Epigenetics is the study of heritable changes in the genome or phenotype of an organism that do not involve direct alteration of the DNA sequence itself, but involve changes or alterations in rates of gene activity or gene expression [1] . Many factors, such as stress, environment changes, and psychoactive substance consumption habits, influence gene expression throughout an organism's life, and studies are starting to show potential relevance of gene expression on the presence and severity of psychiatric disorders. Recent work has shown the absence or presence of childhood abuse to have influence on the methylation, a common marker of altered DNA activity, state of multiple protein coding sites, including 5-HT3A receptors, Brain-derived Neurotrophic Factor (BDNF), and glucocorticoid receptors [2, 3, 4], and that the altered methylation of these sites as been seen to be correlated with the severity of psychiatric disorders such as Attention Deficit Hyperactivity Disorder (ADHD), borderline personality disorder, bipolar disorders [2, 3, 4], which higher rates of methylation of these receptors being tied with a higher severity for the disorder. There is also evidence that stressful or traumatic experiences, such as those leading to Post Traumatic Stress Disorder (PTSD), may have a genome wide influence on DNA methylation,, and that the degree of methylation is correlated with the severity of the PTSD [5]. It is noted that the increased methylation of certain protein coding sites could lead to an increase in the expression of these specific proteins, and that increased translation - especially of neurotransmitter receptors such as seritenergic (5-HT) and dopaminergic (DA) could have behavioral influence impacting reward and drug-seeking behavior[8]. These transmitter systems hold interest specifically on counteracting psychopathologies influenced by altered activity of certain brain regions of circuits, such as depression. Molecular biology is providing many new and useful tools for aiding in the understanding of psychopathologies, including developing biomarkers for psychiatric disorders through the use of genome-wide association studies (GWAS), a technique that uses large data bases of genetic information to draw correlations dependent on gene presence/expression, and psychiatric genetics [6]. One large area of research in the field of psychiatric genetics is the influence of copy number variation, specifically single-nucleotides polymorphisms (SNPs), of target genes influence the severity and presence of psychiatric disorders [7]. While many of the systems neurobiological systems in question are complex, as our understanding of the circuitry involved in these conditions such as depression, PTSD, and ADHD increases, we can better create methods to target specific genes of interest, and ask better questions about how alterations in these genes influence the severity of symptoms.
Sources: [1] Dupont C, Armant DR, Brenner CA (September 2009). "Epigenetics: definition, mechanisms and clinical perspective". Seminars in Reproductive Medicine. 27 (5): 351–7. doi:10.1055/s-0029-1237423. PMC 2791696. PMID 19711245. [2] Perroud N, Zewdie S, et al. Methylation of serotonin receptor 3A in ADHD disorder, borderline personality disorder, and bipolar disorders: link with the severity of the disorders and childhood maltreatment. Depression and Anixeity 2016;33: 45-55 [3] Perroud N, Paoloni-Giacobino A, Prada P, et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry 2011;1:e59. [4] Thaler L, Gauvin L, Joober R, et al. Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry 2014;54:43–49. [5] Mehta D, Klengel T, Conneely KN, et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci U S A 2013;110(2):8302– 8307. [6] Burmeister M, McInnis MG, Zöllner S (2008). "Psychiatric genetics: progress amid controversy". Nat Rev Genet. 9 (7): 527–40. doi:10.1038/nrg2381. PMID 18560438. [7] Bourgeron, T., Giros, B.,(2003). " Genetic Markers in Psychiatric Genetics". In Leboyer, M, Bellivier, F. Psychiatric genetics: methods and reviews. Humana Press. pp. 63–98 [8] Kondo M, Nakamura Y, Ishida Y, Shimada S. The 5-HT receptor is essential for exercise-induced hippocampal neurogenesis and antidepressant effects. Mol Psychiatry 2014, doi: 10.1038/mp.2014.153
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