Depressive disorder and antidepressants from an epigenetic point of view

Abstract

Depressive disorder is a complex, heterogeneous disease that affects approximately 280 million people worldwide. Environmental, genetic, and neurobiological factors contribute to the depressive state. Since the nervous system is susceptible to shifts in activity of epigenetic modifiers, these allow for significant plasticity and response to rapid changes in the environment. Among the most studied epigenetic modifications in depressive disorder is DNA methylation, with findings centered on the brain-derived neurotrophic factor gene, the glucocorticoid receptor gene, and the serotonin transporter gene. In order to identify biomarkers that would be useful in clinical settings, for diagnosis and for treatment response, further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed. Studies on cornerstone antidepressants, such as selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, norepinephrine, and dopamine reuptake inhibitors and their effects on depressive disorder are available, but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies. In addition, two novel drugs, ketamine and esketamine, are being investigated particularly in association with treatment of resistant depression, which is one of the hot topics of contemporary research and the field of precision psychiatry.

A systematic mini-review of epigenetic mechanisms associated with electroconvulsive therapy in humans

“…These small molecules accomplish essential post-transcriptional regulatory steps of gene expression through either the degradation of an mRNA transcript or the inhibition of translation ( He and Hannon, 2004 ). Both in the peripheral and central nervous systems, miRNAs are considered potential biomarkers in the diagnosis of MDD and in monitoring therapeutic responses ( Šalamon Arèan et al, 2022 ). They regulate key processes in the central nervous system including neuronal development, neurogenesis, and synaptic plasticity, while in the periphery they are implicated with immune and endocrine regulation, for instance.…”

“…The methylation of nucleobases can change the functionality of a segment of DNA without altering the sequence. Studies have shown altered DNA methylation patterns associated with MDD and antidepressants ( Webb et al, 2020 ; Šalamon Arèan et al, 2022 ).…”

Deciphering the impact of cerebrospinal fluid on stem cell fate as a new mechanism to enhance clinical therapy development

“…As EVs can cross the BBB and later circulate in the CSF, their contents can serve as biomarkers of the pathological processes that might be happening in the brain. One of the most promising biomarkers of different neurological disorders is miRNAs, which have been identified as the cargo of EVs (Mori et al, 2019;Šalamon Arčan et al, 2023).…”

Epigenetics in psychiatry: Beyond DNA methylation

“…Studies often focus on brain regions related to emotional and behavioral responses, and cognitive and executive control functions. These often-studied regions include the limbic system (hippocampus) and the prefrontal cortex (PFC) (Brodmann area 9 in the dorsolateral PFC)[ 33 , 34 ]. Since the brain is not accessible during life, other peripheral, more easily accessible tissues, such as blood, are often included in studies of psychiatric disorders as well.…”