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.

This study seeks to understand and document how people recovering from opioid addiction communicate about health and identity in the context of a methadone clinic. This project emerges in response to the rising incidence of opioid addiction and overdose death in the U.S. and suggests there is an urgent theoretical and practical calling for bringing forth the stories of people experiencing addiction and recovery. Guided by the structure-centered approach (SCA) to health communication, this study employs a thematic narrative analysis through interviews with 4 methadone maintenance treatment (MMT) patients about the meanings of health, recovery, and identity. With respect to how methadone patients communicate about health and identity, study findings reveal three key themes, which I distinguish as: 1) health as normalcy; 2) health as lack of resources; and 3) recovering the self, (be)longing, and health citizenship. It is through an understanding of these themes that this project contributes, in several meaningful ways, to research and praxis on health communication in addiction treatment spaces. Limitations of research design and considerations for future research projects on health and addiction are provided.

Both genetic and environment factors influence susceptibility to substance use disorders. However, the genetic basis of these disorders is largely unknown. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene for reduced methamphetamine (MA) stimulant sensitivity. Mutation (heterozygous deletion of a small region in the first coding exon) in Hnrnph1 also decreased MA reinforcement, reward, and dopamine release. 5’UTR genetic variants in Hnrnph1 support reduced 5’UTR usage and hnRNP H protein expression as a molecular mechanism underlying the reduced MA-induced psychostimulant response. Interestingly, Hnrnph1 mutant mice show a two-fold increase in hnRNP H protein in the striatal synaptosome with no change in whole tissue level. Proteome profiling of the synaptosome identified an increase in mitochondrial complex I and V proteins that rapidly decreased with MA in Hnrnph1 mutants. In contrast, the much lower level of basal mitochondrial proteins in the wild-type mice showed a rapid, MA-induced increase. Altered mitochondrial proteins associated with the Hnrnph1 mutation may contribute to reductions in MA behaviors. hnRNP H1 is an abundant RNA-binding protein in the brain, involved in all aspect of post-transcriptional regulation. We examined both baseline and MA-induced changes in hnRNP H-RNA interactions to identify targets of hnRNP H that could comprise the neurobiological mechanisms of cellular adaptations occurring following MA exposure. hnRNP H post-transcriptionally regulates a set of mRNA transcripts in the striatum involved in psychostimulant-induced synaptic plasticity. MA treatment induced opposite changes in binding of hnRNP H to these mRNA transcripts between Hnrnph1 mutants versus wild-types. RNA-binding, transcriptome, and spliceome analyses triangulated on hnRNP H binding to the 3’UTR of Cacna2d2, an upregulation of Cacna2d2 transcript, and decreased 3’UTR usage of Cacna2d2 in response to MA in the Hnrnph1 mutants. Cacna2d2 codes for a presynaptic, voltage-gated calcium channel subunit that could plausibly regulate MA-induced dopamine release and behavior. The multi-omics datasets point to a dysregulation of mitochondrial function and interrelated calcium signaling as potential mechanisms underlying MA-induced dopamine release and behavior in Hnrnph1 mutants.

Orientador: Érico Bruno Viana Campos / Resumo: O ensaio em questão utiliza o mito do Santo Graal como fio narrativo para estabelecer uma comparação do funcionamento adicto com o funcionamento do consumidor – segundo os imperativos da sociedade contemporânea. Analisamos a droga enquanto objeto no decorrer da história da humanidade e nos propomos a pensar na relação de objeto estabelecida através do consumo na atualidade, balizados por referenciais da psicanálise. / Abstract: The essay in question uses the Holy Grail myth as a narrative thread to make a comparison of addictive functioning with consumer functioning - according to the imperatives of contemporary society. We analyze the drug as an object throughout the history of humanity and propose to think about the object relation established through consumption today, based on references of psychoanalysis. / Mestre

Religiousness has been shown to have an inverse relationship with at least some types of addiction. The present study examined whether intrinsic religiousness predicts substance addiction in a sample of participants that included mostly undergraduate students from the Appalachian region, as well as some participants surveyed with the use of social media advertisements. Intrinsic religiousness has been defined as internalizing the tenets of one’s faith. Participants self-reported their religiousness using the Religious Surrender and Attendance Scale – 3 (RSAS-3), which has been shown to measure intrinsic religiousness. Substance use was measured by the TCU Drug Screen V (TCUDS). Religiousness, as measured by the RSAS-3, predicted lower levels of substance use addiction as measured by the TCUDS both continuously and dichotomized: X2 (1, N=517) =8.296, p=.004. The odds ratio for the model was 3.724 95% CI [1.305, 10.625] meaning that the odds of being addicted to a substance was 3.724 times more likely for someone who did not meet the threshold for being high in religious commitment than for someone who did. The present study extends findings regarding religiousness and addiction but further research should be done to analyze different theological traditions and their relationship with health outcomes.

