Adverse Childhood Experiences Run Deep: Toxic Early Life Stress, Telomeres, and Mitochondrial DNA Copy Number, the Biological Markers of Cumulative Stress

BioEssays ◽  
2018 ◽  
Vol 40 (9) ◽  
pp. 1800077 ◽  
Author(s):  
Kathryn K. Ridout ◽  
Mariam Khan ◽  
Samuel J. Ridout
Keyword(s):  
Mitochondrial Dna ◽  
Adverse Childhood Experiences ◽  
Life Stress ◽  
Early Life ◽  
Copy Number ◽  
Early Life Stress ◽  
Childhood Experiences ◽  
Cumulative Stress ◽  
Mitochondrial Dna Copy Number ◽  
Adverse Childhood

scholarly journals Early Life Stress Promotes Heroin Seeking But Does Not Alter the Excitability of Insular Pyramidal Cells Targeting the Nucleus Accumbens

2021 ◽  
Vol 15 ◽  
Author(s):  
Jonna M. Leyrer-Jackson ◽  
Paula F. Overby ◽  
Erin K. Nagy ◽  
M. Foster Olive
Keyword(s):  
Nucleus Accumbens ◽  
Adverse Childhood Experiences ◽  
Life Stress ◽  
Early Life ◽  
Pyramidal Neurons ◽  
Early Life Stress ◽  
Self Administration ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Seeking Behavior

A number of retrospective studies have demonstrated adverse childhood experiences are associated with increased vulnerability to substance use disorders, including opioid use disorders (OUDs). These adverse childhood experiences, also referred to as early life stress (ELS), can be modeled in laboratory animals by various paradigms including limited bedding and nesting (LBN) procedures. Studies using rodent models of ELS have been shown to recapitulate various aspects of OUDs, including relapse propensity and perseverance of drug-seeking behavior. In the current study, we utilized the LBN paradigm to explore potential effects on heroin self-administration, extinction, and relapse-like behaviors in male and female rats. We also utilized in vitro whole-cell electrophysiology to examine the effects of LBN and repeated heroin administration on the excitability of pyramidal neurons in the anterior insular cortex (AIC) projecting to the nucleus accumbens core (NAc), as recent studies suggest that this circuit may mediate various aspects of OUDs and may be compromised as a result of either ELS or OUDs. We observed that compared to control animals, rats exposed to LBN conditions during postnatal days 2–9 showed increased breakpoints for heroin self-administration under a progressive ratio schedule of reinforcement, impaired extinction of heroin-seeking behavior, and increased reinstatement of heroin-seeking behavior induced by heroin-associated cues. No effect of LBN rearing conditions were observed on the acquisition and maintenance of heroin self-administration, and no sex differences in heroin intake were observed. LBN and control reared animals showed no differences in the excitability of AIC-NAc pyramidal neurons, but animals treated with repeated heroin showed decreased excitability of these neurons through a significant increase in rheobase and reduction in action potentials induced by depolarizing currents. Together, these results suggest that ELS exposure produces exacerbations of heroin seeking behavior without parallel effects on AIC-NAc excitability, although heroin itself reduces the excitability of these neurons.

scholarly journals Early life stress during the neonatal period alters social play and Line1 during the juvenile stage of development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Amelia Cuarenta ◽  
Stacey L. Kigar ◽  
Ian C. Henion ◽  
Liza Chang ◽  
Vaishali P. Bakshi ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Copy Number ◽  
Neonatal Period ◽  
Early Life Stress ◽  
Social Play ◽  
Psychological Disorders ◽  
Dna Copy Number ◽  
Juvenile Period ◽  
Stage Of Development

AbstractEarly life stress (ELS) has been shown to have a significant impact on typical brain development and the manifestation of psychological disorders through epigenetic modifications that alter gene expression. Line1, a retrotransposon associated with genetic diversity, has been linked with various psychological disorders that are associated with ELS. Our previous work demonstrated altered Line1 DNA copy number in the neonatal period following stressful experiences; we therefore chose to investigate whether early life stress altered Line1 retrotransposition persists into the juvenile period of development. Our study uses a neonatal predator odor exposure (POE) paradigm to model ELS in rats. We examined Line1 using qPCR to assess Line1 expression levels and DNA copy number in the male and female juvenile amygdala, hippocampus and prefrontal cortex—areas chosen for their association with affective disorders and stress. We report a sex difference in Line1 levels within the juvenile amygdala. We also find that ELS significantly increases Line1 DNA copy number within the juvenile amygdala which correlates with reduced juvenile social play levels, suggesting the possibility that Line1 may influence juvenile social development.

