorder (MDD) and depressive symptoms (DS) in BD patients from the Consortium on Lithium Genetics (ConLi+Gen; n=2,586) who received lithium treatment. Lithium treatment outcome was assessed using the ALDA scale. Summary statistics from genome-wide association studies (GWAS) in MDD (130,664 cases and 330,470 controls) and DS (n=161,460) were used for PGS weighting. Associations between PGSs of depression traits and lithium treatment response were assessed by binary logistic regression. We also performed a cross-trait meta-GWAS, followed by Ingenuity® Pathway Analysis.OutcomesBD patients with a low polygenic load for depressive traits were more likely to respond well to lithium, compared to patients with high polygenic load (MDD: OR =1.64 [95%CI: 1.26-2.15], lowest vs highest PGS quartiles; DS: OR=1.53 [95%CI: 1.18-2.00]). Associations were significant for type 1, but not type 2 BD. Cross-trait GWAS and functional characterization implicated voltage-gated potassium channels, insulin-related pathways, mitogen-activated protein-kinase (MAPK) signaling, and miRNA expression.InterpretationGenetic loading to depression traits in BD patients lower their odds of responding optimally to lithium. Our findings support the emerging concept of a lithium-responsive biotype in BD.FundingSee attached details

Download Full-text

Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Frontiers in Neuroscience ◽

10.3389/fnins.2021.674273 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jiaqi Zhou ◽

Miao Li ◽

Xueying Wang ◽

Yuwen He ◽

Yan Xia ◽

...

Keyword(s):

Dna Methylation ◽

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Clinical Improvement ◽

Drug Response ◽

Epigenetic Modification ◽

Antidepressant Treatment ◽

Future Research ◽

Major Depressive

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.

Download Full-text

Comparative Analysis of Spouse’s Burden and Quality of Life in Major Depressive Disorder and Bipolar I Disorder

Current Psychiatry Research and Reviews ◽

10.2174/1874464812666190819151039 ◽

2019 ◽

Vol 15 (3) ◽

pp. 193-198

Author(s):

Nayereh Maleki ◽

Effat Sadeghian ◽

Farshid Shamsaei ◽

Lily Tapak ◽

Ali Ghaleiha

Keyword(s):

Quality Of Life ◽

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Negative Impact ◽

Bipolar Disorders ◽

Coping Skill ◽

Major Depressive ◽

Cross Sectional

Background: Spouses of patients with bipolar disorder may experience a different quality of life and burden than seen with major depressive disorder. Objective: This study was conducted to comparatively analyse spouse’s burden and quality of life in major depressive and bipolar disorders. Methods: This cross-sectional study was conducted on 220 spouses of patients with major depressive and bipolar disorders in the city of Hamadan in Iran, in 2018. Data collection tools included Zarit Burden and QOL-BREF questionnaires. Data were analyzed by a t-test using SPSS -16. Results: The findings showed that 11.8% of spouses of patients with depression and 85.5% of spouses of patients with bipolar disorder experienced severe burden (P < 0.001). The quality of life of spouses of patients with bipolar disorder was lower than with depressive disorder (P < 0.05). In both the groups, a negative correlation was found between burden and QOL. Conclusion: The spouses of patients with bipolar disorder experience more burden and lower quality of life than depression. In both the groups, burden has a negative impact on the quality of life. Professional help and supportive intervention can be provided to the spouses of patients with major depressive and bipolar I disorders to reduce their burden, strengthen their coping skill and thus improve their QOL.

Download Full-text