Longitudinal changes in amygdala, hippocampus and cortisol development following early caregiving adversity

Decades of research have shown long-term effects of early caregiving adversity on stress physiology and limbic brain regions, two key biological systems that are implicated in risk for internalizing disorders. Although stress physiology and limbic brain structure undergo significant maturational change during childhood and adolescence, and reciprocally influence each other, the effects of early caregiving adversity on these developmental processes is not well understood. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4-20 years old) completed 1-3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239, providing a total of 380 diurnal datasets), structural MRI (N = 156, providing a total of 306 scans) and parent-reported internalizing symptoms (N = 133, providing a total of 227 time points). We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth of the amygdala, resulting in smaller volumes by adolescence. Results also suggested feed-forward brain-to-hormone mechanisms, such that both amygdala and hippocampal volumes were prospectively associated with morning cortisol levels two years later. Finally, amygdala and hippocampal volumes were independently associated with internalizing scores across the entire sample. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood

The impact of childhood deprivation on adult neuropsychological functioning is associated with ADHD symptom persistence

Background: Institutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment – the large scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s – we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation-related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).Methods: Adult neuropsychological functioning was assessed across five domains (inhibitory control, facial emotion recognition, decision-making, prospective memory and IQ) in 70 previously-institutionalized adoptees (mean age= 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age= 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires.Results: Early institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotionrecognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory.Conclusions: These results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair neuropsychological functioning across the lifespan – effects that are linked specifically to deprivation-related adult ADHD symptoms

Early deprivation alters structural brain development from middle childhood to adolescence

Hypotheses concerning the biologic embedding of early adversity via developmental neuroplasticity mechanisms have been proposed on the basis of experimental studies in animals. However, no studies have demonstrated a causal link between early adversity and neural development in humans. Here, we present evidence from a randomized controlled trial linking psychosocial deprivation in early childhood to changes in cortical development from childhood to adolescence using longitudinal data from the Bucharest Early Intervention Project. Changes in cortical structure due to randomization to foster care were most pronounced in the lateral and medial prefrontal cortex and in white matter tracts connecting the prefrontal and parietal cortex. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the importance of early placement into family-based care to mitigate lasting neurodevelopmental consequences associated with early-life deprivation

Environmental conditions to promote healthy childhood brain/behavioral development: Informing early preventive interventions for delivery in routine care

Environmental experiences early in life have strong and enduring consequences for cognitive, emotional, and neurobiological development and related physical and mental health trajectories. The powerful influence of early caregiver nurturance and stimulation on promoting positive neurodevelopmental outcomes has been demonstrated across species. These findings elucidate the environmental conditions known to facilitate healthy neurodevelopment and underscore the potential for modifiable psychosocial factors in the environment to be harnessed to inform early preventive interventions to promote health and adaptive development. A framework for early preventive interventions to enhance nurturing and responsive caregiving for implementation during early sensitive periods of brain development delivered within existing health or educational infrastructures is proposed. Emotional development during sensitive periods is an important, under-recognized, and abundantly modifiable predictor of mental and physical health outcomes that warrants investment of resources and integration of interventions into public health infrastructure for children worldwide. Future studies are needed to further clarify whether and when sensitive periods are present for key developmental domains to inform the optimal timing and targets of these interventions. Numerous available empirically supported early interventions may be modified and applied in briefer and more feasible modalities of delivery to broader populations of developing children. As well established in growth and development across species, essential environmental inputs that are particularly important at specified developmental periods facilitate optimal growth trajectories. Such principles hold great potential in application to early child neurodevelopment to facilitate a thriving and resilient human population

The Impact of Childhood Maltreatment: A Review of Neurobiological and Genetic Factors