scholarly journals Adverse childhood experiences and early life inflammation in the Avon longitudinal study of parents and children

2020 ◽  
Vol 122 ◽  
pp. 104914
Author(s):  
Rebecca E Lacey ◽  
Mel Bartley ◽  
Michelle Kelly-Irving ◽  
Leonardo Bevilacqua ◽  
Eleonora Iob ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Childhood Experiences ◽  
Parents And Children ◽  
Adverse Childhood ◽  
Avon Longitudinal Study

scholarly journals An exploration of addiction in adults experiencing early-life stress: a metasynthesis

2017 ◽  
Vol 25 (0) ◽  
Author(s):  
Carla Araujo Bastos Teixeira ◽  
Gerri Lasiuk ◽  
Sylvia Barton ◽  
Maria Neyrian de Fatima Fernandes ◽  
Edilaine Cristina da Silva Gherardi-Donato
Keyword(s):  
Qualitative Research ◽  
Life Stress ◽  
Early Life ◽  
Critical Appraisal ◽  
Early Life Stress ◽  
Specific Area ◽  
Childhood Experiences ◽  
Research Findings ◽  
Childhood Violence ◽  
Critical Appraisal Skills

ABSTRACT Objective: to review and synthesize qualitative research on the links between early-life stress and addiction behaviours in adulthood. Method: metasynthesis to review qualitative research findings based on procedures that outline how to identify themes or constructs across studies in a specific area. Comprehensive searches of multiple electronic databases were performed. The initial search yielded 1050 articles and the titles and abstracts were screened for inclusion based on predetermined criteria. Thirty-eight full text, peer-reviewed articles were retrieved and assessed by three independent reviewers. Twelve articles were eligible for full review and appraised using the Critical Appraisal Skills Programme (CASP) tools. Results: the findings revealed that clear associations exist between early-life stress and addictive behaviours in adulthood, such as between trauma in childhood, violence, and addictive behaviours. A common theme in the findings indicates that participants turn to addictive substances as a way of strategically coping with stressful childhood experiences, regardless of the harmful side effects or detrimental social outcomes. Conclusion: it can be inferred that addiction may be viewed as a way to deal with adversity in childhood and that there is an interrelationship between addiction, domestic violence and crime.

scholarly journals Adverse childhood experiences and asthma: trajectories in a national cohort

Thorax ◽  
2021 ◽  
Vol 76 (6) ◽  
pp. 547-553
Author(s):  
Kathrine Pape ◽  
Whitney Cowell ◽  
Camilla Sandal Sejbaek ◽  
Niklas Worm Andersson ◽  
Cecilie Svanes ◽  
...  
Keyword(s):  
Childhood Asthma ◽  
Early Onset ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Late Onset ◽  
Multinomial Logistic Regression ◽  
Study Cohort ◽  
Childhood Experiences ◽  
Asthma Phenotypes ◽  
Adverse Childhood

ObjectiveResearch has linked early adverse childhood experiences (ACEs) with asthma development; however, existing studies have generally relied on parent report of exposure and outcome. We aimed to examine the association of early life ACEs with empirically determined trajectories of childhood asthma risk, using independent register information on both exposures and outcome.MethodsBased on nationwide registries, we established a study cohort of 466 556 children born in Denmark (1997–2004). We obtained information on ACEs during the first 2 years of life (bereavement, parental chronic somatic and/or mental illness) and childhood asthma diagnosis or medication use from birth through age 10 years from the Danish National Patient and Prescription Registries, respectively. We identified asthma phenotypes using group-based trajectory modelling. We then used multinomial logistic regression to examine the association between early ACEs and asthma phenotypes.ResultsWe identified four asthma phenotypes: non-asthmatic, early-onset transient, early-onset persistent and late-onset asthma. Girls with early-onset transient asthma (OR 1.13, 95% CI 1.04 to 1.24), early-onset persistent asthma (1.27, 95% CI 1.08 to 1.48) or late-onset asthma (OR 1.28, 95% CI 1.11 to 1.48) vs no asthma were more likely to have early life ACE exposure compared with girls without ACE exposure. Results were similar for boys who also had experienced early life ACEs with ORs of 1.16 (95% CI 1.08 to 1.25), 1.34 (95% CI 1.20 to 1.51) and 1.11 (95% CI 0.98 to 1.25), respectively.ConclusionIn a nationwide-population study, we identified three childhood onset asthma phenotypes and found that ACEs early in life were associated with increased odds for each of these asthma phenotypes among both girls and boys.

scholarly journals Adverse childhood experiences (ACEs) associated with reduced cognitive flexibility in both college and community samples

