Sex Differences in Dna Methylation May Contribute to Risk of PTSD and Depression: A Review of Existing Evidence

Uddin, Monica; Sipahi, Birsen; Li, Jia; Koenen, Karestan C.

doi:10.1002/da.22167

Cited by 54 publications

(38 citation statements)

References 77 publications

(150 reference statements)

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“…Thus, controlling for many but yet same factors in both genders in the current study may result in the apparent different associations between genders. Another explanation may be that distinct between-gender patterns of epigenetic mechanisms exist in response to early life experiences, as has been previously suggested in relation to other late-life outcomes (Uddin et al 2013). …”

Section: Discussionmentioning

confidence: 83%

Childhood conditions and current physical performance among non-institutionalized individuals aged 50+ in Israel

Weinstein

2016

Eur J Ageing

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Adverse socioeconomic conditions in childhood have been previously linked with high risk of various health conditions. However, the association with future physical function has been less studied. Hand grip strength and chair-rising time are objective measures of physical capability indicating current and future health outcomes. The aim of this study was to test the hypothesis that perceived socio-economic status in childhood is related to current measures of physical function, among Israeli participants of the Survey of Health, Ageing and Retirement in Europe project. The study included 2300 participants aged 50 years or older (mean age 68 ± 10; 56 % women). Generalized linear regression models were used to examine the associations of childhood wealth and number of books in residence with grip strength and time to complete five rises from a chair. Logistic regression models were used to assess the relationships between the early life conditions and the ability to perform the physical tests. Adjustment was made for current income or household wealth, and for demographic, anthropometric, health, and life-style measures. Being wealthy and having a large number of books at home in childhood was associated with a stronger hand grip and a better chair-rise test performance. These associations were more robust in women compared to men, and persisted after adjustment for potential covariates. In addition, childhood wealth and number of books were associated with lower risk of being unable to perform the tests. Thus, early-life programming may contribute to physical function indicators in mid- and late-life.

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Section: Discussionmentioning

confidence: 83%

Childhood conditions and current physical performance among non-institutionalized individuals aged 50+ in Israel

Weinstein

2016

Eur J Ageing

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“…There is a relative lack of information about epigenetic differences in the brains of males versus females [106, 107] and how such differences may contribute to sexually dimorphic risk for emotional dysfunction [108]. Thus, it will be important for future studies to determine whether both male and female individuals with high versus low propensity to an anxiety/depression-like phenotype display similar or unique differences in the limbic transcriptome and how those differences may impact behavioral outcomes.…”

Section: Discussionmentioning

confidence: 99%

Genetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala

McCoy

Jackson

Day

et al. 2017

Behavioural Brain Research

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Understanding biological mechanisms that shape vulnerability to emotional dysfunction is critical for elucidating the neurobiology of psychiatric illnesses like anxiety and depression. To elucidate molecular and epigenetic alterations in the brain that contribute to individual differences in emotionality, our laboratory utilized a rodent model of temperamental differences. Rats bred for low response to novelty (Low Responders, LRs) are inhibited in novel situations and display high anxiety, helplessness, and diminished sociability compared to High Novelty Responder (HR) rats. Our current transcriptome profiling experiment identified widespread gene expression differences in the amygdala of adult HR/LR rats; we hypothesize that HR/LR gene expression and downstream behavioral differences stem from distinct epigenetic (specifically DNA methylation) patterning in the HR/LR brain. Although we found similar levels of DNA methyltransferase proteins in the adult HR/LR amygdala, next-generation sequencing analysis of the methylome revealed 793 differentially methylated genomic sites between the groups. Most of the differentially methylated sites were hypermethylated in HR versus LR, so we next tested the hypothesis that enhancing DNA methylation in LRs would improve their anxiety/depression-like phenotype. We found that increasing DNA methylation in LRs (via increased dietary methyl donor content) improved their anxiety-like behavior and decreased their typically high levels of Forced Swim Test (FST) immobility; however, dietary methyl donor depletion exacerbated LRs’ high FST immobility. These data are generally consistent with findings in depressed patients showing that treatment with DNA methylation-promoting agents improves depressive symptoms, and highlight epigenetic mechanisms that may contribute to individual differences in risk for emotional dysfunction.

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“…Epigenetic modifications may be a mechanistic link between maternal adversity and infant and child outcomes [35, 129]. Work in animal models, and a more limited but growing literature in human studies, demonstrates that epigenetic changes occur in response to environmental stress, some in a sex-specific manner [130]. Evidence of epigenetic modification within HPA pathways [131, 132], including the glucocorticoid receptor [133] and the serotonin transporter [134] have been identified in human offspring.…”

Section: Ppd and Anxiety As A Risk Factor For Depression And Anxiementioning

confidence: 99%

Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures

Babb¹,

Deligiannidis²,

Murgatroyd³

et al. 2015

Behavioural Brain Research

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Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety.

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Sex Differences in Dna Methylation May Contribute to Risk of PTSD and Depression: A Review of Existing Evidence

Cited by 54 publications

References 77 publications

Childhood conditions and current physical performance among non-institutionalized individuals aged 50+ in Israel

Childhood conditions and current physical performance among non-institutionalized individuals aged 50+ in Israel

Genetic predisposition to high anxiety- and depression-like behavior coincides with diminished DNA methylation in the adult rat amygdala

Peripartum depression and anxiety as an integrative cross domain target for psychiatric preventative measures

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