Epigenetics and the glucocorticoid receptor: A review of the implications in depression

Farrell, Chloë; O’Keane, Veronica

doi:10.1016/j.psychres.2016.06.022

Cited by 65 publications

(38 citation statements)

References 55 publications

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“…In conjunction with our current results, several studies have shown that reproductive hormones, such as lactogenic hormones and thyroid function, were related to the development of PPD [14,27]. More recently, it has been proposed that hormones such as glucocorticoid cause treatment-resistant depression through epigenetic changes in the brain [28]. It is possible that different courses of PPD are due to different severities of the illness between transient and persistent PPD groups.…”

Section: Discussionsupporting

confidence: 84%

Distinct Genetic Profiles in Postpartum Depression With Different Trajectory of Illness

Takahashi

Tainaka

Nishimura

et al. 2020

Preprint

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BackgroundPostpartum depression (PPD) is a common and highly heritabledisorder in the postnatal period of new mothers. The development of PPD is shown to affectneurodevelopment in children and recent evidence suggests thatthe trajectory of PPDisalso associated with children’s neurodevelopment and mental conditions. Thus, early identification and intervention for individuals at high risk of PPD are urgently needed.Additionally, it is not clear whether genetic factors affect thetrajectory of PPD. Therefore, using a polygenic risk score (PRS) approach, we investigated if PRS for depression (Depression-PRS) and bipolar disorder (Bipolar-PRS) are associated with the development and clinical course of PPD.Methods Usingrecent large genome-wide association studies(GWAS) of depression and bipolar disorder as discovery cohorts, we calculatedDepression-PRS and Bipolar-PRS in each individual. Then, we investigated the possible association between Depression-PRS and Bipolar-PRS with the development andtrajectory of PPD insubjects from the Hamamatsu Birth Cohort for mothers and children (n = 136). Depressive symptoms were assessed using the Edinburgh Postpartum Depression Scale. Gene-set enrichment analyses were used to identify pathways underlying these conditions. ResultsDepression-PRS was significantly higher in subjects with PPD than in those without PPD(t = -3.283, P = 0.002)and logistic analysis showed that Depression-PRS significantly increases therisk of developing PPD(OR [SE] = 2.274 [0.585], P = 0.002). Furthermore, Depression-PRS was positively associated with continuity of PPD (β [SE]=1.621 [0.672]; P = 0.032).Gene-set enrichment analyses revealed that pathways such as“response to hormone”(β[SE] -2.285[1.002], P < 0.001) and “epigenetic regulation”(β[SE] 2.831 [1.317], P < 0.001) were involved in the continuity of PPD. ConclusionThese preliminary findings indicate that the genetic component plays an important role not only in the development but also inthe continuity of PPD. A polygenic risk score approach could be useful to identify subjects at risk for PPD, especially for persistent PPD,who needcareful monitoring and intervention after delivery.

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Section: Discussionsupporting

confidence: 84%

Distinct Genetic Profiles in Postpartum Depression With Different Trajectory of Illness

Takahashi

Tainaka

Nishimura

et al. 2020

Preprint

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“…Dysregulation of the hypothalamic-pituitary-adrenal axis is associated with the pathophysiology of stress-related diseases. The evidence to date supports the idea that exposure to prolonged levels of glucocorticoids stimulated by stress can induce epigenetic modifications at key regions on the gene for the glucocorticoid receptor, lead to alterations in expression and function (Farrell and O’Keane, 2016). Specific involvement of epigenetic mechanisms in modifying the glucocorticoid response in SIOH/SIG has yet to be explored.…”

