Altered Associations between White Matter Structure and Psychopathology in Previously Institutionalized Adolescents

Abstract

Previously institutionalized adolescents show increased risk for psychopathology, though placement into high-quality foster care can partially mitigate this risk. White matter (WM) structure is associated with early institutional rearing and psychopathology in youth. Here we investigate associations between WM structure and psychopathology in PI youth. Adolescent psychopathology data were assessed using the MacArthur Health and Behavior Questionnaire. Participants underwent diffusion MRI, and data were processed using fixel-based analyses. General linear models investigated interactions between institutionalization groups and psychopathology on fixel metrics. Supplementary analyses also examined the main effects of psychopathology and institutionalization group on fixel metrics. Institutionally reared (‘Ever–Institutionalized’) subjects included 41 randomized to foster care (Mage=16.6), and 40 to care-as-usual (Mage=16.7)). In addition, 33 participants without a history of institutionalization were included as a reference group (Mage=16.9). Ever–Institutionalized adolescents displayed altered general psychopathology­­–fixel associations within the cerebellar peduncles, inferior longitudinal fasciculi, corticospinal tract, and corpus callosum, and altered externalizing–fixel associations within the cingulum and fornix. Our findings indicate brain–behavior associations reported in the literature may not be generalizable to all populations. PI youth may develop differential optimal brain development, leading to altered neural correlates of psychopathology that are still apparent in adolescence.

Note:

Funding Information: John D. and Catherine T. MacArthur Foundation, the Help the Children of Romania, Inc. Foundation, the Binder Family Foundation, the Palix Foundation, the Jacobs Foundation, and the National Institute of Mental Health of the National Institutes of Health under Award R01MH091363 (to Charles A. Nelson). Work supported by NIMH Intramural Research and Training Award ZIA-MH002782.

Conflict of Interests: Dr. Fox has received grant support from the National Institute of Mental Health (NIMH), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Science Foundation (NSF), the National Institutes of Health Environmental influences on Child Health Outcomes (NIH ECHO) consortium, the Russell Sage Foundation, and the Lumos Foundation. He has received royalties from Guilford Press and Harvard University Press. He has received honoraria for lectures to professional audiences. Dr. Zeanah has received grant support from the NIMH, the Palix Foundation, the Irving Harris Foundation, the Substance Abuse and Mental Health Services Administration (SAMHSA), and the Lumos Foundation. He has received royalties from Guilford Press and Harvard University Press. He has received honoraria for lectures to professional audiences. Dr. Nelson has received grant support from the National Institutes of Health (NIH), the Jacobs Foundation, the John D. and Catherine T. MacArthur Foundation, the James S. McDonnel Foundation, the Binder Family Foundation, the Lumos Foundation, the Bill and Melinda Gates Foundation, and Harvard University. He has received royalties from the Massachusetts Institute of Technology and Harvard University Press. He has received honoraria for lectures to professional audiences and legal consulting fees.

Ethical Approval: Children’s legal guardians provided signed informed consent (children age 8 years and older provided written or verbal assent). Ethics approval was obtained from the institutional revie

Keywords: early deprivation, adolescent psychopathology, dMRI, white matter