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260822
Author(s):  
Vrinda Kalia ◽  
Katherine Knauft ◽  
Niki Hayatbini
Keyword(s):  
College Students ◽  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Cognitive Flexibility ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Wisconsin Card Sorting Test ◽  
Early Life Adversity ◽  
Childhood Experiences ◽  
Adverse Childhood

The prefrontal cortex is sensitive to stress experiences and significantly impacted by early life adversity. Cognitive flexibility is an executive function that is associated with positive outcomes in adulthood and implicated in activity in the prefrontal cortex. The relationship between early life adversity and cognitive flexibility is underreported. Using the cumulative risk model, we conducted two studies to examine the association between early life adversity and cognitive flexibility in college students and adults (cumulative N = 510). Exposure to early life adversity was assessed using the adverse childhood experiences scale (ACEs). Cognitive flexibility was assessed using the Wisconsin Card Sorting Test (WCST). Additionally, as perceived chronic stress is associated with impaired prefrontal cortex function, we measured that as well. Higher number of ACEs was correlated with lower number of completed categories on the WCST in both college students and adults. Perceived chronic stress was not associated with cognitive flexibility, but did correlate positively with ACEs. Individuals with a higher number of ACEs were also more likely to report higher levels of perceived chronic stress. Hierarchical regression analyses indicated that exposure to adverse childhood experiences predicted lower scores on completed categories. Our findings provide further evidence that individuals with early life adversity exhibit reduced cognitive flexibility in adulthood.

It doesn’t end there: Mental health difficulties across ages 3-14 mediate the long-term association between early-life adversity and poorer cognitive functioning

2020 ◽  
Author(s):  
Tochukwu Nweze ◽  
Amy Orben ◽  
Anne-Laura Van Harmelen ◽  
Delia Fuhrmann ◽  
Rogier Kievit
Keyword(s):  
Mental Health ◽  
Working Memory ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Memory Task ◽  
Poor Mental Health ◽  
Cognitive Outcomes ◽  
Early Life Adversity ◽  
Childhood Experiences ◽  
Adverse Childhood

SummaryBackground: Early-life adversity is associated with adverse mental health outcomes and poorer cognitive functioning in later development. However, little is known about how early-life adversity, mental health and cognition affect one another or how the effects unfold over time. In a unique longitudinal sample, we use a path model approach to study whether poorer mental health in childhood may mediate the effects of early-life adversity on later cognitive outcomes.Methods: We used 5-wave longitudinal data from the Millennium Cohort Study, a British population study that prospectively sampled children born between September 1, 2000 and January 11, 2002. We used data collected when the children were aged 3, 5, 7, 11 and 14. Information on exposure to adverse childhood experiences and mental health were provided by parents, while the children completed two cognitive tasks and additional mental health questionnaires at ages 11 and 14. A global adversity score was extracted from multiple adverse childhood experiences collected in the study using Principal Component Analysis. Total errors in a working memory task and total correct number of words in a vocabulary task were the principal cognitive outcomes. Total scores on the Strengths and Difficulties Questionnaire were modeled as mediators.Findings: The sample consisted of 13,287 children (Male = 6,712, Female = 6,575) who completed the working memory task at age 11 and 11,726 children (Male = 5,884, Female = 5,842) who completed a vocabulary task at age 14. We found a significant total association between global adversity and poorer performance on working memory (β = 0.116, p < 0.001 [95%CI 0.098, 0.134]) and vocabulary scores (β = -0.112, p < 0.001, [95% CI-0.130, -0.094]) tasks. Notably, current and previous mental health mediated a substantial proportion (working memory: 59%; vocabulary: ¬65%), of these effects. Our analysis showed that adversity has an enduring adverse effect on mental health, and that poorer mental health is associated with poorer cognitive performance later on in development. Moreover, the adverse effects of mental health were cumulative: poor mental health early on is associated with poorer cognitive scores up to 11 years later, above and beyond contemporaneous mental health.Interpretations: Children who experience early-life adversity are more likely to suffer from poorer mental health, which in turn is associated with poorer cognitive performance in adolescence. Our findings highlight at least one potential mechanism through which early-life adversity leads to poorer cognitive outcomes: Prolonged periods of poor mental health may have lasting, partially cumulative effects on working memory and vocabulary. These findings have important potential clinical and educational implications, because they suggest that academic and cognitive resilience may be supported through early mental health interventions in vulnerable children. Funding: TN is supported by the Cambridge Trust (University of Cambridge). ALVH is supported by Royal Society, and the Social Safety and Resilience programme at Leiden University. RAK was supported by Rogier A. Kievit, Medical Research Council (http://dx.doi.org/10.13039/501100000265), Award ID: SUAG/047 G101400 and a Hypatia Fellowship (Radboud University).

