Article

The epigenetic code in depression: implications for treatment.

Department of Psychiatry, Psychosomatic Medicine & Psychotherapy, Goethe University Frankfurt, Frankfurt, Germany.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 6.85). 12/2011; 91(2):310-4. DOI: 10.1038/clpt.2011.282
Source: PubMed

ABSTRACT Major depressive disorder (MDD) is a common and disabling disorder that carries both a substantial personal burden as well as a social one. A better understanding of the epigenetic mechanisms in depression might provide a new framework for individually tailored pharmacologic treatment options. In this review we highlight current knowledge about the role of epigenetic mechanisms in the pathogenesis of depression and treatment implications.

0 Bookmarks
 · 
66 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: During the last decade and a half, there has been an explosion of data regarding epigenetic changes in schizophrenia. Most initial studies have suggested that schizophrenia is characterized by an overly restrictive chromatin state based on increases in transcription silencing histone modifications and DNA methylation at schizophrenia candidate gene promoters and increases in the expression of enzymes that catalyze their formation. However, recent studies indicate that the pathology is more complex. This complexity may greatly impact pharmacological approaches directed at targeting epigenetic abnormalities in schizophrenia. The current review explores epigenetic studies of schizophrenia and what this can tell us about the underlying pathophysiology. We hypothesize based on recent studies that it is also plausible that drugs that further restrict chromatin may be efficacious.
    International Review of Neurobiology 01/2014; 115:155-201. · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Child maltreatment is associated with an increased risk of psychiatric disorders, and a range of health problems later in life. Research suggests that adverse events early in life can lead to changes in gene expression through epigenetic mechanisms that alter stress reactivity, brain function, and behaviour. Although epigenetic changes are often long lasting, they can be reversed with pharmacological and environmental manipulations. The complexity of the epigenome is not fully understood. The aim of this Review is to assess emerging data for the role of epigenetic mechanisms in stress-related psychiatric disorders with a focus on future research. We describe the epigenetic processes, key findings in this specialty, clinical implications of research, and methodological issues. Studies are needed to investigate new epigenetic processes other than methylation and assess the efficacy of interventions to reverse epigenetic processes associated with the effects of early life adversity.
    The Lancet Psychiatry 11/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The monoamine oxidase A (MAO-A) gene has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of major depressive disorder. In the present analysis, for the first time a pharmacoepigenetic approach was applied investigating the influence of DNA methylation patterns in the MAO-A regulatory and exon1/intron1 region on antidepressant treatment response. 94 patients of Caucasian descent with major depressive disorder (f = 61; DSM-IV) were analyzed for DNA methylation status at 43 MAO-A CpG sites via direct sequencing of sodium bisulfite treated DNA extracted from blood cells. Patients were also genotyped for the functional MAO-A VNTR. Clinical response to antidepressant treatment with escitalopram was assessed by intra-individual changes of HAM-D-21 scores after 6 weeks of treatment. Apart from two CpG sites, male subjects showed no or only very minor methylation. In female patients, lower methylation at two individual CpG sites in the MAO-A promoter region was nominally associated with impaired response to antidepressant treatment after 6 weeks (GRCh37/hg19: CpG 43.514.063, p = 0.04; CpG 43.514.684, p = 0.009), not, however, withstanding correction for multiple testing. MAO-A VNTR genotypes did not influence MAO-A methylation status. The present pilot data do not suggest a major influence of MAO-A DNA methylation on antidepressant treatment response. However, the presently observed trend towards CpG-specific MAO-A gene hypomethylation-possibly via increased gene expression and consecutively decreased serotonin and/or norepinephrine availability-to potentially drive impaired antidepressant treatment response in female patients might be worthwhile to be followed up in larger pharmacoepigenetic studies.
    Journal of Neural Transmission 05/2014; · 2.87 Impact Factor