scholarly journals Glia-Driven Brain Circuit Refinement Is Altered by Early-Life Adversity: Behavioral Outcomes

2021 ◽  
Vol 15 ◽  
Author(s):  
Katrina A. Milbocker ◽  
Taylor S. Campbell ◽  
Nicholas Collins ◽  
SuHyeong Kim ◽  
Ian F. Smith ◽  
...  
Keyword(s):  
Early Life ◽  
Brain Structures ◽  
Therapeutic Interventions ◽  
Early Life Adversity ◽  
Childhood Experiences ◽  
Clinical Literature ◽  
Brain Circuitry ◽  
History Of ◽  
Brain Circuit ◽  
Synaptic Pruning

Early-life adversity (ELA), often clinically referred to as “adverse childhood experiences (ACE),” is the exposure to stress-inducing events in childhood that can result in poor health outcomes. ELA negatively affects neurodevelopment in children and adolescents resulting in several behavioral deficits and increasing the risk of developing a myriad of neuropsychiatric disorders later in life. The neurobiological mechanisms by which ELA alters neurodevelopment in childhood have been the focus of numerous reviews. However, a comprehensive review of the mechanisms affecting adolescent neurodevelopment (i.e., synaptic pruning and myelination) is lacking. Synaptic pruning and myelination are glia-driven processes that are imperative for brain circuit refinement during the transition from adolescence to adulthood. Failure to optimize brain circuitry between key brain structures involved in learning and memory, such as the hippocampus and prefrontal cortex, leads to the emergence of maladaptive behaviors including increased anxiety or reduced executive function. As such, we review preclinical and clinical literature to explore the immediate and lasting effects of ELA on brain circuit development and refinement. Finally, we describe a number of therapeutic interventions best-suited to support adolescent neurodevelopment in children with a history of ELA.

scholarly journals Blunted stress reactivity reveals vulnerability to early life adversity in young adults with a family history of alcoholism

Addiction ◽  
2018 ◽  
Vol 114 (5) ◽  
pp. 798-806 ◽  
Author(s):  
William R. Lovallo ◽  
Andrew J. Cohoon ◽  
Ashley Acheson ◽  
Kristen H. Sorocco ◽  
Andrea S. Vincent
Keyword(s):  
Young Adults ◽  
Family History ◽  
Early Life ◽  
Stress Reactivity ◽  
Early Life Adversity ◽  
History Of

Inflammatory and Epigenetic Pathways for Perinatal Depression

2015 ◽  
Vol 18 (3) ◽  
pp. 331-343 ◽  
Author(s):  
Lindsey Garfield ◽  
Herbert L. Mathews ◽  
Linda Witek Janusek
Keyword(s):  
Early Life ◽  
Infant Health ◽  
Perinatal Depression ◽  
Life Experiences ◽  
Perinatal Period ◽  
Early Life Adversity ◽  
Targeted Interventions ◽  
Increased Risk ◽  
History Of ◽  
The Impact

Depression during the perinatal period is common and can have adverse consequences for women and their children. Yet, the biobehavioral mechanisms underlying perinatal depression are not known. Adverse early life experiences increase the risk for adult depression. One potential mechanism by which this increased risk occurs is epigenetic embedding of inflammatory pathways. The purpose of this article is to propose a conceptual model that explicates the linkage between early life adversity and the risk for maternal depression. The model posits that early life adversity embeds a proinflammatory epigenetic signature (altered DNA methylation) that predisposes vulnerable women to depression during pregnancy and the postpartum period. As proposed, women with a history of early life adversity are more likely to exhibit higher levels of proinflammatory cytokines and lower levels of oxytocin in response to the demands of pregnancy and new motherhood, both of which are associated with the risk for perinatal depression. The model is designed to guide investigations into the biobehavioral basis for perinatal depression, with emphasis upon the impact of early life adversity. Testing this model will provide a better understanding of maternal depressive risk and improve identification of vulnerable women who would benefit from targeted interventions that can reduce the impact of perinatal depression on maternal–infant health.

Adverse Childhood Experiences, Brain Development, and Mental Health: A Call for Neurocounseling

2018 ◽  
Vol 40 (3) ◽  
pp. 266-278 ◽  
Author(s):  
Carryl P. Navalta ◽  
Lesley McGee ◽  
Jolene Underwood
Keyword(s):  
Mental Health ◽  
Adverse Childhood Experiences ◽  
Brain Structures ◽  
Cumulative Exposure ◽  
Childhood Experiences ◽  
Psychotherapeutic Interventions ◽  
Ace Study ◽  
Adverse Childhood ◽  
Health Related ◽  
History Of

The Adverse Childhood Experiences (ACE) Study provided compelling evidence that abuse, neglect, and other ACEs are the most potent risk factors for the development of health, mental health, and substance use problems. Such negative health-related outcomes parallel the cumulative exposure of the developing brain to the stress response, with resulting impairment in multiple brain structures and functions. Collectively, these sequelae can manifest during childhood, adolescence, or adulthood. We and others have posited that counseling and other psychotherapeutic interventions need to address the individual's multilayered ecology (i.e., biological, psychological, social, cultural/contextual). Neurocounseling can provide a heuristic framework to more effectively assess, conceptualize, and counsel people with a history of ACEs. We provide an update of the clinical neuroscience of ACEs and its implications for counseling, including how contemporary interventions (e.g., mindfulness) can potentially have positive benefits for such individuals.

