All ETDs from UAB

Advisory Committee Chair

David C Knight

Advisory Committee Members

Sylvie Mrug

Karen Cropsey

Peter S Hendricks

Jared Younger

Document Type

Dissertation

Date of Award

2022

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

Adolescent substance use is common and may disrupt structural and functional brain development given that adolescence is a period of substantial neural maturation. Neurodevelopmental disruptions may be most pronounced within brain regions that undergo substantial development during adolescence (e.g., prefrontal cortex [PFC]) and regions that are integral to reward networks (e.g., nucleus accumbens [NAcc]). This project used latent growth curve models (LGCM) coupled with neuroimaging techniques to investigate relationships between adolescent substance use and young adult brain structure and functional connectivity. Substance use was assessed at 4 timepoints (ages 11, 13, 16, 19) in 1,594 participants. A subset of participants (N=350) then completed structural (gray matter volume) and functional (resting state functional connectivity [rsFC]) neuroimaging. Trajectories (i.e., patterns of use over time) of substance use were constructed by using LGCMs to characterize each participant’s alcohol, tobacco, and cannabis use at age 14, progression of use, and acceleration of use across adolescence. Analyses investigated the relationships adolescent substance use trajectories have with brain structure and functional connectivity in young adulthood. Gray matter volume varied with substance use trajectories within subcortical, but not cortical, regions. Specifically, hippocampal volume had a positive relationship with age 14 alcohol use. Gray matter volume was not associated with trajectories of tobacco or cannabis use. Thus, the relationship between substance use and brain structure was limiv ited to alcohol use at age 14. Relationships between substance use trajectories and rsFC were also observed. Specifically, alcohol, tobacco, and cannabis use at age 14 was associated with NAcc rsFC with the hippocampus, parahippocampal gyrus, and several additional PFC regions. Further, the progression of alcohol, tobacco, and cannabis use was linked with NAcc rsFC with the parahippocampal gyrus, amygdala, and several PFC regions. Finally, acceleration of alcohol, tobacco, and cannabis use was associated with NAcc rsFC with the hippocampus, parahippocampal gyrus, and several PFC regions. Thus, rsFC varied with substance use trajectories that reflect age of initiation, progression of use, and acceleration of use across adolescence. Taken together, the results of this project suggest that gray matter volume and rsFC in young adulthood vary with adolescent substance use.

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