Are some more susceptible to epigenetic change resulting from trauma, stress because of their genes?

04 April 2014 5 9K Report

Genetics. Blood and Brains. Laura M. Zahn

Epigenetic changes, such as gene methylation, can be detected directly by examining the status of DNA within specific tissues. However, it is desirable to identify epigenetic changes from afar, especially in tissues that may be hard to survey, such as the brain. Working with a mouse model of Cushing's disease, characterized by changes in methylation as a response to exposure to glucocorticoids, Ewald et al. found that methylation and expression of the Fkpb5 gene within the hippocampus correlated with its degree of methylation in the blood. Although limited by the examination of only a single gene, the observed correlation highlights that for some diseases, it may be possible to use blood monitoring to infer epigenetic changes in the brain.

The above news just circulated by Science makes me (with no knowledge of organic chemistry) wonder if this could be the mechanism of the stress-dialysis theory of depression. That some polymorphisms (5-HTTLPR, MAOA, val/met BDNF, etc.) make the difference between a person's being able to fend off depredations of methylation? That some have an inherited acetylation defense vs. trauma, stress?

Anyway, this report sounds very useful--a biomarker for epigenetic change.

Abhishek Mukhopadhyay

There are several factors that affect epigenetic state. There is a recent article that we recently published which discusses the significant interactions and timescale separation of different events which give rise to collective epigenetic memory. Please take a look at this https://www.researchgate.net/publication/259580999_statistical_mechanics_model_for_the_dynamics_of_collective_epigenetic_histone_modification?ev=prf_pub

Article Statistical Mechanics Model for the Dynamics of Collective E...

Lucy Anne Cathcart

Sir: Thank you for circulating your exquisite work! I am pasting below reference for recent work for which I have not yet obtained access. This area of research is a whole new world to me, so promising. And yet it is so foreboding: it implies to me that trauma or stress can inflict life-time damage that can then be inherited. Would this knowledge inspire the sadists amongst us to do more than the immediate harm they inflict for their own pleasure? But to have the knowledge to stop epigenetic change leading to depression in its tracks is a tremendous inspiration.Thank you for your ongoing contribution. Lucy Anne Cathcart

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Neuroscience and Psychiatry | April 2014

Epigenetic Mechanisms of Depression

Eric J. Nestler, MD, PhD1,2

[+] Author Affiliations

JAMA Psychiatry. 2014;71(4):454-456. doi:10.1001/jamapsychiatry.2013.4291.

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Growing evidence supports the hypothesis that epigenetics is a key mechanism through which environmental exposures interact with an individual’s genetic constitution to determine risk for depression throughout life.1 Epigenetics, in its broadest meaning, refers to stable changes in gene expression that are mediated via altered chromatin structure without modification of DNA sequence. According to this hypothesis, severe stress triggers changes—in vulnerable individuals—in chromatin structure at particular genomic loci in the brain’s limbic regions, which drive sustained changes in gene expression that contribute to episodes of depression. A corollary of this hypothesis is that such stress-induced epigenetic modifications also occur early in life and help determine an individual’s lifetime vulnerability or resistance to subsequent stressful events.

Abhishek Mukhopadhyay

Thank you for your valuable input. With all due respect I mildly disagree with the following sentence of the abstract you have posted in your response -- "A corollary of this hypothesis is that such stress-induced epigenetic modifications also occur early in life and help determine an individual’s lifetime vulnerability or resistance to subsequent stressful events." In my belief, not only does epigenetic modifications occur when an offspring is in its mother's womb but it may actually begin a few generations ago. I thought you might be interested in the following videos. It might quench you curiosity to some degree.

https://www.youtube.com/watch?v=lcaQWSejufI

https://www.youtube.com/watch?v=Udlz7CMLuLQ

Lucy Anne Cathcart

Dear A. M.

Many thanks to you for helping this student towards understanding epigenetic change. Dr. Volkow's voice is inimitable and I look forward to the presentation she is introducing on the youtube link you were kind enough to furnish.

Are you in touch with Dr. Akim Etkins at Stanford? You will see he has published on this subject. Also, Dr. Lukas Pezawas, in Vienna, has been researching genetic vulnerability with fMRI evidence.

One more question for you (as if it would only be one): if someone is carrying an epigenetic change, is there a way to know this before it emerges as a suicide by that person or their offspring? It might well be that the causative trauma was not made known. I understand (I think) that the change takes place in the chromatin rather than the DNA itself, so is there a way to test for such risk factors?

Keiser University, where I am studying online is requiring me to attend at Residency this week. I am taking Dr. Archer's Epigenetic Modulation of Mood Disorders with me in case there is a chance to read it, along with Dr.Dr. Nestler's Epigenetic Mechanisms of Depression. I have a term paper due on Aug. 16-- to think you might lead me to read and write something worthy of this awe-inspiring field of knowledge. It may be that your paper will be far beyond my comprehension, but I look forward to trying to grasp it and am already grateful for your taking the time to guide me.

I do not understand about ResearchGate--is there something I can do for you about it? I simply signed in and have been very embarrassed to find myself such a beginner in the midst of such accomplished researcher/clinicians. Later, Lucy Anne

P.S. Am going to copy Dr. Pezawas, just because he has been sort of a guide post since I read his paper on 5-HTTLPR in 2005. LA

Lucy Anne Cathcart

Christmas Serendipity: Attached is a very cogent study I just had the good fortune to encounter. Last-minute throes of semester homework keep me from reading it before sending it on to you all. It is just the kind of genetic vulnerability in my question that may lead to spotting predictive factors of use in interventions to prevent and treat depression. Thanks to Dr. Gutieriez et al, and Happy New Year to you all. Lucy Anne

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