Decades of research has shown that genetics greatly contribute to the development of a psychiatric disorder.
This contribution reaches up to 40 to 80% at most extreme cases.
However, heritability doesn’t seem to be sufficient to explain the whole story.
It seems that environmental factors shape our genes and help explain the rest of it. Facing childhood adversity, being exposed to stressors, our diet etc can be classified as such.
These non-genetic factors seem to modulate gene function in such a way that a normally functioning gene becomes inactive or the opposite happens, a gene that is normally not expressed, becomes active and starts making proteins.
But how can it happen? What are the molecular mechanisms controlling gene expression?
Research has suggested that this interaction between genetic and environmental factors can be explained by epigenetic mechanisms.
Epigenetic mechanisms are chemical alterations causing changes in gene function without a change in the DNA sequence itself.
These changes usually occur in DNA, histones or non-coding RNAs.
In this way, gene regulation is modulated by interference with transcription and translation.
By definition, these alterations can be transmitted to feature generations.
Nevertheless, more importantly, unlike genetic changes such as mutations, epigenetic mechanisms are reversible.
Epigenetic Mechanisms in Psychopathology
To this day, many different kinds of psychiatric disorders have been associated with epigenetic alterations in both animal and human studies.
For instance, increased methylation of glucocorticoid receptor (GR) gene, NR3C1, was found to be associated with negative life events and psychopathology in many studies. Methylation of glucocorticoid receptor gene was found to predict childhood maltreatment, according to a 2017 study.
Methylation of this gene decreases its expression. This results in less glucocorticoid receptor on the cell membrane, leading to an inadequate stress response. As a result, the individuals become more susceptible to stress related disorders.
Epigenetic Mechanisms in Psychotherapy
The good news is that such epigenetic alterations are shown to be reversed by treatment.
In a 2013 study conducted with patients having post-traumatic stress disorder, FKBP5 gene methylation was shown to decline in responders after 12-week exposure therapy. More importantly, in non-responders, the methylation increased.
Protein of this gene acts as a co-chaperone of glucocorticoid receptor, and thus required for its normal functioning. When the promoter of this gene is hypermethylated, there is not sufficient protein to regulate GR, resulting in insufficient stress response. In this case, psychotherapy helps reverse this dysregulation.
The fact that the pathogenesis of psychiatric disorders involve many genes and proteins, and all these can be chemically altered and might stop functioning one day just like that!..
might as well be considered as an advantage for the prevention and treatment.
This tells us that if a pathology can develop as a result of life events, it can also be reversed with intervention.
As these interventions can be psychopharmacological or psychotherapeutic, they can also be simply teaching coping skills or providing social support depending on the condition.
Even certain supplementations such as S-adenosylmethionine (SAMe) and l-methylfolate are suggested to be used as augmenting agents in certain psychiatric disorders. Through their action of methyl donation, they are regarded as having a potential to change the epigenome.
In the future, this all might lead to the development and use of drugs such as histone deacetylase (HDAC) or DNA methyltransferase (DNMT) inhibitors that can modify epigenetic mechanisms directly, and more effectively.
Thank you for reading.
Parent, J., Parade, S. H., Laumann, L. E., Ridout, K. K., Yang, B. Z., Marsit, C. J., … Tyrka, A. R. (2017). Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment. Development and Psychopathology, 29, 1635–1648.
Peedicayil, J. (2012). Role of epigenetics in pharmacotherapy, psychotherapy and nutritional management of mental disorders. Journal of Clinical Pharmacy and Therapeutics, 37, 499–501.
Yehuda, R., Daskalakis, N. P., Desarnaud, F., Makotkine, I., Lehrner, A. L., Koch, E., … Bierer, L. M. (2013). Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Frontiers in Psychiatry, 4, 118.