Research Publications

Abstract

Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hormones, sports participation, and social/economic disparities on brain development as well as their association with the emergence and progression of substance use and mental illness including suicide risk. Thus, the Adolescent Brain Cognitive Development study was created to answer the most pressing public health questions of our day.

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The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006-2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study.

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Observational neuroimaging studies with children and adolescents may identify neurological anomalies and other clinically relevant findings. Planning for the management of this information involves ethical considerations that may influence informed consent, confidentiality, and communication with participants about assessment results. Biomedical ethics principles include respect for autonomy, beneficence, non-maleficence, and justice. Each project presents unique challenges. The Adolescent Brain and Cognitive Development study (ABCD) collaborators have systematically developed recommendations with written guidelines for identifying and responding to potential risks that adhere to biomedical ethics principles. To illustrate, we will review the ABCD approach to three areas: (1) hazardous substance use; (2) neurological anomalies; and (3) imminent potential for self-harm or harm to others. Each ABCD site is responsible for implementing procedures consistent with these guidelines in accordance with their Institutional Review Board approved protocols, state regulations, and local resources. To assure that each site has related plans and resources in place, site emergency procedures manuals have been developed, documented and reviewed for adherence to ABCD guidelines. This article will describe the principles and process used to develop these ABCD bioethics and medical oversight guidelines, the concerns and options considered, and the resulting approaches advised to sites.

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Substance use disorders (SUD) can be considered developmental disorders in light of their frequent origins in substance initiation during adolescence. Cross-sectional functional magnetic resonance imaging (fMRI) studies of adolescent substance users or adolescents with SUD have indicated aberrations in brain structures or circuits implicated in motivation, self-control, and mood-regulation. However, attributing these differences to the neurotoxicological effects of chronic substance use has been problematic in that these circuits are also aberrant in at-risk children, such as those with prenatal substance exposure, externalizing disorders (such as conduct disorder), or prodromal internalizing disorders such as depression. To better isolate the effects of substance exposure on the adolescent brain, the newly-launched Adolescent Brain Cognitive Development (ABCD) study, funded by the National Institutes of Health, will follow the neurodevelopmental trajectories of over 11,000 American 9/10-year-olds for 10 years, into emerging adulthood. This study will provide a rich open-access dataset on longitudinal interactions of neurodevelopment, environmental exposures, and childhood psychopathology that confer addiction risk. The ABCD twin study will further clarify genetic versus experiential influences (e.g., substance use) on neurodevelopmental and psychosocial outcomes. Neurocircuitry thought to regulate mood and behavior has been directly normalized by administration of psychoactive medications and by cognitive therapies in adults. Because of this, we contend that ABCD project data will be a crucial resource for prevention and treatment of SUD in adolescence because its cutting-edge neuroimaging and childhood assessments hold potential for discovery of additional targetable brain differences earlier in development that are prognostic of (or aberrant in) SUD. The ABCD sample size will also have the power to illuminate how sex differences, environmental interactions and other individual differences interact with neurodevelopment to inform treatment in different groups of adolescents.

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