دانلود رایگان مقاله انگلیسی شکل دهی سلامت روانی با تغییر ژنتیک بی رمز - الزویر 2019

Abstract

Over 98% of our genome is non-coding and is now recognised to have a major role in orchestrating the tissue specific and stimulus inducible gene expression pattern which underpins our wellbeing and mental health. The non-coding genome responds functionally to our environment at all levels, encompassing the span from psychological to physiological challenge. The gene expression pattern, termed the transcriptome, ultimately gives us our neurochemistry. Therefore a major modulator of mental wellbeing is how our genes are regulated in response to life experiences. Superimposed on the aforementioned non-coding DNA framework is a vast body of genetic variation in the elements that control response to challenges. These differences, termed polymorphisms, allow for a differential response from a specific DNA element to the same challenge thus potentially allowing ‘individuality’ in the modulation of our transcriptome. This review will focus on a fundamental mechanism defining our psychological and psychiatric wellbeing, namely how genetic variation can be correlated with differential gene expression in response to specific challenges, thus resulting in altered neurochemistry which consequently may shape behaviour.

Summary

The identification of variation in the non-coding part of the genome which affects the regulation of gene expression in part explains the often episodic nature of mental health conditions. In addition, it offers the potential for resolution of these conditions by a variety of interventions ranging from pharmaceutical to cognitive behavioural therapy which modify the signalling pathways targeting specific gene regulatory domains, modulation of the ‘stress’ driving such pathways would alter the transcriptome and hence brain chemistry, Figure 1. A prior exposure to trauma or stress could leave a molecular scar of that event, represented by an epigenetic change which alters parameters of transcriptional or post transcriptional regulation in the medium to long term [61]. It is often considered that the environmental challenge needed to affect mental health should be severe, which is not necessarily correct. For example ‘normal’ child development could also have an effect on mental health and wellbeing [23,27,33,62]. Similarly a more general approach to maintaining good mental health via diet and exercise could play a role as they could affect the cellular signalling pathways that affect mental health [63,64]. However these issues only illustrate the complexity of defining ‘life style/environment’ and its effect on our wellbeing given the complex nature of life-long experiences in defining our transcriptome, which in turn affects the neurochemistry that ultimately shapes CNS function. It’s often said that the genome is the roadmap through which ‘life style’ shapes the individual, however one can argue that the roadmap is unique for each one of us and we all have our own route to travel [65].