Understanding the epigenetic basis of sex differences in depression

Abstract

Epigenetics refers to potentially heritable processes that can mediate both lasting and transient changes in gene expression in the absence of genome sequence alterations. The field of epigenetics has introduced a novel understanding of the mechanisms through which the environment can shape an individual and potentially its offspring. This review examines the current literature exploring the role of epigenetics in the development of mood disorders such as depression. Depression is ~2-fold more common in females, yet the majority of pre-clinical research has been conducted exclusively in male subjects. Here we discuss what is known about sex differences in epigenetic regulation and function and how this may contribute to the etiology and onset of mood disorders.

Interface between social support, quality of life and depression in users eligible for palliative care

“…Regarding the association between depression symptoms and female patients, a study conducted to investigate the association between genetic factors and depression pointed out that women are on average twice as likely as men to have episodes of depression. However, despite the existence of justifications related to genetic, neuro-hormonal and psychobiological aspects, it is believed that due to the lack of data regarding the actual number of patients affected by this clinical diagnosis, investigations about the characteristics of this disease are limited, thereby highlighting the importance of new studies on this prevalence in the present day (23) .…”

Translational identification of transcriptional signatures of major depression and antidepressant response

“…The majority of rodent studies involving behavioral analyses used male rodents, despite a higher prevalence of MDD in women. Future investigations will require the inclusion of both sexes in animal testing (Hodes et al, 2017), but it is interesting to note that in a mouse model of depression during menopause, Miyata et al (2016b) also found that the gene expression alterations induced by ovariectomy were mainly associated with ribosomal and mitochondrial functions in both the medial prefrontal cortex and the blood, strengthening the results we discussed above. We also only addressed the response to antidepressant treatment with a single drug, fluoxetine, while other drugs with different selectivity for neurotransmitters other than serotonin are frequently used in the clinic (Bagot et al, 2017).…”

Gene regulatory mechanisms underlying sex differences in brain development and psychiatric disease

“…Increasing evidence supports a role for epigenetic changes in the pathogenesis of depression, particularly in response to early life stress. The interactions with stress signaling and the pathways for sex differentiation suggest a mechanism by which the activation of stress pathways may act sex‐specifically to control the response to chronic stress . These findings are supported at the gene regulatory level by recent studies on cross talk between SRs and glucocorticoid receptor (GR).…”

“…Women have twice the lifetime risk of developing depression compared with men and appear to experience symptoms that are more severe and diverse . Like many other major neuropsychiatric conditions, major depressive disorder typically evolves during early adolescence, with an earlier and distinct presentation in girls compared with boys . This suggests that sex‐specific pathways that regulate mood are activated by the onset of puberty and may intersect with stress response pathways to contribute to gender‐specific symptoms …”