Antidepressant administration modulates DNA methylation induced by stress

Amanda J. Sales | Aug 2019 | Psykiatri |

Amanda J. Sales
School of Pharmaceutical
Sciences of Ribeirão Preto,
University of São Paulo,

Sâmia Joca
School of Pharmaceutical
Sciences of Ribeirão Preto,
University of São Paulo, Brazil,
Aarhus Institute of Advanced Studies (AIAS),
Aarhus University, Denmark

Major depression (MD) is a complex and debilitating psychiatric disorder that affects millions of people worldwide. Although it has been possible to treat depression for decades, depressive symptoms are only attenuated after continuous treatment for 2 to 4 weeks. One third of the patients treated with conventional antidepressants are resistant to treatment, and ⅔ do not present complete remission among the responsive patients.1,2  These findings highlight the need for a better understanding of the neurobiology of depression with the aim to provide subsidies for the development of faster and more effective treatments reducing costs and patient suffering. Epidemiological studies have demonstrated that several genetic factors can predispose to MD.3,4 On the other hand, a higher prevalence of stressful episodes in the life history of depressed individuals compared to healthy individuals is often reported, thus suggesting that stress is an important environmental factor implicated in higher risk for the development of depression.5 In fact, several lines of evidence have indicated that stress modulated the influence of genetic factors to increase vulnerability to depression.6 Epigenetics: the bridge between the environment and our genes Epigenetics refers to experience-driven changes into the chromatin structure, altering gene expression and protein coding without changing the sequence of bases of deoxyribonucleic acid, DNA.7 In addition to post-translational modifications in histone tails (eg, methylation, acetylation, phosphorylation, and ubiquitination), epigenetic mechanisms encompass covalent modifications (eg, DNA methylation), and nontranslational mechanisms of gene silencing (eg, microRNAs, miRNAs, ribonucleic acid).7  These mechanisms result in increased or decreased chromatin condensation, thus facilitating or hardening, respectively, the access of transcriptional machinery to specific promoter regions, resulting in corresponding changes in mRNA levels and protein expression changes from the same genome. DNA methylation is an epigenetic mechanism characterized by a covalent addition of a methyl group to a cytosine in cytosine-phosphate-guanine dinucleotides, resulting in...