Dissertation
Assessment of brain morphology and resting state functional connectivity in children with a family history of alcohol use disorder
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2021
DOI: 10.17077/etd.005920
Abstract
Alcohol is the third leading preventable cause of death in the United States. Alcohol Use Disorder (AUD) is also highly prevalent in the United States, with approximately 14.1 million adults and 414,000 adolescents being affected. It is, therefore, extremely important to understand the biological and psychological factors conferring increased risk of developing AUD. One particularly important factor is family history of AUD, as studies have suggested that the heritability of AUD is high, approximately 30%- 50%. Although family history of AUD is one of the most important risk factors for AUD development, little is known about differences in brain structure and functional networks in individuals with a family history of AUD. The present project aimed to identify robust, reliable, and generalizable associations between brain structure and functional connectivity in relation to family history status. Toward this aim, we have utilized data from the Adolescent Brain Cognitive Development (ABCD) study and identified 524 Family History Positive (FHP) and 524 Family History Negative (FHN) who were substance naive and were matched on sex, age, race, handedness, and pubertal status. Furthermore, participants had minimal prenatal drug exposure, no history of traumatic brain injury or major psychological disorders (psychosis, bipolar, or substance use disorder). In addition to utilizing neuroimaging data, we also compared FHP and FHN individuals on psychiatric problems and cognitive performance. Machine learning models were also tested to examine if family history status can be predicted from brain imaging or non-imaging data in a generalizable manner. We found that parents with AUD had lower household income and lower educational attainment. In addition, compared to FHN children, FHP children also showed higher externalizing problems (heightened aggressive and rule-breaking behaviors), internalizing problems (mood problems and somatic complaints), thought problems (psychosis-like problems), and social problems. Interestingly, there were no significant group differences in cognitive performance, brain morphology, and resting state functional connectivity between FHP and FHN. Results from machine learning models were consistent with results from univariate analyses. Specifically, machine learning models with imaging data, which did not show any univariate significant group differences, were not able to predict family history status. In contrast, using variables that were significantly different between FHP and FHN in univariate analyses (psychiatric problems and socioeconomic status, or SES), machine learning models performed better than chance (65% accuracy, p = .0002) when predicting family history status in a held-out dataset. These results suggested that extant reports on significant cognitive and neural alterations in FHP youths may likely represent effects of substance use or substance exposure in utero. Controlling for offspring’s substance use or prenatal substance exposure, the effects of family history of AUD on cognition and brain structure and functional connectivity in children (if exist) are very small (| d | < 0.2) and might not be detectable with a sample size of approximately 1000. Overall, our results highlight the association between family history of AUD and lower SES, which can have significant implications on both physical and psychological development of the offspring, and may later interact with family history to predict offspring’s future substance use. Our results also highlight the association between family history and increased psychiatric problems, which may be attributable to a high stress, high conflict family environment, as well as possible genetic transmission of a general vulnerability to heightened psychiatric problems in FHP individuals. Future research is needed to determine when cognitive deficits and neural alterations start to emerge and become more robust in FHP individuals.
Details
- Title: Subtitle
- Assessment of brain morphology and resting state functional connectivity in children with a family history of alcohol use disorder
- Creators
- Tien Thi Quynh Tong
- Contributors
- Daniel S O'Leary (Advisor)Jatin G. Vaidya (Advisor)Michelle W. Voss (Committee Member)Kai Hwang (Committee Member)Jacob J. Michaelson (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Neuroscience
- Date degree season
- Summer 2021
- DOI
- 10.17077/etd.005920
- Publisher
- University of Iowa
- Number of pages
- xv, 118 pages
- Copyright
- Copyright 2021 Tien Thi Quynh Tong
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 93-118)
- Public Abstract (ETD)
Alcohol use disorder (AUD) is a brain disease that takes a significant toll on individuals suffering from the disease as well as close family members. Importantly, AUD runs in families: a child with a parent with AUD is much more likely to develop AUD themselves. As familial AUD is one of the most important risk factors for alcohol addiction, this project aimed to investigate differences between 9- and 10-year-old children with and without a family history of AUD in terms of brain structure and brain networks, socioeconomic status, cognitive performance, and psychiatric problems. The results showed that children with a family history of AUD (i.e., family history positive) tended to come from families with lower socioeconomic status. They also had more psychiatric problems (e.g., having more aggressive/rule-breaking behaviors, more mood problems) compared to children without such a family history (i.e., family history negative). However, relative to family history negative children, family history positive children did not display any changes in brain structure, brain networks, or cognitive performance (e.g., memory, attention, language ability, or ability to process information quickly).
- Academic Unit
- Interdisciplinary Graduate Program in Neuroscience
- Record Identifier
- 9984124361002771
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