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- Genre: Doctoral Dissertation
Description
The present study utilized longitudinal data from a high-risk community sample (n=254, 52.8% female, 47.2% children of alcoholics, 74% non-Hispanic Caucasian) to test questions concerning the effects of genetic risk, parental knowledge, and peer substance use on emerging adult substance use disorders (SUDs). Specifically, this study examined whether parental knowledge and peer substance use mediated the effects of parent alcohol use disorder (AUD) and genetic risk for behavioral undercontrol on SUD. The current study also examined whether genetic risk moderated effects of parental knowledge and peer substance use on risk for SUD. Finally, this study examined these questions over and above a genetic "control" which explained a large proportion of variance in the outcome, thereby providing a stricter test of environmental influences.
Analyses were performed in a path analysis framework. To test these research questions, the current study employed two polygenic risk scores. The first, a theory-based score, was formed using single-nucleotide polymorphisms (SNPs) from receptor systems implicated in the amplification of positive effects in the presence of new/exciting stimuli and/or pleasure derived from using substances. The second, an empirically-based score, was formed using a data-driven approach that explained a large amount of variance in SUDs. Together, these scores allowed the present study to test explanations for the relations among parent AUD, parental knowledge, peer substance use, and SUDs.
Results of the current study found that having parents with less knowledge or an AUD conferred greater risk for SUDs, but only for those at higher genetic risk for behavioral undercontrol. The current study replicated research findings suggesting that peer substance use mediated the effect of parental AUD on SUD. However, it adds to this literature by suggesting that some mechanism other than increased behavioral undercontrol explains relations among parental AUD, peer substance use, and emerging adult SUD. Taken together, these findings indicate that children of parents with AUDs comprise a particularly risky group, although likelihood of SUD within this group is not uniform. These findings also suggest that some of the most important environmental risk factors for SUDs exert effects that vary across level of genetic propensity.
Analyses were performed in a path analysis framework. To test these research questions, the current study employed two polygenic risk scores. The first, a theory-based score, was formed using single-nucleotide polymorphisms (SNPs) from receptor systems implicated in the amplification of positive effects in the presence of new/exciting stimuli and/or pleasure derived from using substances. The second, an empirically-based score, was formed using a data-driven approach that explained a large amount of variance in SUDs. Together, these scores allowed the present study to test explanations for the relations among parent AUD, parental knowledge, peer substance use, and SUDs.
Results of the current study found that having parents with less knowledge or an AUD conferred greater risk for SUDs, but only for those at higher genetic risk for behavioral undercontrol. The current study replicated research findings suggesting that peer substance use mediated the effect of parental AUD on SUD. However, it adds to this literature by suggesting that some mechanism other than increased behavioral undercontrol explains relations among parental AUD, peer substance use, and emerging adult SUD. Taken together, these findings indicate that children of parents with AUDs comprise a particularly risky group, although likelihood of SUD within this group is not uniform. These findings also suggest that some of the most important environmental risk factors for SUDs exert effects that vary across level of genetic propensity.
ContributorsBountress, Kaitlin (Author) / Chassin, Laurie (Thesis advisor) / Crnic, Keith (Committee member) / Lemery-Chalfant, Kathryn (Committee member) / MacKinnon, David (Committee member) / Arizona State University (Publisher)
Created2015
Description
The current study utilized data from two longitudinal samples to test mechanisms in the relation between a polygenic risk score indexing serotonin functioning and alcohol use in adolescence. Specifically, this study tested whether individuals with lower levels of serotonin functioning as indexed by a polygenic risk score were vulnerable to poorer self-regulation, and whether poorer self-regulation subsequently predicted the divergent outcomes of depressive symptoms and aggressive/antisocial behaviors. This study then examined whether depressive symptoms and aggressive/antisocial behaviors conferred risk for later alcohol use in adolescence, and whether polygenic risk and effortful control had direct effects on alcohol use that were not mediated through problem behaviors. Finally, the study examined the potential moderating role of gender in these pathways to alcohol use.
