Identifying neurobiological predictors of substance use onset during adolescence
MetadataShow full item record
BACKGROUND: Early initiation of alcohol and other substance use is considered one of the most important risk factors for the later development of an alcohol use disorder. However, it is not yet well understood to what extent this increased risk reflects neurobiological changes driven by the use itself, and to what extent it reflects pre-existing traits and patterns. This dissertation therefore aims to identify neurobiological and neuropsychological markers that exist prior to the initiation of substance use and may confer risk for earlier use onset. Specifically, the research places a focus on the domains of inhibitory control and learning and memory. METHODS: Adolescents (n=81) were enrolled into the study prior to the initiation of alcohol or other drug use at 13-14 years old to complete baseline brain imaging. Neuroimaging included acquisition of structural magnetic resonance imaging (MRI) and task functional magnetic resonance imaging (fMRI) during response inhibition (emotional Go-NoGo) and spatial memory (virtual Morris Water Task) tasks. Participants also completed a neuropsychological battery that included the California Verbal Learning Test Children’s Version (CVLT-C). Subjects were then followed for up to three years via quarterly online surveys in order to assess initiation of alcohol and substance use. Those who went on to endorse initiating substance use prior to reaching 16 years of age were included in an initiating group (IG, n=21) and those who turned 16 having continuously denied substance use were included in a non-initiating comparison group (CG, n=24). RESULTS: Performance measures on the emotional Go-NoGo (NoGo trial accuracy, Go trial accuracy, Go trial reaction time) showed no significant group differences between IG and CG. Functional brain activation differences, however, were observed in bilateral inferior frontal gyrus (IFG), with CG showing greater activation relative to IG on inhibitory (NoGo) trials with negative versus neutral emotional background images (Negative NoGo>Neutral NoGo). Performance on learning trials for the virtual Morris Water Task, completed offline prior to scanning, showed a subtle learning difference between groups, but no performance or functional brain activation differences were observed on Retrieval or Motor control trials completed during scanning. Performance on the neuropsychological test of verbal learning and memory (CVLT-C) indicated worse learning and memory in IG relative to CG (fewer correct responses on both the Long-Delay Free-Recall and the Recognition trials). CONCLUSIONS: These findings help characterize neurobiological and neuropsychological patterns that exist prior to exposure to substances, and thus may help differentiate adolescents who go on to initiate substance use earlier in adolescence from those who do not. Results suggest brain activation differences in frontal regions may predate use, while activation differences in hippocampal memory systems (observed in some cross-sectional studies of alcohol use) may not. These data help clarify questions of causality and provide a foundation for informing strategies for prevention and intervention efforts in maladaptive alcohol and substance use.