3.7.5 Epigenetics

Epigenetics

Epigenetics is a field of biology that studies changes in gene expression or cellular phenotype that do not involve changes to the underlying DNA sequence. In psychiatry, epigenetics has been studied as a potential mechanism to explain the development of various mental illnesses, such as depression, schizophrenia, and bipolar disorder. The term “epigenome” refers to the collection of all epigenetic alterations in a genome.

There is evidence that environmental factors, such as stress, abuse, and nutrition, can lead to epigenetic changes that alter gene expression and contribute to the development of mental illness. For example, early life stress has been shown to result in epigenetic changes in the brain that increase the risk of developing depression later in life. Similarly, epigenetic changes in the gene responsible for regulating the levels of brain-derived neurotrophic factor (BDNF) have been associated with the development of depression and schizophrenia.

Another example of the role of epigenetics in psychiatry is the field of pharmacogenomics, which examines the role of genetic and epigenetic factors in determining an individual’s response to medication. By understanding the epigenetic changes associated with different mental illnesses, researchers hope to develop more personalized and effective treatments for mental health conditions.

However, the field of epigenetics in psychiatry is still in its early stages, and more research is needed to fully understand the complex interplay between genetics, environment, and epigenetics in the development of mental illness. Nevertheless, the study of epigenetics in psychiatry holds great promise for the development of new and innovative treatments for mental health conditions.

DNA methylation and histone modification are two key mechanisms of epigenetic regulation that control gene expression and cellular phenotype.

DNA methylation:

DNA methylation refers to the addition of a methyl group to the DNA molecule, which typically occurs at the cytosine residue in a CpG dinucleotide context. DNA methylation can result in the suppression of gene expression and has been implicated in the development of various diseases, including cancer and mental illness.

Attaches to specific locations on the DNA strand using chemical groups. These chemical compounds prevent proteins from binding to DNA and “reading” it. Demethylation is the removal of chemical groups. During demethylation, genes are “on,” whereas during methylation, they are “off” (Bird, 2002).

Histone modification:

Histone modification refers to the covalent modification of the histone proteins that package DNA into a compact structure called chromatin. The modification of histones, such as acetylation, methylation, and phosphorylation, can change the structure and stability of chromatin and regulate gene expression. For example, acetylation of histones is generally associated with an open chromatin structure and increased gene expression, while methylation of histones can result in a closed chromatin structure and reduced gene expression.

Whether a gene is “on” or “off” depends on how tightly the histones are packed. The gene remains dormant because tightly packed histones prohibit proteins from attaching to the DNA. Histones that are not tightly packed enable proteins to attach to DNA more readily, activating the gene. It is possible to add or remove chemical groups to change how tightly or loosely the histones are packed, so activating or deactivating the genes (Strahl, 2000).

Together, DNA methylation and histone modification constitute a complex interplay of epigenetic mechanisms that regulate gene expression and cellular phenotype in response to various environmental and genetic factors. Understanding the regulation of DNA methylation and histone modification is important for developing new treatments for various diseases and disorders, including mental illness and cancer (Jenuwein, 2001).

Causes of Epigenetics:

Different factors can affect epigenetic changes.

Effect of Epigenetics:

Endogenous hormones, the environment, ageing, food, and exposure to endocrine-disrupting substances (EDCs) are some of the factors that can modify an individual’s epigenome, and the impacts of these changes can be passed down through generations. Without changing the DNA sequence, itself, epigenetic alterations to the genome can change the phenotype of the individual. DNA methylation, histone changes, and aberrant microRNA (miRNA) production are examples of epigenetic modifications that start during the formation of germ cells and embryogenesis and last all the way up to death. Hormone regulation happens as we age as a result of epigenetic changes. The epigenome of the foetus can be impacted by maternal undernutrition or overnutrition, and the results can last a lifetime. Additionally, mother care during the offspring’s childhood can result in distinct phenotypes seen in adults. Epigenetic alterations have been linked to endocrine system-controlled illnesses like obesity and diabetes as well as female infertility. These traits can be observed not only in F1 but also in F3, as some chemical impacts can be transmitted through the germline and have an impact across generations (Sharma et al., 2010).

