Introduction
There has long been debate over whether mental health conditions are the result of predetermined genetics, or if environmental factors are more influential. Research has shown that both genetic and environmental risk factors are key contributing causes,1,2 and it is not as simple as being one factor or the other.3 Indeed, the increasingly exciting field of epigenetics suggests that the two may play even more of an interconnected role than first thought.4
With the idea of nature vs. nurture now firmly consigned to the past, scientists are now asking the following; how is nurture affecting nature?
What Is Epigenetics?
The field of epigenetics investigates how environmental and behavioural factors can cause heritable changes in the way genes (which are made up of DNA) work, without making changes to the DNA itself.5 Epigenetic modifications, also more commonly referred to as ‘tags’ come about through environmental and behavioural causes via several different mechanisms; DNA methylation, histone modification, and non-coding RNAs.6 Although these three main mechanisms vary in action, they produce the same consequence of altering how the genetic code is read.7 This happens due to structural changes, resulting in some genes appearing to be turned ‘on’ or ‘off’.7
A great example of this is in monozygotic, or ‘identical’, twins. Whilst these pairs share the same genome, differences in an individual’s epigenome causes variations in the way their genes are expressed. Examples of this include physical attributes, such as height and weight.8 On a more sinister note, similar changes resulting from epigenetic markers can often be a cause of disease, including certain types of cancer and some metabolic disorders.9,10 These epigenetic changes that occur can be maintained from cell to cell as they divide, and in some cases, can be passed on to future generations.11
Can Trauma Be Inherited?
Over the last 50 years, epidemiological studies in Europe, Africa, and Asia have found associations between prenatal exposure to famine and a range of health conditions in later life.12,13,14 These conditions include obesity, cardiovascular disease and, with less statistical certainty, schizophrenia. In one of the most notable examples – the Dutch Hunger Winter, a famine that took place towards the end of the second world war – negative health outcomes have been found to be independent of birth weight.15 This suggests a more complex interaction between environmental factors and phenotype than first thought. Epigenetics may be an important part of this interaction.
Recent studies have looked into the possibility of trauma being inherited in multigenerational models.16,17 An epigenome-wide association study found a link between grandmaternal exposure to psychological stress during pregnancy (via intimate partner violence) and DNA-methylation in these grandchildren, suggesting DNA-methylation as a biological mechanism in the transmission of stress across several generations.16 It is important to note that due to the limited amount of research in this area, it is not possible to determine whether the effects of trauma have a favourable or unfavourable result, but only that an observable difference can be measured in this context.
Another interesting study which focused on expectant mothers who were present during the September 11th World Trade Centre Attacks in 2001 found that the mothers who developed PTSD following the event (vs. expectant mothers who did not) had lower levels of the stress hormone cortisol present in their saliva.18 More interesting still, the infant children (aged 9 months) of these mothers were also found to have lower levels of cortisol in their saliva. Reduced cortisol levels have been linked with increased vulnerability to PTSD.18 This research followed up on a similar study investigating PTSD in holocaust victims and the increased risk factor for the same illness present in their descendants (as adults), where a comparable relationship was found.19
A key limitation of studies of this nature is the large number of uncontrollable variables at play, regulated by ethical constraints. This makes it difficult to disentangle the relationship between biological and environmental factors.
Different psychiatric disorders have a range of heritabilities and epigenetics is now being considered as a mediator between the environment and genomic expression,20 suggesting that epigenetics can influence, both positively and negatively, an individual’s likelihood of developing a condition, be that physical or mental in nature.
The Epigenetic Solution
With epigenetic therapies now currently in use in other branches of medicine, namely cancer treatment,21 research into how epigenetics can aid in the treatment of mental illness is gaining momentum.
Firstly, epigenetics could provide suitable biomarkers which could be useful in the clinical diagnosis of mental illness.22 Secondly, epigenetic markers and their effects on gene expression have been found to be reversible,7 meaning that pharmacological treatments could become available as a way of treating epigenetic defects - in addition to becoming used as a preventative treatment for mental illness.23,24
From a more traditional angle, growing evidence suggests that there are epigenetic mechanisms at play which result in the beneficial effects of both psychotherapy and electroconvulsive therapy.25,26 A similar example found that exercise, and the benefits it provides to both the body and mind, can be at least partially attributed to epigenetic mechanisms.27 Nutrition is a well-established topic of study within the field of epigenetics, and it has also been demonstrated as a possible treatment option for certain psychiatric disorders.28,29 This link should come as no surprise, given the increasing research into the gut-brain axis, a current hot topic in the field of neuroscience.
How Can TVF Help?
Here at TVF, we are able to help at every step of the way, offering strategic medical advice and delivering high quality communications to help our clients achieve their goals within the healthcare sector, including in emerging fields such as epigenetics.
Our in house publications team operates at the forefront of the field with extensive experience in manuscript planning and delivery at all stages of clinical development, within a wide range of therapeutic areas. With further research and engagement opportunities, epigenetics could soon be one of the most exciting developments within medicine, of recent years.
By Saoirse Butterfield
