The Relationship between DNA Methylation and Antidepressant Medications: A Systematic Review

Abstract

Major depressive disorder (MDD) is the leading cause of disability worldwide and is associated with high rates of suicide and medical comorbidities. Current antidepressant medications are suboptimal, as most MDD patients fail to achieve complete remission from symptoms. At present, clinicians are unable to predict which antidepressant is most effective for a particular patient, exposing patients to multiple medication trials and side effects. Since MDD’s etiology includes interactions between genes and environment, the epigenome is of interest for predictive utility and treatment monitoring. Epigenetic mechanisms of antidepressant medications are incompletely understood. Differences in epigenetic profiles may impact treatment response. A systematic literature search yielded 24 studies reporting the interaction between antidepressants and eight genes (BDNF, MAOA, SLC6A2, SLC6A4, HTR1A, HTR1B, IL6, IL11) and whole genome methylation. Methylation of certain sites within BDNF, SLC6A4, HTR1A, HTR1B, IL11, and the whole genome was predictive of antidepressant response. Comparing DNA methylation in patients during depressive episodes, during treatment, in remission, and after antidepressant cessation would help clarify the influence of antidepressant medications on DNA methylation. Individuals’ unique methylation profiles may be used clinically for personalization of antidepressant choice in the future.

The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats

“…Previous studies showed that the expression and activity of DNA methyltransferases were increased in patients with depression. In the case of animals exposed to stress stimuli, studies confirmed that the level of DNA methyltransferases was increased in the prefrontal cortex and hippocampus (Nagy et al 2018 ; Webb et al 2020 ). The effectiveness of antidepressants may also be associated with differential methylation of the CYP450 enzymes of the liver which metabolize antidepressant drugs.…”

The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy

“…Epigenetics refers to modifiable, potentially heritable, non-nucleotide changes to DNA transcription which are essential for normal cell differentiation and neurogenesis [ 99 ]. These changes can both be stable over time and dynamically responsive to environmental challenges such as nutritional, pharmacological, physical, and psychosocial changes, providing experience-dependent DNA modulation.…”

“…The second mechanism consists of post-translational modifications of histone proteins, such as methylation, phosphorylation, and acetylation, which alter DNA that bind to regulatory proteins as well as the availability of chromatin for transcriptional activity. The third mechanism comprises RNAs (including siRNAs, miRNAs, and piRNAs) and long noncoding RNAs, which also regulate gene expression [ 99 , 101 , 102 , 103 , 104 ].…”

Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior

“…However, even though many theories suggest that the early life stress can affect the adult emotions and behaviors in a long run, but the underlying neural mechanism is far from clear. Since the etiology of MDD includes the interaction between genes and the environment, epigenetics is important for predicting utility and treatment monitoring (Webb et al, 2020). Stressful life experiences, especially early life stress, might carry out epigenetic modification of these risk genes via DNA methylation and microRNAs (miRNAs) regulation, and the expression of these genes will have long-lasting effects, which will lead to changes in brain structure and function (Pishva et al, 2017;Ding and Dai, 2019).…”

“…Stressful life experiences, especially early life stress, might carry out epigenetic modification of these risk genes via DNA methylation and microRNAs (miRNAs) regulation, and the expression of these genes will have long-lasting effects, which will lead to changes in brain structure and function (Pishva et al, 2017;Ding and Dai, 2019). In addition, the epigenetic differences may affect treatment response (Webb et al, 2020), however, the epigenetic mechanism of antidepressant drugs is not fully understood.…”