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 Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions

2017 ◽  
Vol 40 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Brigitte Dahmen ◽  
Vanessa B. Puetz ◽  
Wolfgang Scharke ◽  
Georg G. von Polier ◽  
Beate Herpertz-Dahlmann ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Early Life ◽  
Brain Structures ◽  
Hippocampal Volume ◽  
Granule Cell Layer ◽  
Control Group ◽  
Stress System ◽  
Early Life Adversity ◽  
Diurnal Cortisol ◽  
Hippocampal Subfields

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life.

Childhood trajectories of anxiousness and disruptiveness explain the association between early-life adversity and attempted suicide

2012 ◽  
Vol 42 (11) ◽  
pp. 2373-2382 ◽  
Author(s):  
B. Wanner ◽  
F. Vitaro ◽  
R. E. Tremblay ◽  
G. Turecki
Keyword(s):  
Mental Disorders ◽  
Suicidal Behavior ◽  
Early Life ◽  
Suicide Attempts ◽  
Childhood Adversity ◽  
Externalizing Disorders ◽  
Mediating Effect ◽  
Early Life Adversity ◽  
History Of ◽  
Axis I

BackgroundSuicidal behavior is frequently associated with a history of childhood abuse yet it remains unclear precisely how early life adversity may increase suicide risk later in life. As such, our aim was to examine whether lifetime trajectories of disruptiveness and anxiousness trait dysregulation explain the association between childhood adversity and suicidal behavior; and moreover, to test the potential modifying effects of mental disorders on these associations.MethodA sample of 1776 individuals from a prospective school-based cohort followed longitudinally for over 22 years was investigated. We tested the influence of disruptiveness and anxiousness trajectories from age 6 to 12 years on the association between childhood adversity (i.e. sexual and physical abuse) and history of suicide attempts (SA) using logistic regression models. Both adolescent externalizing and internalizing Axis I disorders and gender were tested as potential modifiers of these associations.ResultsFour distinct longitudinal trajectories were identified for both disruptiveness and anxiousness. The high disruptiveness trajectory accounted for the association between childhood adversity and SA, but only for females. The high anxiousness trajectory also explained the association between adversity and SA; however, in this case it was not sex but mental disorders that influenced the potency of the mediating effect. More specifically, anxiousness fully explained the effect of adversity on SA in the presence of externalizing disorders, whereas in the absence of these disorders, this effect was significantly attenuated.ConclusionsThis study provides evidence that both disruptiveness and anxiousness play an important role in explaining the relationship between childhood adversity and SA.

scholarly journals A Pro-social Pill? The Potential of Pharmacological Treatments to Improve Social Outcomes After Pediatric Traumatic Brain Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Bridgette D. Semple ◽  
Ramesh Raghupathi
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Social Behavior ◽  
Early Life ◽  
Brain Injuries ◽  
Time Window ◽  
Therapeutic Interventions ◽  
Future Research ◽  
Clinical Literature ◽  
The Impact

Traumatic brain injury (TBI) is a leading cause of injury-induced disability in young children worldwide, and social behavior impairments in this population are a significant challenge for affected patients and their families. The protracted trajectory of secondary injury processes triggered by a TBI during early life—alongside ongoing developmental maturation—offers an extended time window when therapeutic interventions may yield functional benefits. This mini-review explores the scarce but promising pre-clinical literature to date demonstrating that social behavior impairments after early life brain injuries can be modified by drug therapies. Compounds that provide broad neuroprotection, such as those targeting neuroinflammation, oxidative stress, axonal injury and/or myelination, may prevent social behavior impairments by reducing secondary neuropathology. Alternatively, targeted treatments that promote affiliative behaviors, exemplified by the neuropeptide oxytocin, may reduce the impact of social dysfunction after pediatric TBI. Complementary literature from other early life neurodevelopmental conditions such as hypoxic ischemic encephalopathy also provides avenues for future research in neurotrauma. Knowledge gaps in this emerging field are highlighted throughout, toward the goal of accelerating translational research to support optimal social functioning after a TBI during early childhood.

scholarly journals On the early-life origins of vulnerability to opioid addiction

2019 ◽  
Author(s):  
Sophia C Levis ◽  
Brandon S Bentzley ◽  
Jenny Molet ◽  
Jessica L Bolton ◽  
Christina R Perrone ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Brain Development ◽  
Early Life ◽  
Opioid Addiction ◽  
Opioid Abuse ◽  
Female Rats ◽  
Early Life Adversity ◽  
History Of ◽  
And Function ◽  
Reward Circuit

AbstractThe origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early-life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA interacts with factors such as increased access to opioids to directly influence brain development and function and cause opioid addiction vulnerability is unknown. We simulated ELA in female rats and this led to a striking opioid addiction-like phenotype. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of a less salient natural reward was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction.

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