Early life adversity, genomic plasticity, and psychopathology

Turecki, Gustavo; Ota, Vanessa Kiyomi; Belangero, Síntia Iole; Jackowski, Andrea Parolin; Kaufman, Joan

doi:10.1016/s2215-0366(14)00022-4

Cited by 132 publications

(81 citation statements)

References 41 publications

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“…The long-term effects of epigenetically moderated placenta dysfunction on health and behavior of children is clearly moderated by postnatal parenting choices, and this interaction is a rich subject for additional study (39). Even broader measures of the social environment such as neighborhoods and larger social groups appear to have some influence on methylation patterns, probably by effects on stress, although to what extent these are permanent changes is still under investigation (18,34,35,41,57,67–70). …”

Section: Evidence For Social Environmental Effects On Methylationmentioning

confidence: 99%

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DNA methylation, early life environment, and health outcomes

2015

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Epigenetics, and especially DNA methylation, have recently become provocative biological explanations for early-life environmental effects on later health. Despite the large increase in papers on the topic over the last few years, many questions remain with regards to the biological feasibility of this mechanism and the strength of the evidence to date. In this review, we examine the literature on early-life effects on epigenetic patterns, with special emphasis on social environmental influences. First, we review the basic biology of epigenetic modification of DNA and debate the role of early-life stressful, protective, and positive environments on gene-specific, system-specific, and whole-genome epigenetic patterns later in life. Second, we compare the epigenetic literatures of both humans and other animals and review the research linking epigenetic patterns to health in order to complete the mechanistic pathway. Third, we discuss physical environmental and social environmental effects, which have to date, generally not been jointly considered. Finally, we close with a discussion of the current state of the area’s research, its future direction, and its potential use in pediatric health.

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Section: Evidence For Social Environmental Effects On Methylationmentioning

confidence: 99%

“…Will measuring epigenetic changes provide a target for intervening to attenuate the health effects of environmental stressors (70,106)? We have made reference to the observation that folic acid supplementation reverses changes in DNA methylation (and RNA expression) associated with maternal protein restriction (103).…”

Section: Hurdles and Future Directionmentioning

confidence: 99%

DNA methylation, early life environment, and health outcomes

2015

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“…However, some studies pointed out to a possible gene x environment interaction in the determination of temperamental traits [70], possibly resulting in different susceptibility/resilience to current stressors (e.g., [71]). Thus, we could speculate that the rs6265 effect on St dimension may be modulated by environmental factors such as negative early life events, which are known to be more frequent in BD patients (e.g., [72]). Interestingly, the TT genotype associated with higher St levels in our study has been also associated with a superior response to treatment in BD [73].…”

Section: Discussionmentioning

confidence: 99%

Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants

et al. 2017

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Background: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. Methods: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. Results: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). Conclusion: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings.

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“…26,27 The incorporation of preclinical translational studies of fear extinction at both the behavioral and molecular level into treatments (e.g., exposure therapy and DCS) demonstrates the potential value of the integrated approach proposed by RDoC, and the burgeoning literature on neuroplasticity and epigenetics further highlights that this concern is unwarranted, as one cannot study neural circuits and genetics without considering experience. 25,28 Old dichotomies of nature versus nurture, or biology versus experience, are obsolete and have been so for decades. The dynamic interactions among genes and environment, and experience and the brain, are innumerable.…”

Section: Rdoc Matrixmentioning

confidence: 99%

The Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children

Kaufman

Gelernter

Hudziak

et al. 2015

Journal of the American Academy of Child & Adolescent Psych

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Objective The Research Domain Criteria (RDoC) project was initiated to develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures. This article reviews the rationale behind the RDoC program, its goals, and central tenets; discusses application of an RDoC framework to research with maltreated children; and highlights some clinical implications of this work. Method Published RDoC papers were reviewed, together with relevant preclinical and clinical studies that guide our work on risk and resilience in maltreated children. Results The ultimate long-term goal of the RDoC initiative is precision medicine in psychiatry. In the interim, the RDoC initiative provides a framework to organize research to help develop the database required to derive a new psychiatric nomenclature that can appropriately match treatments to patients. The primary focus of RDoC is on neural circuitry, with levels of analyses that span from molecules to behavior. There has been some concern that the RDoC framework is reductionist, with an overemphasis on neural circuits and genetics; however, the briefly reviewed, burgeoning literature on neuroplasticity and epigenetics highlights that this concern is unwarranted, as one cannot study neural circuits and genetics without considering experience. Conclusion The study of maltreated children has a number of advantages for the RDoC project, including the following: study of a subset of patients who are often not responsive to standard interventions; examination of a relatively homogenous sample with onset of psychopathology proposed to be associated with stress-related mechanisms; and well-established, relevant animal models to facilitate translational research.

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Early life adversity, genomic plasticity, and psychopathology

Cited by 132 publications

References 41 publications

DNA methylation, early life environment, and health outcomes

DNA methylation, early life environment, and health outcomes

Temperament and Character Inventory in Bipolar Disorder versus Healthy Controls and Modulatory Effects of 3 Key Functional Gene Variants

The Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in Maltreated Children

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