Section: Future Directionsmentioning

confidence: 63%

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Fini

Schwartz

Gao

et al. 2017

Progress in Retinal and Eye Research

125

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Elevation of intraocular pressure (IOP) due to therapeutic use of glucocorticoids is called steroid-induced ocular hypertension (SIOH); this can lead to steroid-induced glaucoma (SIG). Glucocorticoids initiate signaling cascades ultimately affecting expression of hundreds of genes; this provides the potential for a highly personalized pharmacological response. Studies attempting to define genetic risk factors were undertaken early in the history of glucocorticoid use, however scientific tools available at that time were limited and progress stalled. In contrast, significant advances were made over the ensuing years in defining disease pathophysiology. As the genomics age emerged, it appeared the time was right to renew investigation into genetics. Pharmacogenomics is an unbiased discovery approach, not requiring an underlying hypothesis, and provides a way to pinpoint clinically significant genes and pathways that could not have been discovered any other way. Results of the first genome-wide association study to identify polymorphisms associated with SIOH, and follow-up on two novel genes linked to the disorder, GPR158 and HCG22, is discussed in the second half of the article. However, knowledge of genetic variants determining response to steroids in the eye also has value in its own right as a predictive and diagnostic tool. This article concludes with a discussion of how the Precision Medicine Initiative®, announced by U.S. President Obama in his 2015 State of the Union address, is beginning to touch the practice of ophthalmology. It is argued that SIOH/SIG may provide one of the next opportunities for effective application of precision medicine.

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“…Interestingly, GR α and GR β RNA levels were positively correlated with TrkB RNA levels indicating interaction between both systems, an interaction previously implicated in regulating synaptic plasticity (Jeanneteau and Chao, 2013). Although the underlying mechanisms and functional significance of such effects are still unknown, these interesting data should not be ignored especially given the roles of GR and CRHR in stress responses and stress coping (McEwen, 2007; Bosch et al, 2009, 2016; Farrell and O’Keane, 2016; Vyas et al, 2016). Second, in our present study only certain percentages of sexually naïve male and female prairie voles displayed spontaneous parental behavior towards conspecific pups, which is consistent with previous studies (Lonstein and De Vries, 2001; Ahern and Young, 2009).…”

Section: Discussionmentioning

confidence: 99%

Paternal deprivation affects social behaviors and neurochemical systems in the offspring of socially monogamous prairie voles

et al. 2017

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Early life experiences, particularly the experience with parents, are crucial to phenotypic outcomes in both humans and animals. Although the effects of maternal deprivation on offspring well-being have been studied, paternal deprivation (PD) has received little attention despite documented associations between father absence and children health problems in humans. In the present study, we utilized the socially monogamous prairie vole (Microtus ochrogaster), which displays male-female pair bonding and bi-parental care, to examine the effects of PD on adult behaviors and neurochemical expression in the hippocampus. Male and female subjects were randomly assigned into one of two experimental groups that grew up with both the mother and father (MF) or with the mother-only (MO, to generate PD experience). Our data show that MO subjects received less parental licking/grooming and carrying and were left alone in the nest more frequently than MF subjects. At adulthood (~75 days of age), MO subjects displayed increased social affiliation towards a conspecific compared to MF subjects, but the two groups did not differ in social recognition and anxiety-like behavior. Interestingly, MO subjects showed consistent increases in both gene and protein expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) as well as the levels of total histone 3 and histone 3 acetylation in the hippocampus compared to MF subjects. Further, PD experience increased glucocorticoid receptor beta (GRβ) protein expression in the hippocampus of females as well as increased corticotrophin receptor 2 (CRHR2) protein expression in the hippocampus of males, but decreased CRHR2 mRNA in both sexes. Together, our data suggest that PD has a longlasting, behavior-specific effect on social affiliation and alters hippocampal neurochemical systems in the vole brain. The functional role of such altered neurochemical systems in social behaviors and the potential involvement of epigenetic events should be further studied.

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Epigenetics and the glucocorticoid receptor: A review of the implications in depression

Cited by 65 publications

References 55 publications

Distinct Genetic Profiles in Postpartum Depression With Different Trajectory of Illness

Distinct Genetic Profiles in Postpartum Depression With Different Trajectory of Illness

Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine

Paternal deprivation affects social behaviors and neurochemical systems in the offspring of socially monogamous prairie voles

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