scholarly journals Adverse Childhood Experiences Associated with Greater Internalization of Weight Stigma in Women with Excess Weight

Obesities ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 49-57
Author(s):  
Natalie G. Keirns ◽  
Cindy E. Tsotsoros ◽  
Samantha Addante ◽  
Harley M. Layman ◽  
Jaimie Arona Krems ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Weight Stigma ◽  
Adult Women ◽  
Childhood Experiences ◽  
Household Dysfunction ◽  
Adverse Childhood ◽  
Early Life Factor ◽  
Life Factor

Adverse childhood experiences (ACEs) may be an early life factor associated with adult weight stigma via biological (e.g., stress response), cognitive (e.g., self-criticism/deprecation), and/or emotional (e.g., shame) mechanisms. This pilot study investigated relationships between ACEs and internalized and experienced weight stigma in adult women with overweight/obesity and explored differential relationships between weight stigma and ACE subtypes (i.e., abuse, neglect, household dysfunction). Adult women (68% white, Mage = 33 ± 10 years, MBMI = 33.7 ± 7.2 kg/m2) completed measures of ACEs (ACE Questionnaire), internalized weight stigma (IWS; Weight Bias Internalization Scale—Modified; WBIS—M), and lifetime experiences of weight stigma (yes/no). Data were analyzed with linear and logistic regression (n = 46), adjusting for age, race, and body mass index (BMI). Linear regressions revealed a positive association between ACE and WBIS—M scores (β = 0.40, p = 0.006), which was driven by Abuse-type ACEs (β = 0.48, p = 0.009). Relationships between WBIS—M scores and Neglect- and Household-Dysfunction-type ACEs did not reach significance (β = 0.20, p = 0.173; β = −0.16, p = 0.273). Though descriptive statistics revealed greater rates of experienced weight stigma endorsement by those with high-3+ ACEs (81%) vs. medium-1–2 ACEs (67%) or low/no-0 ACEs (60%), ACE scores were not significantly associated with experienced weight stigma in logistic regression (Wald = 1.36, p = 0.244, OR = 1.324, 95%, CI = 0.825–2.125). ACEs may be an early life factor that increase the risk for internalizing weight stigma in adulthood. Larger studies should confirm this relationship and follow-up on descriptive findings suggesting a potential association between ACEs and experienced weight stigma.

scholarly journals How do early-life adverse childhood experiences mediate the relationship between childhood socioeconomic conditions and adolescent health outcomes in the UK?

2020 ◽  
pp. jech-2020-213817
Author(s):  
Viviane S Straatmann ◽  
Eric Lai ◽  
Catherine Law ◽  
Margaret Whitehead ◽  
Katrine Strandberg-Larsen ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Adverse Childhood Experiences ◽  
Early Life ◽  
Behavioural Problems ◽  
Cognitive Disability ◽  
Socioeconomic Conditions ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
The Uk ◽  
The Relationship

BackgroundBoth adverse childhood experiences (ACEs) and adverse childhood socioeconomic conditions (SECs) in early life are associated with poor outcomes across the life course. However, the complex interrelationships between childhood SECs and ACEs are unclear, as are the consequences for health outcomes beyond childhood. We therefore assessed the extent to which early-life ACEs mediate the relationship between SECs and socioemotional behavioural problems, cognitive disability and overweight/obesity in adolescence.MethodsWe used longitudinal data from the UK Millennium Cohort Study (MSC). Outcomes assessed at age 14 were socioemotional behavioural problems, cognitive disability and overweight/obesity. SECs at birth were measured by maternal education. Potentially mediating ACEs measured up to 5 years were verbal and physical maltreatment, parental drug use, domestic violence, parental divorce, maternal mental illness and high frequency of parental alcohol use. We used counterfactual mediation analysis to assess the extent to which ACEs mediate the association between SECs at birth and behavioural, cognitive and physical outcomes at age 14, estimating total (TE), natural direct and indirect effects, and mediated proportions.ResultsChildren with disadvantaged SECs were more likely to have socioemotional behavioural problems (relative risk (RR) 3.85, 95% CI 2.48 to 5.97), cognitive disability (RR 3.87, 95% CI 2.33 to 6.43) and overweight/obesity (RR 1.61, 95% CI 1.32 to 1.95), compared to those with more advantaged SECs. Overall, 18% of the TE of SECs on socioemotional behavioural problems was mediated through all ACEs investigated. For cognitive disability and overweight/obese, the proportions mediated were 13% and 19%, respectively.ConclusionACEs measured up to age 5 years in the MCS explained about one-sixth of inequalities in adolescents behavioural, cognitive and physical outcomes.

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