Epigenetics of Mental Health

Seeing that yesterday was World Mental Health Day, we are investigating the fascinating subject of how our genes affect our mental health to celebrate. 

As when it comes to anything pertaining ones’ personality and behaviour, we all know that our genetics and environment play a hand-in-hand role. Certain gene variants increase the risk of developing mental health disorders, just as circumstances in our lives do. But these intertwining factors determining our mental health go one step further, with the help of epigenetics.

Epigenetics is a genetic response to our environment, regulating the way the existing genes are expressed depending on environmental stressors. This occurs by attaching ‘bits’ such as methyl groups to our DNA, changing chromatin accessibility and modifying histones. The genetic blueprint that creates ‘you’ can be read in different ways. 

The epigenome in the brain works to maintain cell identity during environmental turmoil and adapting the brain systems to make it all function in the right way. No significant DNA methylation differences between ‘normal’ brains have been reported, but researchers have found characteristic epigenetic organisation in four brain regions that are linked to psychiatric traits. Interestingly or maybe unsurprisingly, the patterns of methylation were most different in neurons in the brain region crucial for regulating our emotional, motivation, reward and pleasure processing. 

Epigenetic changes can be positive or negative; with healthy, supportive relationships, nutritional food and good health, we can protect particularly the young from developing mental illness later in life. However, this also obviously goes the other way. Studies have shown that children who grew up in orphanages were more likely to develop anxiety in their life. 16 year olds who had experienced trauma in their life were more likely to experience psychosis by up to three times. 

Different environmental triggers, particularly during early development (even before birth), have different impacts on the epigenome – mostly modifications to DNA methylation which turns genes ‘on’ or ‘off’. When we look at depression (or really most mental health disorders), the relating epigenetic changes are thought to be triggered by severe stress especially in early childhood. This changes expression in genes involved in nervous system hyperactivity, processes of neuroplasticity, neurodegeneration and stress response. This results in a long-term vulnerability in the brain region involved in emotion and self-preservation.

Another intriguing sub-topic here is how epigenetics and the predisposition for mental illness is transgenerational. Your ancestors’ stresses may have an impact on your mental health because epigenetics can be inherited (an interesting one is children of Holocaust survivors). A study that used mice to investigate how the trauma experienced by the father influenced stress phenotypes in mice offspring showed that increased anxious-related phenotypes were found up to 3 generations down the line.

Neglect, mistreatment or any other early childhood stress favours the expression of certain genes which increase risk – not cause – of developing mental disorders. That could be later on in life or in future generations. The increasing research on the topic has also resulted in potential epigenetic treatments for mental illness.

Reading!

Neuronal brain-region-specific DNA methylation and chromatin accessibility are associated with neuropsychiatric trait heritability – Rizzardi et al.

https://www.nature.com/articles/s41593-018-0297-8

Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression – Talarowska

https://www.hindawi.com/journals/drt/2020/6357873/

Paternal transgenerational epigenetic mechanisms mediating stress phenotypes of offspring – Cunningham et al.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/ejn.14582

The potential role of epigenetic drugs in the treatment of anxiety disorders – Peedicayil

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060022/

Prenatal stress effects on offspring brain and behaviour: Mediators, alterations and dysregulated epigenetic mechanisms – Haq et al.

https://link.springer.com/article/10.1007/s12038-021-00153-7

Epigenetic transmission of Holocaust Trauma: can nightmares be inherited? – Kellermann

https://doctorsonly.co.il/wp-content/uploads/2013/07/08_Epigenetic-Transmission.pdf