INTRODUCTION: Drug overdose death is now the leading cause of mortality among homeless adults in Boston, with opioids implicated in a majority of those deaths. Harm reduction interventions help minimize the risks associated with substance use, and are critical in supporting individuals with substance use disorder. Medical monitoring programs are an effective harm reduction strategy that work to prevent fatal drug overdoses and keep people safe while still actively using. METHODS: Visit data from the Supportive Place for Observation and Treatment (SPOT) was compiled and analyzed. The two measures of interest were the count of referrals to substance use disorder treatment and the count of visits prior to the first referral to treatment. Chi-square tests of independence, odds ratios, and binary logistic regression models were used to describe the association between factors of interest and referrals to substance use disorder treatment. RESULTS: Gender and age did not show any significant association to a connection to treatment. Overdose history (Adjusted Odds Ratio 6.59), reported stimulant use (AOR 2.59), and documented health or harm reduction education (AOR 5.14) were all associated with increased odds of being referred to substance use disorder treatment. Heavy sedation (AOR 0.55) was associated with decreased odds of a treatment referral.When examining factors associated with rapid connection to treatment, male gender (OR 1.87) was associated with increased odds, while overdose history (AOR 0.42) was associated with decreased odds. DISCUSSION: The two most impactful factors associated with increased odds of connecting to substance use disorder treatment were reported overdose history and documented education. Both of these factors suggests that a strength of SPOT is its ability to form and maintain meaningful connections with participants. One way that SPOT could improve referral outcomes would be to increase its ability to engage participants, such as through the recruitment of more harm reduction specialists or peer recovery coaches.

The purpose of the current study was to provide both additional evidence of the psychometric properties of the TIPSA by examining reliability and validity coefficients, and to add to the empirical evidence for the application of betrayal trauma theory outside the context of complex and/or historical trauma. It was hypothesized that internal-consistency coefficients for the TIPSA would exceed 0.70; the TIPSA and the PTSD Checklist for DSM 5 (PCL-5) would be significantly positively correlated; the TIPSA and the Composite Codependency Scale (CCS) would not be significantly correlated; and that neither Adverse Childhood Experiences (ACE) nor Benevolent Childhood Experiences (BCE) scores would be significantly correlated with, or have a significant effect on TIPSA or PCL-5 scores. This study was conducted using anonymous survey data from192 female participants who self-identified as partners of sex addicts. Participants completed the TIPSA, PCL-5, CCS, ACE, and BCE measures. All reliability estimates for the TIPSA were above 0.70, as were all total-scale reliability estimates for the additional measures. Correlation between the TIPSA and PCL-5 produced a Pearson's r of 0.851 (p = 5.541 E-55), which indicated a large effect size. Correlations with additional measures produced statistically significant, yet small to weak, effect sizes (CCS: r = 0.292; ACE: r = -0.173; BCE: r = 0.244). Based on study results, there appears to be sufficient evidence to establish convergent validity of the TIPSA as a measure of trauma symptoms. Moreover, statistical evidence indicates only a weak relationship between the TIPSA and the CCS, thus establishing divergent validity of the TIPSA. Finally, neither the BCE nor the ACE was strongly correlated with the TIPSA, which adds to the empirical evidence for utilizing betrayal trauma theory outside the context of complex trauma, and also serves to provide additional evidence for divergent validity of the TIPSA.

Loot boxes are items in video games that contain a randomized reward. Some of them can be purchased with real-world money. In recent years loot boxes have become very common in almost all of the top games. Because of its similarities to gambling there have been thoughts on branding loot boxes as a form of gambling. Some countries have already taken this matter into their own hands and banned certain loot boxes.But there are different loot boxes with different features. This study looks at what aspects of purchasing loot boxes correlate to form of gambling. By researching the top 10 games on steam and their loot boxes combined with a literature study. In conclusion it was found that the main features of Loot Boxes that correlate to a form of gambling are features that try to mirror or copy features from Electronic Game Machines or different casino games.