The effects of epigenetics can be wide-ranging and have significant implications for various biological processes, including development, ageing, and disease. Some of the key effects of epigenetics include:

1. Gene expression regulation: Epigenetic modifications, such as DNA methylation and histone modification, can regulate gene expression and control the activation or repression of specific genes.
2. Development: Epigenetic modifications play a crucial role in the development of an organism, including the differentiation of cells into specific cell types and the formation of tissues and organs.
3. Inheritance of traits: Epigenetic modifications can be passed down from one generation to the next and can contribute to the inheritance of specific traits, such as susceptibility to certain diseases.
4. Environmental responses: Epigenetic modifications can be induced by various environmental factors, such as stress, diet, and exposure to toxins, and can have long-lasting effects on an individual’s health and well-being.
5. Disease development: Epigenetic modifications have been implicated in the development of a wide range of diseases, including cancer, cardiovascular disease, and mental illness.
6. Ageing: Epigenetic modifications can contribute to the ageing process and the development of age-related diseases.

Overall, the effects of epigenetics are complex and multifaceted, and a better understanding of the mechanisms of epigenetic regulation is crucial for developing new and innovative treatments for various diseases and disorders.

How Drugs, Psychotherapy, and Good/Adverse Experiences can Modify Epigenetics

Drugs, psychotherapy, and experiences can modify epigenetics through their effects on gene expression and cellular phenotype.

1. Drugs: Some drugs, such as antipsychotics, antidepressants, and mood stabilizers, have been shown to affect epigenetic mechanisms, such as DNA methylation and histone modification, to regulate gene expression and treat mental illness. For example, some antidepressants have been shown to reverse epigenetic changes associated with depression, suggesting a potential mechanism for their therapeutic effects.
2. Psychotherapy: Psychotherapy has also been shown to have epigenetic effects. For example, studies have shown that cognitive behavioural therapy and mindfulness-based therapies can modify epigenetic markers and alter gene expression in the brain, suggesting that these therapies may have beneficial effects on mental health by modulating epigenetic mechanisms.
3. Good experiences: Positive experiences, such as social support, exercise, and a healthy diet, can have beneficial effects on epigenetics. For example, physical exercise has been shown to modify DNA methylation and histone modification, resulting in changes in gene expression that improve brain function and reduce the risk of mental illness (Bales, 2015) (Boos, 2015).
4. Adverse experiences: On the other hand, adverse experiences, such as childhood abuse, stress, and poor nutrition, can have negative effects on epigenetics. For example, early life stress has been shown to result in epigenetic changes in the brain that increase the risk of developing depression later in life (Miller, 2010).

Overall, these examples demonstrate how drugs, psychotherapy, and experiences can modify epigenetics and have significant implications for mental health and well-being. The study of these mechanisms is still in its early stages, but it holds great promise for the development of more personalized and effective treatments for mental illness.

References:

(1) Bales, K. L., Capitanio, J. P., & Mason, W. A. (2015). Social environmental enrichment modifies DNA methylation and gene expression in the brain. Brain research, 1617, 18-27.

(2) Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes & Development, 16(1), 6-21.

(3) Roos, J., Skånland, S. S., Anesten, F., Johansson, S., Sääf, M., & Abrahamsson, L. (2015). Exercise prevents stress-induced changes in DNA methylation. Molecular psychiatry, 20(7), 847-853.

(4) Jenuwein, T., & Allis, C. D. (2001). Translating the histone code. Science, 293(5532), 1074-1080.

(5) Miller, G. E., & Chen, E. (2010). Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving toward a model of behavioral and biological mechanisms. Psychological bulletin, 136(6), 853-857.

(6) Strahl, B. D., & Allis, C. D. (2000). The language of covalent histone modifications. Nature, 403(6765), 41-45.