Prefrontal Cortex Structure Shaped by Early Institutionalization is Associated with Externalizing Psychopathology and Cognitive Capacity

• In Event: Biobehavioral Developmental Mechanisms Linking Early Institutional Care to Later Externalizing Psychopathology

Abstract

Experimental studies in animals have provided evidence of biological embedding of early adversity via developmental neuroplasticity mechanisms (Francis et al., 1999, 2002). Rodent studies have demonstrated that experimental manipulation of postnatal experience leads to differences in neural development which shift behavior and neural outcomes observable in adulthood. In contrast, no studies to date demonstrate a causal link between early adversity and trajectories of neural development in humans. The presence of sensitive and responsive caregivers early in development not only provides young children with safety, but also provides sensory, motoric, linguistic, and social stimulation that fosters learning (Gee & Cohodes, 2021; McLaughlin et al., 2017; Sheridan & McLaughlin, 2016). In contrast, the absence of an invested caregiver deprives children of the back and forth interactions that limits opportunities for early learning that are critical for developing typical neural architecture (Rosen et al., 2018; Sheridan et al., 2012). In the current study, we present evidence from a randomized control trial linking profound psychosocial deprivation in early childhood to later changes in cortical development. Using longitudinal data from the Bucharest Early Intervention Project, we show that early randomization to high-foster care results in a shifted neurodevelopmental trajectory from childhood through adolescence and in differences in neural structure in late adolescence among previously-institutionalized children. We observe changes in cortical structure due to randomization to foster care in the lateral and medial prefrontal cortex and in white matter tracts connecting prefrontal and parietal cortex. Exposure to psychosocial deprivation in the form of institutional rearing is associated with a wide range of adverse long-term outcomes, including impaired cognitive abilities (Bos et al., 2009; Sheridan et al., 2018; Tibu et al., 2016) and increased psychopathology (Humphreys et al., 2015; Zeanah et al., 2009). Here, we further demonstrate that observed changes in prefrontal cortical development resulting from prolonged exposure to institutionalization are associated with higher externalizing psychopathology and reduced cognitive function in adolescence. Specifically, thickness in the ACC was positively associated with externalizing factor scores (β = .22, t = 2.02, p = .047, f2= .10) but not the ‘p’ factor or internalizing factor at age 16. In contrast thickness in the IFG was associated with IQ (β = .24, t = -1.97, p = .05, f2= .055). Reflecting the impact of prolonged institutionalization on cortical structure, thicker ACC at 16 years was associated with increased externalizing psychopathology at age 16 and thinner cortex in the IFG at 16 years was associated with higher IQ at age 18. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the lasting neurodevelopmental consequences associated with early-life deprivation. Additional associations with behavioral outcomes demonstrate the real-world consequences of cortical changes subsequent to severe deprivation.

Authors

• Margaret A. Sheridan, University of North Carolina at Chapel Hill
  Presenting Author

• Mark Wade, University of Toronto

• Kathryn L. Humphreys, Vanderbilt University

• Kathryn Garrisi, University of North Carolina at Chapel Hill

• Cora E Mukerji, Bryn Mawr College

• Kinjal Patel, University of North Carolina at Chapel Hill

• Nathan A Fox, University of Maryland - College Park

• Charles H Zeanah, Tulane University

• Charles A. Nelson, Harvard Medical School

• Katie McLaughlin, Harvard University