Structural equation modeling was used to test hypotheses. Results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create serotonin (5-HT) polygenic risk scores, wherein higher scores reflected lower levels of 5-HT functioning. Data from three time points were drawn from each sample, and all paths were prospective. Findings suggested that 5-HT polygenic risk did not predict self-regulatory constructs. However, 5-HT polygenic risk did predict the divergent outcomes of depression and aggression/antisociality, such that higher levels of 5-HT polygenic risk predicted greater levels of depression and aggression/antisociality. Results most clearly supported adolescents’ aggression/antisociality as a mechanism in the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. These pathways to alcohol use might be the most salient for boys with low levels of socioeconomic status.
Results are novel contributions to the literature. The previously observed association between serotonin functioning and alcohol use might be due, in part, to the fact that individuals with lower levels of serotonin functioning are predisposed towards developing earlier aggression/antisociality. Results did not support the hypothesis that serotonin functioning predisposes individuals to deficits in self-regulatory abilities. Findings extend previous research by suggesting that serotonin functioning and self-regulation might be transdiagnostic risk factors for many types of psychopathology.
Structural equation modeling was used to test hypotheses. Results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create serotonin (5-HT) polygenic risk scores, wherein higher scores reflected lower levels of 5-HT functioning. Data from three time points were drawn from each sample, and all paths were prospective. Findings suggested that 5-HT polygenic risk did not predict self-regulatory constructs. However, 5-HT polygenic risk did predict the divergent outcomes of depression and aggression/antisociality, such that higher levels of 5-HT polygenic risk predicted greater levels of depression and aggression/antisociality. Results most clearly supported adolescents’ aggression/antisociality as a mechanism in the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. These pathways to alcohol use might be the most salient for boys with low levels of socioeconomic status.
Results are novel contributions to the literature. The previously observed association between serotonin functioning and alcohol use might be due, in part, to the fact that individuals with lower levels of serotonin functioning are predisposed towards developing earlier aggression/antisociality. Results did not support the hypothesis that serotonin functioning predisposes individuals to deficits in self-regulatory abilities. Findings extend previous research by suggesting that serotonin functioning and self-regulation might be transdiagnostic risk factors for many types of psychopathology.
ContributorsWang, Frances Lynn (Author) / Chassin, Laurie (Thesis advisor) / Eisenberg, Nancy (Committee member) / Lemery-Chalfant, Kathryn (Committee member) / MacKinnon, David (Committee member) / Arizona State University (Publisher)
Created2017
Description
The process of combining data is one in which information from disjoint datasets sharing at least a number of common variables is merged. This process is commonly referred to as data fusion, with the main objective of creating a new dataset permitting more flexible analyses than the separate analysis of each individual dataset. Many data fusion methods have been proposed in the literature, although most utilize the frequentist framework. This dissertation investigates a new approach called Bayesian Synthesis in which information obtained from one dataset acts as priors for the next analysis. This process continues sequentially until a single posterior distribution is created using all available data. These informative augmented data-dependent priors provide an extra source of information that may aid in the accuracy of estimation. To examine the performance of the proposed Bayesian Synthesis approach, first, results of simulated data with known population values under a variety of conditions were examined. Next, these results were compared to those from the traditional maximum likelihood approach to data fusion, as well as the data fusion approach analyzed via Bayes. The assessment of parameter recovery based on the proposed Bayesian Synthesis approach was evaluated using four criteria to reflect measures of raw bias, relative bias, accuracy, and efficiency. Subsequently, empirical analyses with real data were conducted. For this purpose, the fusion of real data from five longitudinal studies of mathematics ability varying in their assessment of ability and in the timing of measurement occasions was used. Results from the Bayesian Synthesis and data fusion approaches with combined data using Bayesian and maximum likelihood estimation methods were reported. The results illustrate that Bayesian Synthesis with data driven priors is a highly effective approach, provided that the sample sizes for the fused data are large enough to provide unbiased estimates. Bayesian Synthesis provides another beneficial approach to data fusion that can effectively be used to enhance the validity of conclusions obtained from the merging of data from different studies.
ContributorsMarcoulides, Katerina M (Author) / Grimm, Kevin (Thesis advisor) / Levy, Roy (Thesis advisor) / MacKinnon, David (Committee member) / Suk, Hye Won (Committee member) / Arizona State University (Publisher)
Created2017