Mitochondrial DNA mutations accumulate with age and may play a role in stem cell aging as suggested by the premature aging phenotype of mitochondrial DNA polymerase gamma (POLG) exonuclease-deficient mice. Therefore, E1A immortalized murine embryonic fibroblasts (MEFs) from POLG exonuclease-deficient and wild-type (WT) mice were constructed. Surprisingly, when some E1A immortalized MEF lines were cultured in pyruvate-containing media they slowly became addicted to the pyruvate. The POLG exonuclease-deficient MEFs were more sensitive to several mitochondrial inhibitors and showed increased reactive oxygen species (ROS) production under standard conditions. When cultured in pyruvate-containing media, POLG exonuclease-deficient MEFs showed decreased oxygen consumption compared to controls. Increased AMP-activated protein kinase (AMPK) signaling and decreased mammalian target of rapamycin (mTOR) signaling delayed aging and influenced mitochondrial function. Therefore, the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK activator, or rapamycin, an mTOR inhibitor, on measures of mitochondrial function were determined. Rapamycin treatment transiently increased respiration only in WT MEFs and, under most conditions, increased ATP levels. Short term AICAR treatment transiently increased ROS production and, under most conditions, decreased ATP levels. Chronic AICAR treatment decreased respiration and ROS production in WT MEFs. These results demonstrate the context-dependent effects of AICAR and rapamycin on mitochondrial function.

Background: Smartphone addiction can have negative consequences such as anxiety, depression, insomnia, and a loss of social connectivity. Understanding smartphone addiction is still in its early stages, but self-regulation and attention deficit hyperactivity disorder (ADHD) symptoms are two established risk factors. Exploring these risk factors and their impact on individuals’ well-being may help prevent smartphone addiction. Objective: This study aims to (1) explore the relationship between smartphone addiction and psychological and social well-being (e.g., friendship validation and caring, and friendship and intimate exchange) among adolescents. (2) Examine whether self-regulation mediates the relationship between smartphone addiction and psychological well-being and social well-being. (3) Examine whether attention mediates the relationship between smartphone addiction and psychological well-being and social well-being. Methods: This was a cross-sectional study conducted in middle school in Victoria, British Columbia, Canada. Students (Grade 6-8) completed an online survey that measured smartphone addiction, attention, self-regulation, and psychological and social well-being. A bivariate correlational analysis was used to examine the relationship between smartphone addiction, self-regulation, attention psychological well-being, and social well-being. Multiple mediation analyses were used to perform the mediation between smartphone addiction, attention, self-regulation, and psychological and social well-being. Results: The bivariate correlation showed significant negative associations between smartphone addiction and attention, self-regulation, psychological well-being, and friendship validation and caring. Smartphone addiction did not have a significant relationship with friendship intimate exchange. The mediation analysis showed that attention was a significant mediator between smartphone addiction and psychological well-being (indirect effect= -.102; 95% CI -.142, -.066) and between smartphone addiction and friendship validation and caring (indirect effect= -.056; 95% CI -.093, -.024; direct effect= -.071; 95% CI -.155, .013). Attention did not significantly mediate the relationship between smartphone addiction and the friendship intimate exchange aspect of social well-being (indirect effect= -.005; 95% CI -.026, .016). Self-regulation showed a significant partial mediation between smartphone addiction and psychological well-being (indirect effect= -.016; 95% CI -.034, -.002). Self-regulation did not significantly mediate the relationship between smartphone addiction and friendship validation and caring (indirect effect=-.014; 95% CI -.034, .001) and friendship intimate exchange (indirect effect=-.001; 95% CI -.007, .007). Conclusion: The results indicated that the negative relationship between smartphone addiction and psychological well-being can be partially explained by adolescents’ attention and self-regulation abilities. The negative relationship between smartphone addiction and social well-being (validation and caring) can be partially explained by adolescents’ attention. However, both aspects of social well-being (validation and caring and intimate exchange) were not impacted by self-regulation. This study identified potential mediators that may be used for future interventions to prevent smartphone addiction and promote wellbeing. / Graduate