Epigenetics and gene expression profile in first-episode psychosis: The role of childhood trauma

Tomassi, Simona; Tosato, Sarah

doi:10.1016/j.neubiorev.2017.10.018

Cited by 48 publications

(33 citation statements)

References 69 publications

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“…Moreover, Met carriers exposed to childhood sexual abuse showed reduced right hippocampus volume (Aas et al, 2013), suggesting negative effects on neuroplasticity in the brain. On an epigenetic level, a recent review concluded that childhood trauma was associated with global DNA hypomethylation and reduced BDNF gene-expression in first-episode psychosis subjects (Tomassi and Tosato, 2017). However, the literature on gene–environment relationship in the etiology of psychosis is rather heterogeneous as the results from candidate gene studies could quite frequently not be replicated (Zwicker et al, 2018).…”

Section: Interaction Of Childhood Trauma With Genetic Factorsmentioning

confidence: 99%

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

et al. 2019

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Schizophrenia is a severe neuropsychiatric disorder with persistence of symptoms throughout adult life in most of the affected patients. This unfavorable course is associated with multiple episodes and residual symptoms, mainly negative symptoms and cognitive deficits. The neural diathesis-stress model proposes that psychosocial stress acts on a pre-existing vulnerability and thus triggers the symptoms of schizophrenia. Childhood trauma is a severe form of stress that renders individuals more vulnerable to developing schizophrenia; neurobiological effects of such trauma on the endocrine system and epigenetic mechanisms are discussed. Childhood trauma is associated with impaired working memory, executive function, verbal learning, and attention in schizophrenia patients, including those at ultra-high risk to develop psychosis. In these patients, higher levels of childhood trauma were correlated with higher levels of attenuated positive symptoms, general symptoms, and depressive symptoms; lower levels of global functioning; and poorer cognitive performance in visual episodic memory end executive functions. In this review, we discuss effects of specific gene variants that interact with childhood trauma in patients with schizophrenia and describe new findings on the brain structural and functional level. Additive effects between childhood trauma and brain-derived neurotrophic factor methionine carriers on volume loss of the hippocampal subregions cornu ammonis (CA)4/dentate gyrus and CA2/3 have been reported in schizophrenia patients. A functional magnetic resonance imaging study showed that childhood trauma exposure resulted in aberrant function of parietal areas involved in working memory and of visual cortical areas involved in attention. In a theory of mind task reflecting social cognition, childhood trauma was associated with activation of the posterior cingulate gyrus, precuneus, and dorsomedial prefrontal cortex in patients with schizophrenia. In addition, decreased connectivity was shown between the posterior cingulate/precuneus region and the amygdala in patients with high levels of physical neglect and sexual abuse during childhood, suggesting that disturbances in specific brain networks underlie cognitive abilities. Finally, we discuss some of the questionnaires that are commonly used to assess childhood trauma and outline possibilities to use recent biostatistical methods, such as machine learning, to analyze the resulting datasets.

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Section: Interaction Of Childhood Trauma With Genetic Factorsmentioning

confidence: 99%

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

et al. 2019

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“…Similarly, there was a bidirectional regulation of methylation in the cingulate cortex of those with/without childhood trauma who has had depression and died by suicide, with the highest differential methylation occurring in genes that related to myelin (103). In a 2017 systematic review of epigenetic associations with childhood trauma in first episode psychosis patients and healthy individuals, childhood trauma was associated with global hypomethylation in peripheral blood samples (104, 105).…”

Section: The Associations Between Genetic and Epigenetic And Childhoomentioning

confidence: 99%

Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma

et al. 2019

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Adverse childhood experiences (ACEs) may be referred to by other terms (e.g., early life adversity or stress and childhood trauma) and have a lifelong impact on mental and physical health. For example, childhood trauma has been associated with posttraumatic stress disorder (PTSD), anxiety, depression, bipolar disorder, diabetes, and cardiovascular disease. The heritability of ACE-related phenotypes such as PTSD, depression, and resilience is low to moderate, and, moreover, is very variable for a given phenotype, which implies that gene by environment interactions (such as through epigenetic modifications) may be involved in the onset of these phenotypes. Currently, there is increasing interest in the investigation of epigenetic contributions to ACE-induced differential health outcomes. Although there are a number of studies in this field, there are still research gaps. In this review, the basic concepts of epigenetic modifications (such as methylation) and the function of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response are outlined. Examples of specific genes undergoing methylation in association with ACE-induced differential health outcomes are provided. Limitations in this field, e.g., uncertain clinical diagnosis, conceptual inconsistencies, and technical drawbacks, are reviewed, with suggestions for advances using new technologies and novel research directions. We thereby provide a platform on which the field of ACE-induced phenotypes in mental health may build.

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“…We examined the effect of seven adversities shown previously to associate with epigenetic marks (46)(47)(48): (a) caregiver physical or emotional abuse (49)(50)(51)(52); (b) sexual or physical abuse (by anyone) (49)(50)(51)(52); (c) maternal psychopathology (53,54); (d) one adult in the household (55); (e) family instability (56,57); (f) financial stress/poverty (58,59); and (g) neighborhood disadvantage/poverty (60). Each adversity was measured via maternal report on at least four occasions at or before age 7 from a single item or psychometrically validated standardized measures.…”

Section: Exposure To Adversitymentioning

confidence: 99%

Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study

Dunn

Soare

Simpkin

et al. 2018

Preprint

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Background: Exposure to "early life" adversity is known to predict DNA methylation (DNAm) patterns that may be related to prolonged psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure.Methods: Using a two-stage structured life course modeling approach (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced greater DNAm changes. We tested this hypothesis in relation to two alternative explanations: an accumulation hypothesis, in which the effect of adversity on DNAm increases with the number of occasions exposed, regardless of timing, and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=670-776). Results:After covariate adjustment and multiple testing correction, we identified 40 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=32) were predicted by the timing of adversity, namely exposures during infancy. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS of lifetime exposure (vs. no exposure) failed to detect these associations.

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Epigenetics and gene expression profile in first-episode psychosis: The role of childhood trauma

Cited by 48 publications

References 69 publications

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

Childhood Trauma in Schizophrenia: Current Findings and Research Perspectives

Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma

Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study

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