scholarly journals Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior

2017 ◽  
Vol 25 ◽  
pp. 145-159 ◽  
Author(s):  
Maya Opendak ◽  
Elizabeth Gould ◽  
Regina Sullivan
2019 ◽  
Author(s):  
Annabel K. Short ◽  
Pamela M. Maras ◽  
Aidan L. Pham ◽  
Autumn S. Ivy ◽  
Tallie Z. Baram

AbstractIn humans, early-life adversity (ELA) is associated with impairments in learning and memory that may emerge later in life. In rodent models, ELA directly impacts hippocampal neuron structure and connectivity with progressive deficits in long-term potentiation and spatial memory function. Previous work has demonstrated that augmented release and actions of the stress-activated neuropeptide, CRH, contribute to the deleterious effects of ELA on hippocampal structure and memory-function. Early-life adversity increases CRH production and levels, and blocking CRH receptor type 1 (CRHR1) within the hippocampus immediately following adversity prevented the memory and LTP problems caused by ELA. Here we queried if blocking CRHR1 during adulthood ameliorates the adverse impact of ELA on memory in middle age. Blocking CRHR1 for a week in two month old male rats prevented ELA-induced deficits in object recognition memory that emerge during middle age. The intervention failed to mitigate the reduction of spatial memory at 4 and 8 months, but restored hippocampus-dependent location memory in ELA-experiencing rats during middle age (12 months of age).Notably, neither ELA nor blocking CRHR1 influenced anxiety- or depression-related behaviors These findings suggest a sensitive period during which interventions can fully prevent long-lasting effects of ELA, yet indicate that interventions later in life offer significant benefits.


Author(s):  
Nine F. Kompier ◽  
Christian Keysers ◽  
Valeria Gazzola ◽  
Paul J. Lucassen ◽  
Harmen J. Krugers

2020 ◽  
Vol 4 (s1) ◽  
pp. 5-5
Author(s):  
Grace Porter ◽  
Juan Morales ◽  
Roslyn Valdespino ◽  
Ashley Acheson ◽  
Jason O’Connor

OBJECTIVES/GOALS: Individuals with a family history of alcoholism (FH+) are more likely to develop an alcohol use disorder than those with no such history. Early life adversity has a high coincidence with FH+ making pathogenic studies difficult in clinical studies. Here, we developed a mouse model to study pathogenic mechanisms underlying these risk factors. METHODS/STUDY POPULATION: Male and female C57BL6/J mice were exposed to increasing concentrations of ethanol (3-21%) or water for 15 days prior to breeding. Ethanol was not present during gestation. Offspring were either removed from the home cage and isolated for 3 hours or left undisturbed from postnatal days 1-21. Beginning on PND 56 offspring mice were assessed for clinically relevant behavioral disruptions in social behavior, cognitive working memory, locomotor activity, anxiety-like phenotypes, ethanol preference and binge drinking behavior. In a separate experiment, brains of Cx3cr2+/GFPxCcr2+/RFP mice from ELA or control conditions were collected every 7 days after birth for assessment of neuroinflammation and central immune cell morphology and density. RESULTS/ANTICIPATED RESULTS: Mice with a family history of ethanol exposure and ELA are predicted to exhibit behavioral changes (impaired working memory, reduced social behavior, increased anxiety-like behaviors, increased ethanol consumption) to a greater extent than mice with a family history of ethanol exposure or ELA alone. We expect markers of neuroinflammation (cytokine expression, immune cell activation) to predict the behavioral changes in these mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol consumption and stressful life events are known environmental precipitants to neuroinflammation, which in turns may predispose individuals to anti-social and risky behavior. A mouse model of these early postnatal conditions will allow basic scientists to unravel the biological underpinnings of the behaviors driven by these factors.


2018 ◽  
Author(s):  
Erin C. Dunn ◽  
Thomas W. Soare ◽  
Andrew J. Simpkin ◽  
Matthew J. Suderman ◽  
Yiwen Zhu ◽  
...  

AbstractBackgroundExposure 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.MethodsUsing 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).ResultsAfter 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.ConclusionsThe developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Infancy appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed vs. unexposed to “early life” adversity may dilute observed effects.


2019 ◽  
Author(s):  
Mary Elizabeth Zinn ◽  
Edward Huntley ◽  
Daniel Keating

Introduction. Early life adversity (ELA) can result in negative health-outcomes, including psychopathology. Evidence suggests that adolescence is a critical developmental period for processing ELA. Identity formation, which is crucial to this developmental period, may moderate the effect between ELA and psychopathology. One potential moderating variable associated with identity formation is Prospective Self, a latent construct comprised of future-oriented attitudes and behaviors.Methods. Participants are from the first wave of an ongoing longitudinal study designed to characterize behavioral and cognitive correlates of risk behavior trajectories. A community sample of 10th and 12th grade adolescents (N = 2017, 55% female) were recruited from nine public school districts across eight Southeastern Michigan counties in the United States. Data were collected in schools during school hours or after school via self-report, computer-administered surveys. Structural equation modeling was used in the present study to assess Prospective Self as a latent construct and to evaluate the relationship between ELA, psychopathology, and Prospective Self.Results. Preliminary findings indicated a satisfactory fit for the construct Prospective Self. The predicted negative associations between Prospective Self and psychopathology were found and evidence of moderation was observed for externalizing behavior problems, such that the effects of ELA were lower for individuals with higher levels of Prospective Self. Conclusion. These results support the role of Prospective Self in conferring resilience against externalizing behavior problems associated with ELA among adolescents. Keywords: Adolescence, Adverse Childhood Experiences, Psychopathology, Self-concept, Adolescent Health, Early Life Adversity


Author(s):  
Meg Dennison ◽  
Katie McLaughlin

Early-life adversity is associated with elevated risk for a wide range of mental disorders across the lifespan, including those that involve disruptions in positive emotionality. Although extensive research has evaluated heightened negative emotionality and threat processing as developmental mechanisms linking early-life adversity with mental health problems, emerging evidence suggests that positive emotions play an integral, but complex, role in the association of early-life adversity with psychopathology. This chapter identifies two pathways through which positive emotion influences risk for psychopathology following early-life adversity. First, experiences of early-life adversity may alter the development of the “positive valence system”, which in turn increases risk for psychopathology. Second, the association between adversity and psychopathology may vary as a function of individual differences in positive emotionality. We consider how the development of positive emotionality—measured at psychological, behavioral and neurobiological levels—may be altered by early-life adversity, creating a diathesis for psychopathology. We additionally review evidence for the role of positive emotion, measured at multiple levels, as a protective factor that buffers against the adverse impacts of adversity. In integrating these two roles, it is proposed that characteristics of environmental adversity, including developmental timing, duration, and type of adversity, may differentially impact the development of positive emotionality, leading to a better understanding of risks associated with specific adverse experiences. Methodological issues regarding the measurement of adverse environments as well as implications for early intervention and treatment are discussed.


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