Dataset Information

A methylation study of long-term depression risk.

ABSTRACT: Recurrent and chronic major depressive disorder (MDD) accounts for a substantial part of the disease burden because this course is most prevalent and typically requires long-term treatment. We associated blood DNA methylation profiles from 581 MDD patients at baseline with MDD status 6 years later. A resampling approach showed a highly significant association between methylation profiles in blood at baseline and future disease status (P?=?2.0?×?10-16). Top MWAS results were enriched specific pathways, overlapped with genes found in GWAS of MDD disease status, autoimmune disease and inflammation, and co-localized with eQTLS and (genic enhancers of) of transcription sites in brain and blood. Many of these findings remained significant after correction for multiple testing. The major themes emerging were cellular responses to stress and signaling mechanisms linked to immune cell migration and inflammation. This suggests that an immune signature of treatment-resistant depression is already present at baseline. We also created a methylation risk score (MRS) to predict MDD status 6 years later. The AUC of our MRS was 0.724 and higher than risk scores created using a set of five putative MDD biomarkers, genome-wide SNP data, and 27 clinical, demographic and lifestyle variables. Although further studies are needed to examine the generalizability to different patient populations, these results suggest that methylation profiles in blood may present a promising avenue to support clinical decision making by providing empirical information about the likelihood MDD is chronic or will recur in the future.

SUBMITTER: Clark SL

PROVIDER: S-EPMC7061076 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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A methylation study of long-term depression risk.

Clark Shaunna L SL Hattab Mohammad W MW Chan Robin F RF Shabalin Andrey A AA Han Laura K M LKM Zhao Min M Smit Johannes H JH Jansen Rick R Milaneschi Yuri Y Xie Lin Ying LY van Grootheest Gerard G Penninx Brenda W J H BWJH Aberg Karolina A KA van den Oord Edwin J C G EJCG

Molecular psychiatry 20190909 6

Recurrent and chronic major depressive disorder (MDD) accounts for a substantial part of the disease burden because this course is most prevalent and typically requires long-term treatment. We associated blood DNA methylation profiles from 581 MDD patients at baseline with MDD status 6 years later. A resampling approach showed a highly significant association between methylation profiles in blood at baseline and future disease status (P = 2.0 × 10<sup>-16</sup>). Top MWAS results were enriched s ...[more]

PMID: 31501512

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Project description:IntroductionDepressive disorders are very common diseases entailing a great burden on affected people. However, comprehensive information on long-term disease course in patients with severe depression is lacking so far. The objectives of the DELTA study are to examine long-term outcomes and their predicting factors, to assess clinical response of antidepressant pharmacotherapy by applying therapeutic drug monitoring, to identify predictors of therapeutic non-response, to describe the long-term healthcare utilisation and to investigate the role of biomarkers in disease course.Methods and analysisA cohort study including all adult hospitalised cases (age range 18 to 75 years) of severe major depression who are admitted to the Bezirkskrankenhaus Augsburg is established. It is planned to include 300 patients. During the hospital stay, information is gathered through personal interview, self-administered questionnaires, cognitive tests and chart review. Furthermore, biomaterials are collected. After hospital discharge, patients are repeatedly re-examined over time (3, 6, 12, 24 and 36 months) to collect information about mortality, relapse, depression severity, health-related quality of life (HRQOL), perceived stigma, cognitive functions, diet, physical activity, treatment and healthcare utilisation. Follow-up blood samples are collected to determine therapeutic drug levels. The primary study aim is to investigate long-term therapeutic response, survival, relapse, HRQOL and cognitive functions. Survival time and time to relapse or re-hospitalisation will be analysed using Cox regression models. Changes of HRQOL, depressive symptoms and cognitive functions over time will be examined using generalised linear regression models for repeated measures or mixed models. Correlates of the disease course will be modelled using suitable generalised linear, mixed, estimating equation and growth curve models.Ethics and disseminationThe study protocol was approved by the Ethics Committee of the Ludwig-Maximilians-Universität München (date of approval: 23 October 2017, reference number: 17-625). Study results will be presented at scientific conferences and published in peer-reviewed scientific journals.

Project description:ImportanceBiomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent.ObjectiveTo examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders.Design, setting, and participantsThis population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023.ExposuresLipid, apolipoprotein, and carbohydrate biomarkers measured in blood.Main outcomes and measuresThe associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls.ResultsA total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants.Conclusions and relevanceIn this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

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Dataset Information

A methylation study of long-term depression risk.

Publications

A methylation study of long-term depression risk.

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