Lee, Kristin2017-12-182017-12-182015-08http://hdl.handle.net/10125/51062M.S. University of Hawaii at Manoa 2015.Includes bibliographical references.Background Common structural brain abnormalities reported in substance use related (SUD) related regions were found in children with family history (FH) of SUD. However, the effect of FH-degree of SUD is not well examined. Therefore, the influence of degree of FH of substance use problems (SUP) on cortical morphometry was investigated. Methods 921 typically developing children (ages 3-20 years old; 470 boys/451 girls) had structural MRI and executive functions measures. The influence of first and/or second-degree FH (Any-FH) and the separate effects of first-degree (First-FH) and second-degree FH of SUP (Second-FH) on cortical structures were investigated using FreeSurfer. The relationships between FH related cortical alterations and executive functioning were examined. Sex interactions with FH-degree on cortical morphometry were also investigated. Results Any-FH children had volume alterations mediated by changes in surface areas. FH children have larger left prefrontal and right superior areas and volumes when compared to No-FH children. First-FH and Second-FH show a variable effect on cortical volumes particularly for regions in the posterior frontal and anterior parietal regions as well as the right fusiform gyrus. Sex differences for cortical morphometry between First-FH and Second-FH children were widespread, but strongest in the left frontal regions. The left supramarginal and right fusiform gyri, regions specifically reduced for First-FH children, were also related to differential executive functioning and this same association was found in First-FH girls. Importantly, the majority of results remained even when controlling for confounders such as ADHD. Conclusion The children with FH of SUP have overall differences in prefrontal regions. First-FH and Second-FH children showed different morphometric alterations in parietal and temporal regions, which may contribute to deficits in executive function. Further studies are need to explore the sex-specific influences in cortical morphometry of children with FH of SUP, and the possible consequences on cognition.engSubstance Use ProblemsFamily HistoryBrainImagingThesis