CONTEMPORARY APPROACHES TO STUDYING EARLY LIFE STRESS AND THE DEVELOPING BRAIN

Chairs & Presenters:

Kathryn Humphreys 
Tracy Riggins (Co-chair)
Morgan Botdorf (Co-chair)
Jamie Hanson
Emilio Valadez

Details of Research Subjects: Neurodevelopment and Plasticity including imaging work, Stress, Adversity

Ages of Research Subjects: prenatal, infancy, adolescence

Topics: Neurodevelopment and Plasticity including imaging work, Stress, Adversity

Description:

It is well understood that early adversity negatively impacts developing brain architecture. This symposium brings together research pushing the boundaries of this field by examining the impact of early adversity on the brain in more nuanced and exciting ways. The first talk will present data assessing the impacts of early adversity during both the pre- and postnatal period on the structure of the hippocampus, a stress sensitive brain region. The second talk will present data showing that early stress physiology relates to functional connectivity of the hippocampus later in development. This talk will also probe the question of how more typical variations in early stressful life events impact functional development of the hippocampus. The third talk will present data from a large sample of children showing that differences in BOLD signal variability of reward processing regions mediate the association between early adversity, specifically family conflict, and depression. The fourth talk will present data showing that a parenting intervention may be effective in limiting the impact of early adversity on functional development of regions important for emotion regulation. This symposium will be of interest to a wide audience as it includes a diverse group of researchers in the field who address this question across developmental periods ranging from the prenatal period through adolescence. We will promote discussion by presenting new data addressing the long-time question of how experience gets under the skin and shapes development along with mechanisms that hold potential for decreasing the impact of early adversity on the brain.

PRESENTATIONS:

STRESS AND HIPPOCAMPAL VOLUME: INVESTIGATING THE POTENTIAL FOR SENSITIVE PERIODS

Kathryn L. Humphreys, Ph.D. (Primary presenter), Vanderbilt University, Nashville, TN

The human brain undergoes rapid change in the first years of life. Stress-sensitive regions may be particularly vulnerable to threatening experiences that occur during periods of development. We provide evidence of the potential for early life (birth through age 5 years) as a period when the hippocampus may be particularly sensitive to stress. In 178 early adolescents (M=11.39, SD=1.04 years; 43% male) interviewed regarding stress exposure and who also completed an anatomical MRI scan, we found a moderate and significant negative association between stress severity during early childhood and bilateral hippocampal volume. Stress severity in older childhood was not associated with differences in hippocampal volume. We followed this work by investigating the stress experienced prenatally in relation to newborn hippocampal volume. Data collection is ongoing, and to date 42 infants (M=4.79, SD=0.88 weeks; 44% male) have completed anatomical scans. Women were interviewed in pregnancy to obtain assessments of preconception and prenatal stress exposure. Taken together, this work informs the potential for sensitive periods in key points in hippocampal development that align with increased brain plasticity.

DO ‚ATYPICAL‚ VARIATIONS IN STRESSFUL LIFE EVENTS AND STRESS PHYSIOLOGY IMPACT HIPPOCAMPAL FUNCTIONAL CONNECTIVITY IN YOUNG CHILDREN?

Morgan Botdorf (Co-chair, primary presenter), Lea Dougherty, & Tracy Riggins (Co-chair)

Department of Psychology, University of Maryland, College Park, MD

Much work has highlighted the impacts of extreme early life stress (i.e., abuse, neglect, maltreatment) on the developing brain, especially on stress sensitive regions like the hippocampus. However, it is relatively unknown whether more typical variations in stressful life events (e.g., parental divorce, changing schools) might affect hippocampal development through similar mechanisms. In this talk, we will discuss how variations in stressful events and early stress physiology (i.e., cortisol levels) relate to functional development of the hippocampus in children. We will do this using two longitudinal datasets of children ranging from preschool age to middle childhood. First, we will present data from a sample of over-recruited children at risk for depression due to parental depression history. These data show that individual differences in early (3-5 years), but not concurrent (5-9 years), stress physiology (cortisol) are related to differences in functional connectivity between the hippocampus and both midcingulate cortex and precuneus. Second, we will present data from a sample of 200 typically developing 4- to 8-year-old children assessing how typical variations in stressful life events relates to hippocampal functional connectivity. Data for this study has been collected and preprocessed. Analyses are ongoing and are focused on investigating how stressful life events relate to initial functional connectivity and changes in functional connectivity over a two year period. Together, results of these studies will shed light on whether more typical variations in stressful life events impact functional development of hippocampus during early childhood, an important period of brain development.