Childhood maltreatment represents a significant risk factor for psychopathology. Recent research has begun to examine both the functional and structural neurobiological correlates of adverse care-giving experiences, including maltreatment, and how these might impact on a child’s psychological and emotional development. The relationship between such experiences and risk for psychopathology has been shown to vary as a function of genetic factors. In this review we begin by providing a brief overview of neuroendocrine findings, which indicate an association between maltreatment and atypical development of the hypothalamic–pituitary–adrenal axis stress response, which may predispose to psychiatric vulnerability in adulthood. We then selectively review the magnetic resonance imaging (MRI) studies that have investigated possible structural and functional brain differences in children and adults who have experienced childhood maltreatment. Differences in the corpus callosum identified by structural MRI have now been reliably reported in children who have experienced abuse, while differences in the hippocampus have been reported in adults with childhood histories of maltreatment. In addition, there is preliminary evidence from functional MRI studies of adults who have experienced childhood maltreatment of amygdala hyperactivity and atypical activation of frontal regions. These functional differences can be partly understood in the context of the information biases observed in event-related potential and behavioral studies of physically abused children. Finally we consider research that has indicated that the effect of environmental adversity may be moderated by genotype, reviewing pertinent studies pointing to gene by environment interactions. We conclude by exploring the extent to which the growing evidence base in relation to neurobiological and genetic research may be relevant to clinical practice and intervention

Amygdala connectivity at rest following two forms of early life stress

University of Minnesota Ph.D. dissertation. June 2017. Major: Child Psychology. Advisor: Kathleen Thomas. 1 computer file (PDF); v, 99 pages.Early life stress (ELS), including experiences of abuse and neglect, poses a threat to the typical trajectory of development, and is associated with altered emotion processing and regulation. The neural structures underlying emotion processing and regulation, the amygdala and prefrontal cortex (PFC), show both structural and functional differences following early life stress. However, there is little understanding of how baseline intrinsic connectivity between the amygdala and PFC is impacted by ELS. Resting state amygdala connectivity was explored in two samples who had experienced ELS. Study 1 included youth who had experienced institutional rearing, an extreme form of deprivation. Post-institutionalized youth showed increased amygdala-PFC connectivity and decreased amygdala-insula connectivity in comparison to non-adopted peers. Study 2 explored connectivity in adults with a history of childhood maltreatment. Altered amygdala connectivity was observed in relation to the type and timing of maltreatment. Additionally, an interaction between maltreatment history and self-reported resilience was observed in amygdala-caudate connectivity. Both studies provided evidence of disrupted amygdala resting-state connectivity in association with ELS. Results suggest that in addition to amygdala-PFC circuitry, amygdala connectivity with other regions of the brain is sensitive to ELS

The Relationship Between Child Adversity, Anxiety Symptoms and White Matter Integrity

Chronic activation of the stress response during childhood has been proposed to cause long-term maladaptive changes to the structure of stress response systems, resulting in chronic mental illness. This study helps us to understand how maltreatment in children is associated with differences in white matter integrity and how these factors relate to anxiety symptoms in children. Using Diffusional Kurtosis Imaging data, we examined 106 participants, aged 7-16. Approximately half of the participants were recruited through the Department for Children and Families, and had experienced at least one out-of-home placement following a verified instance of abuse or neglect. Associations between white matter integrity, environmental stressors, and anxiety symptoms were assessed. This study found that specific anxiety symptoms associated with Post-Traumatic Stress Disorder were associated with FA reductions. In addition, levels of general adversity and intrafamilial violence were both associated with Fractional Anisotropy reductions. Understanding the mechanisms by which early adversity is linked to long-term psychiatric outcomes is the first step in designing interventions for this vulnerable population

Early-life adversity and neurological disease: age-old questions and novel answers.

Neurological illnesses, including cognitive impairment, memory decline and dementia, affect over 50 million people worldwide, imposing a substantial burden on individuals and society. These disorders arise from a combination of genetic, environmental and experiential factors, with the latter two factors having the greatest impact during sensitive periods in development. In this Review, we focus on the contribution of adverse early-life experiences to aberrant brain maturation, which might underlie vulnerability to cognitive brain disorders. Specifically, we draw on recent robust discoveries from diverse disciplines, encompassing human studies and experimental models. These discoveries suggest that early-life adversity, especially in the perinatal period, influences the maturation of brain circuits involved in cognition. Importantly, new findings suggest that fragmented and unpredictable environmental and parental signals comprise a novel potent type of adversity, which contributes to subsequent vulnerabilities to cognitive illnesses via mechanisms involving disordered maturation of brain 'wiring'

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted