The early life social environment and DNA methylation

Department of Pharmacology and Therapeutics, McGill University Montreal CA, USA.
Epigenetics: official journal of the DNA Methylation Society (Impact Factor: 4.78). 08/2011; 6(8):971-8. DOI: 10.4161/epi.6.8.16793
Source: PubMed

ABSTRACT Although epidemiological data provides evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in human development; the main open question remains the mechanism. The pattern of distribution of methyl groups in DNA is different from cell-type to cell type and is conferring cell specific identity on DNA during cellular differentiation and organogenesis. This is an innate and highly programmed process. However, recent data suggests that DNA methylation is not only involved in cellular differentiation but that it is also involved in modulation of genome function in response to signals from the physical, biological and social environments. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome "adaptation" that molecularly embeds the early experiences of a child ("nurture") in the genome ("nature"). There is an emerging line of data supporting this hypothesis in rodents, non-human primates and humans that will be reviewed here. However, several critical questions remain including the identification of mechanisms that transmit the signals from the social environment to the DNA methylation/demethylation enzymes.

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    • "Childhood maltreatment has been suggested as a neurobiologically distinct subtype or 'ecophenotype,' due to the earlier onset of symptoms, symptom severity , co-morbidity, and poor treatment response associated with it (Teicher & Samson, 2013). Changes in reactivity in the hypothalamic–pituitary–adrenal (HPA) axis, reduced hippocampal volume and amygdala reactivity as well as epigenetic changes, such as DNA methylation, have been suggested as possible mechanisms for this relationship (Szyf, 2011; Teicher * Address for correspondence: E. D. "
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    ABSTRACT: To develop latent classes of exposure to traumatic experiences before the age of 13 years in an urban community sample and to use these latent classes to predict the development of negative behavioral outcomes in adolescence and young adulthood. A total of 1815 participants in an epidemiologically based, randomized field trial as children completed comprehensive psychiatric assessments as young adults. Reported experiences of nine traumatic experiences before age 13 years were used in a latent class analysis to create latent profiles of traumatic experiences. Latent classes were used to predict psychiatric outcomes at age ⩾13 years, criminal convictions, physical health problems and traumatic experiences reported in young adulthood. Three latent classes of childhood traumatic experiences were supported by the data. One class (8% of sample), primarily female, was characterized by experiences of sexual assault and reported significantly higher rates of a range of psychiatric outcomes by young adulthood. Another class (8%), primarily male, was characterized by experiences of violence exposure and reported higher levels of antisocial personality disorder and post-traumatic stress. The final class (84%) reported low levels of childhood traumatic experiences. Parental psychopathology was related to membership in the sexual assault group. Classes of childhood traumatic experiences predict specific psychiatric and behavioral outcomes in adolescence and young adulthood. The long-term adverse effects of childhood traumas are primarily concentrated in victims of sexual and non-sexual violence. Gender emerged as a key covariate in the classes of trauma exposure and outcomes.
    Psychological Medicine 07/2015; -1:1-12. DOI:10.1017/S0033291715001300 · 5.94 Impact Factor
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    • "One study investigating a subset of PTSD (child abuse-related complex PTSD) demonstrated that patient dACC volume and the hyperarousal CAPS scores were smaller in high intensity child abuse (Thomaes et al., 2010). The rACC volume has also been suggested as a marker for treatment response to cognitive behavioral therapy (Bryant et al., 2008), Moreover, there is a strong evidence that exposure to traumatic events during childhood is associated with increased incidence of psychiatric issues during adult life (Mello et al., 2010; Szyf, 2011; Mehta et al., 2013). Kessler et al. (1995) demonstrated that childhood abuse and parental psychopathology differentially predict the increased incidence and chronicity of psychiatric disorders in adults, when compared to other types of early life stressors. "
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    ABSTRACT: Background To evaluate differences in limbic structure volume of subjects exposed to urban violence during adulthood, between those who developed posttraumatic stress disorder (with PTSD) and resilient matched controls (without PTSD). Methods Limbic volumetric measures of 32 subjects with PTSD and 32 subjects without PTSD who underwent brain MRI were analyzed in an epidemiological study in the city of Sao Paulo. The hippocampus, amygdala, cingulate, and parahipocampal gyri volumes were estimated using FreeSurfer software. We also investigated the association between limbic volumetric measurements, symptom´s severity, and early life stress history (measure by Early Trauma Inventory – ETI). Results Subjects with PTSD presented reduced volume of the right rostral part of the anterior cingulate, compared to subjects without PTSD, after controlling for intracranial volume, ETI, and depressive symptoms. Subjects with PTSD presented larger bilateral hippocampus and right amygdala, but secondary to the higher ETI. In PTSD group there was a positive correlation between ETI with bilateral hippocampus, bilateral amygdala, and left parahippocampus. Limitations First, the cross-sectional study design precludes causal interpretation of limbic structure reduction in PTSD, consequence of PTSD, or other life events. Finally, since the sample size was not sufficiently large, we could not observe whether or not limbic structure volume could be related to the type of trauma. Conclusions The present study provides evidence of a reduced anterior cingulate volume in subjects with PTSD than in resilient subjects exposed to urban violence. Enlargement of hippocampus and amygdala volume was observed in subjects with PTSD, however secondary to early trauma experience.
    Journal of Affective Disorders 10/2014; 168:13–20. DOI:10.1016/j.jad.2014.06.036 · 3.38 Impact Factor
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    • "epigenetics) will be assessed. Through DNA methylation, environmental experiences regulate gene expression, which may induce lasting changes in stress reactivity [91,92]. Differential levels of DNA methylation of genes related to stress reactivity have already been associated with PTSD and early life stress [93-95]. "
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    ABSTRACT: Currently few evidence based interventions are available for the prevention of PTSD within the first weeks after trauma. Increased risk for PTSD development is associated with dysregulated fear and stress responses prior to and shortly after trauma, as well as with a lack of perceived social support early after trauma. Oxytocin is a potent regulator of these processes. Therefore, we propose that oxytocin may be important in reducing adverse consequences of trauma. The 'BONDS' study is conducted in order to assess the efficacy of an early intervention with intranasal oxytocin for the prevention of PTSD. In this multicenter double-blind randomized placebo-controlled trial we will recruit 220 Emergency Department patients at increased risk of PTSD. Trauma-exposed patients are screened for increased PTSD risk with questionnaires assessing peri-traumatic distress and acute PTSD symptoms within 7 days after trauma. Baseline PTSD symptom severity scores and neuroendocrine and psychophysiological measures will be collected within 10 days after trauma. Participants will be randomized to 7.5 days of intranasal oxytocin (40 IU) or placebo twice a day. Follow-up measurements at 1.5, 3 and 6 months post-trauma are collected to assess PTSD symptom severity (the primary outcome measure). Other measures of symptoms of psychopathology, and neuroendocrine and psychophysiological disorders are secondary outcome measures. We hypothesize that intranasal oxytocin administered early after trauma is an effective pharmacological strategy to prevent PTSD in individuals at increased risk, which is both safe and easily applicable. Interindividual and contextual factors that may influence the effects of oxytocin treatment will be considered in the analysis of the results.Trial registration: Netherlands Trial Registry: NTR3190.
    BMC Psychiatry 03/2014; 14(1):92. DOI:10.1186/1471-244X-14-92 · 2.21 Impact Factor
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