FMRI SIGNAL VARIABILITY IN REWARD NEURAL HUBS RELATE TO EARLY-LIFE ADVERSITY AND SYMPTOMS OF DEPRESSION

Jamie L. Hanson, University of Pittsburgh, Pittsburgh, PA

Those who suffer early-life adversity (e.g., exposure to abuse or violence) are at a heightened risk for affective disorders later in life, particularly depression. Though well-studied in psychological and epidemiological research, the exact neurobiological mechanisms mediating these associations remain unclear. Emerging evidence, however, implicates dysfunction of reward-related neural circuitry in the pathophysiology of depression. Connected to these ideas, here we investigate a novel biomarker to more robustly understand connections between adversity, depression, and neurobiology. Specifically, BOLD fMRI signal variability may be an important individual difference measure of interest, often demonstrating more predictive power than mean activation patterns. Such temporal variability may reflect differences in neuronal signal detection, dynamic range, or the ability to move into different network states. Leveraging a large-scale neuroimaging dataset of 9-10-year-old participants (n=11,875), we found that early-life adversity, in the form of high family conflict, was: 1) related to higher symptoms of depression; 2) associated with greater variability in a key reward-related neural hub, the ventral striatum, on a reward-processing fMRI task, and 3) VS BOLD variability mediated associations between family conflict and depression (indirect effect [a X b], z=1.992, p=.046). In contrast, mean BOLD activity for similar fMRI contrasts did not relate to depression or adversity. This novel work affords an opportunity to identify critical neurobiological alterations related to mood dysregulation and connected to adversity, elucidating novel markers of depression risk. Sustained progress on this issue could produce insights that practitioners could eventually use in reducing the negative mental health consequences of different early-life adversities.

EARLY PARENTING INTERVENTION EFFECTS ON AT-RISK CHILDREN’S NEURAL REACTIVITY TO FACES

Emilio A. Valadez1 (Primary Presenter), Nim Tottenham2, Alexandra R. Tabachnick1, Daniel S. Pine3, & Mary Dozier1

1Department of Psychological and Brain Sciences, University of Delaware

2Department of Psychology, Columbia University

3Section on Development and Affective Neuroscience, National Institute of Mental Health 

Early adversity is associated with atypical neurodevelopment and heightened reactivity to potential threat. The present study aimed to test the causal impact of an early parenting intervention (Attachment and Biobehavioral Catch-up; ABC) on children’s neural processing of threatening faces in a longitudinal randomized clinical trial. Participants (N = 60, Mage = 10.0 years) included 41 high-risk children whose parents were randomized to receive either ABC (n = 21) or a control intervention (n = 20) while children were infants, in addition to a comparison sample of low-risk children (n = 19). Children viewed pictures of fearful and neutral faces during functional magnetic resonance imaging. Across both types of faces, high-risk children exhibited greater occipital cortex and fusiform gyrus activation than low risk-children, suggesting greater orienting to potential threat. Additionally, children in the ABC group had greater face-related activation than children in the control intervention group in clusters of brain regions including the right orbitofrontal cortex, right insula, and bilateral anterior cingulate cortex – brain regions commonly associated with emotion regulation. There were no group differences in a fearful minus neutral contrast; however, in light of previous findings that maltreated children tend to perceive even neutral faces as more threatening than non-maltreated children, results suggest that early parenting intervention (in this case, ABC) enhances at-risk children’s emotion regulation in the face of potential threat.