Epigenetics in Psychiatry brings together a collection of researchers in the field of neuroepigenetics to provide insight into research on the role of epigenetics in a range of psychiatric disorders, including schizophrenia, major depressive disorder, bipolar disorder and suicide. Not content with covering only these topics it also provides information on the techniques and animal models used to study these areas, as well as chapters on epigenetic therapy for the treatment of psychiatric disorders.
In this book review, our recent raffle winner Dr. Efterpi Kostareli at the German Cancer Research Center (DKFZ), in Heidelberg, Germany, discusses her favourite chapters from Epigenetics in Psychiatry.
Chapter 2: Outline of Epigenetics
In Chapter 2, Bidisha Paul and Trygve O. Tollefsbol introduce the reader of Epigenetics in Psychiatry to the concept of epigenetics. The authors address in the introduction the point that a DNA sequence is not the only determining factor for phenotype among cells or organisms with an identical genotype. Heritable changes in gene function are also due to chemical changes on the nucleotides, which define the field of “epigenetics.” Tissue-specific, disease-specific, or development-status expression patterns are mediated by a variety of mechanisms involved in shaping the epigenome, such as DNA methylation, histone acetylation, and histone methylation.
The Chapter outlines the current knowledge on the following epigenetic mechanisms:
- DNA methylation. From the basic mechanistic aspects of DNA methylation, including description of the DNMT (DNA methyltransferase) family enzymes, to the role of DNA methylation in embryonic development, the authors provide the reader with a concise but comprehensive summary of this epigenetic modification. Importantly, several diseases are reported as examples of the importance of DNA methylation in development, including various malignancies as well as nervous system disorders.
- Histone modifications. Two subchapters are devoted to the mechanisms of histone acetylation and histone methylation, respectively. Different enzymes and co-factors are introduced to the reader including histone acetyltransferases (HATs), histone deacetylaces (HDACs), and histone methyltransferases (HMTs). Other histone modifications such as histone phosphorylation, ubiquitination, and sumoylation are briefly mentioned, together with interesting examples of crosstalk among different histone modifications.
- Non-Coding RNA and microRNA. The phenomena of regulation of mRNA translation and chromosome segregation via non-coding RNA (ncRNA) are introduced. Among small ncRNAs, the most important are miRNAs, siRNAs, and piRNAs, whereas snoRNAs are medium-length ncRNAs. A subchapter is devoted to a detailed description of miRNAs and their role in posttranslational gene expression regulation. Examples of specific miRNAs and lncRNAs, which play a (potential) role in carcinogenesis, stress the importance of ncRNA in health and disease.
A key message which is discussed in the subchapter “Correlation of epigenetics with epigenetics, transcriptomics and proteomics” is that an in-depth understanding of physiological biological processes and human disease can be achieved via a holistic approach in which epigenetic mechanisms will encompass the study of transcriptomics and proteomics.
Finally, clinical aspects of epigenetics are discussed in the corresponding subchapter. Key examples of diseases, varying from cancer to obesity and depression, which have been reported as being caused by alterations occurring in the epigenome are presented, together with the concept of epigenetic therapy.
Chapter 14: Epigenetics in Major Depressive Disorder
Chapter 14 of Epigenetics in Psychiatry discusses the role of epigenetics in Major Depressive Disorder (MDD). After a short introduction and information on classification and definition of major depression, Zachary A. Kaminsky addresses the brain imaging endophenotypes in MDD and the hypotheses that have been developed to explain the contribution of genetics to MDD, namely “the monoamine hypothesis” and “the neuroplasticity hypothesis.”
The author in the subchapter “Nature and nurture in MDD” explains that both genetic and environmental factors are involved in MDD, as shown by research studies in twins. However, the influence of environmental factors in MDD is much larger than the contribution of genetic background, with an estimated ratio of 7:3 (70% environmental influence, 30% genetics).
GWAS studies have suggested a few associations of polymorphisms with MDD (e.g. in BDNF and SLC6A4 genes), although causal links are difficult to establish, and various studies in the field have provided conflicting results. The author describes the idea of “missing heritability” in MDD, and names potential explanations including the emerging important role for epigenetic modifications. The main message regarding “missing heritability” in MDD is that epigenetic research seems to be vital in order to understand the interplay between genetic factors and environmental factors that leads to MDD.
In separate subchapters, Zachary A. Kaminsky summarizes important finding and explains mechanistic aspects of developmental insults on depression-relevant epigenetic modification. More specifically, developmental insults addressed are: (i) maternal diet, (ii) maternal stress, (iii) early-life adversity, (iv) gonadal hormonal fluctuation, (v) inflammation, and (vi) glucorticoid system disruptions.
Afterwards, the author presents current studies describing epigenetic patterns and correlations with brain imaging endophenotypes and certain limitations in combining epigenetics and neuroimaginig due to tissue-specificity of epigenetic patterns. Finally, a subchapter is devoted to DNA methylome scans in MDD, and candidate genes with MDD-related DNA methylation patterns are summarized by studies in rodents as well as the two – to date – genome-wide methylation studies performed in MMD.
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