Epigenetic mechanisms such as DNA methylation are biochemical modifications of the DNA or its spatial structure regulating gene function and dynamically responding to environmental influences. This symposium aims at presenting some of the most recent advances in the field of epigenetics at the crossroads between genes and environment within the vulnerability-stress-model of mental disorders and at providing a platform to discuss its promises and pitfalls.
J. Martins will present a recent study suggesting an epigenetic embedding of early life stress by showing altered DNA methylation trajectories in a longitudinal cohort of children aged 3 to 5 years, who have been exposed to maltreatment. Given that genetic variation is a strong driver of epigenetic differences, another study investigating the effects of genotype, childhood adversity and their interaction on DNA methylation in five independent cohorts will be presented by D. Czamara. M. Schiele will review recent findings on DNA methylation in candidate genes with regard to categorical diagnoses of anxiety- and stress-related disorders such as panic disorder, specific phobia, social anxiety disorder and obsessive-compulsive disorder as well as regarding its possible role as a dynamic correlate of clinical response to psychotherapy. Along these lines, J. Frank will present recent findings from longitudinal genome-wide methylation studies in patients undergoing alcohol withdrawal, electroconvulsive therapy or therapeutic sleep deprivation suggesting epigenetic processes as possible mechanistic correlates of response to clinical interventions.
In sum, epigenetic research carries some promise to take the field closer to clinical application comprising resilience-increasing indicated preventive measures or in high-risk groups as well as more targeted, personalized and innovative treatment options for mental disorders.
16:00 Uhr
Effects of early life adversity on longitudinal DNA methylation trajectories
Jade Martins, München (Germany)
Details anzeigen
Autor:in:
Jade Martins, München (Germany)
Childhood maltreatment (CM) has been established as major risk factor for negative health outcomes at a later point in time. Epigenetic mechanisms, such as DNA methylation (DNAm), are considered to be the main route of embedding of environmental factors, including social environments.
We investigated the effects of CM on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study, a cohort of 173 children with (n=86) and without (n=87) maltreatment aged 3-5 years at baseline. DNAm measurements (using Infinium MethylationEPIC arrays), psychological and biological assessments were performed at five time points across 2,5 years (every 6 months).
We tested the effects of CM on DNAm over time in the 10% most variable (n=83,021) of all assessed CpGs and found no strong effects on single CpG level (differences in DNAm level < 2%). Expanding our analysis, we identified multiple differentially methylated regions over time. We further observed epigenetic signatures of prenatal exposures, based on epigenetic scores for tobacco and alcohol consumption during pregnancy. The maltreated group presented with significantly higher scores as compared to the control group (p(tobacco) = 0.03, p(alcohol) = 0.04). Finally, we performed weighted correlation network analysis which revealed a module of CpGs associated with DNAm alterations specific to maltreatment.
Our results suggest, that, while no strong maltreatment effect on single CpG level could be identified, CM presents with specific epigenetic signatures when combining DNAm of multiple CpGs.
16:10 Uhr
Combined effects of child adversity and genotype on DNA methylation
Darina Czamara, München (Germany)
Details anzeigen
Autor:in:
Darina Czamara, München (Germany)
Background:
Although several studies have proposed that the lasting effects of exposure to childhood adversity may in part be embedded via epigenetic mechanisms, evidence from epigenome-wide association studies (EWAs) is still limited and inconsistent. This is likely due to the fact that genetic variation is a strong driver of epigenetic variability, including DNA methylation (DNAm) and yet is often unaccounted for.
Methods:
We studied the contribution of CA, cis genotype (G), and their additive (G+CA) and interactive (G×CA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1,074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA which was assessed retrospectively using self-reports or verified through social services and registries.
Results:
For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G+CA or G×CA but almost never by CA alone. Across ages and tissues, 1,672 DNAm sites showed consistency of the best model in all five cohorts, with G×CA interactions explaining most variance in 80% of these consistent DNAm sites. The consistent G×CA sites mapped to genes enriched in brain specific transcripts and gene ontology terms related to development and synaptic function.
Conclusions:
Interaction of CA with genotypes in cis show the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.
16:20 Uhr
Patho- and therapyepigenetics of the anxiety-/obsessive-compulsive spectrum
Miriam A. Schiele, Freiburg im Breisgau (Germany)
Details anzeigen
Autor:in:
Miriam A. Schiele, Freiburg im Breisgau (Germany)
Epigenetic mechanisms such as DNA methylation are biochemical modifications of the DNA or its spatial structure. They regulate gene function, can be modified by environmental influences and are temporally dynamic. Altered DNA methylation patterns are not only implied in the mediation of environmental factors towards increasing – or decreasing – the risk for mental disorders, but have moreover been suggested as predictors and signatures of treatment response.
In this talk, recent findings on DNA methylation in select candidate genes will be reviewed with regard to categorical diagnoses of anxiety- and stress-related disorders such as panic disorder, specific phobia and obsessive-compulsive disorder (OCD). Also, the role of DNA methylation as a predictor or dynamic correlate of psychotherapeutic treatment response applying a ‘therapy-epigenetic’ approach in anxiety disorders and OCD will be discussed.
Epigenetic research carries great potential for clinical application and is hoped to in the future move the field towards more targeted, personalized and innovative treatment options in line with a ‘precision medicine’ approach.
16:30 Uhr
Modifications of epigenetic profiles after therapeutic interventions - some clinical examples
Josef Frank, Mannheim (Germany)
Details anzeigen
Autor:in:
Josef Frank, Mannheim (Germany)
Background and Aims: Depression and substance use disorders are serious - and often comorbid - disorders heavily impacting quality of life. The involvement of epigenetic processes in these disorders, as well as in treatment outcome has been suggested.
In our studies we aimed to identify genes and pathways involved in treatment-related processes, which hint to relevant mechanisms underlying changes happening in these contexts and could help understanding the disorder and improving the clinical outcome.
Methods: In several clinical settings (therapeutic alcohol withdrawal of severely dependent patients; therapeutic sleep deprivation and electroconvulsive therapy in patients with major depression) patients were assessed before and after treatment. Methylation levels were assessed genome-wide using Illumina Epic Chips. Methylation levels at both time points were compared with each other, as well as against those of healthy controls.
Results: During alcohol withdrawal extensive epigenome wide changes were observed. Analysis of differentially methylated regions and pathway based analyses revealed pronounced involvement of immune system related genes/pathways.
Only suggestive but no epigenome-wide significant associations of methylation profile changes could be observed wake therapy or ECT. Rather methylation levels seemed to be associated with response.
Discussion: Possible explanations will be proposed, why therapeutic withdrawal from ethanol was associated with far stronger methylation differences than those caused by wake therapy or ECT in depression. Furthermore, we will discuss potential pitfalls which have to be considered when performing methylation studies in psychiatric disorders and therapy .