Initial Results from a New College Substance Use Prevention Program Targeting Externalizing and Internalizing Traits.

Objective: College students engage in high rates of risky substance use. Standard college prevention strategies focus on providing feedback about current substance use behaviors and harm reduction strategies but do not address the underlying genetically-influenced risk factors impacting these behaviors. We created an online Personalized Feedback Program (PFP) for college students that targets genetically-influenced externalizing and internalizing risk pathways and provides personalized recommendations and campus resources. College students received personalized feedback on four risk domains (Sensation Seeking, Impulsivity, Extraversion, and Neuroticism). Methods: An open trial (n = 300) was conducted at a large public university in spring of 2021 to assess initial responses to the PFP and evaluate intentions related to future substance use and campus resource use. Results: 81% of students in the open trial reported they enjoyed the Personalized Feedback Program. Participants reported intending to use significantly more campus resources after completing the PFP. Among participants that drank, 39% reported they intended to decrease their alcohol consumption and 41% reported they intended to decrease the number of times they get drunk after completing the PFP; these intentions to reduce use after completing the PFP are higher than rates found in previous studies. Conclusion: Preliminary data indicate that the Personalized Feedback Program may be a complementary method to enhance current college substance use prevention programs.

Integrating Theory with Education about Genetic Risk for Alcohol Use Disorder: The Effects of a Brief Online Educational Tool on Elements of the Health Belief Model.

Introduction: The utility of genetic risk information relies on the assumption that individuals will use the information to change behavior to reduce risk of developing health problems. Educational interventions designed to target elements of the Health Belief Model have shown to be effective in promoting behaviors for positive outcomes. Methods: A randomized controlled trial (RCT) was conducted in 325 college students to assess whether a brief, online educational intervention altered elements of the Health Belief Model that are known to be associated with motivations and intentions to change behavior. The RCT included a control condition, an intervention condition that received information about alcohol use disorder (AUD), and an intervention condition that received information about polygenic risk scores and AUD. We used t tests and ANOVA methods to compare differences in beliefs related to the Health Belief Model across study conditions and demographic characteristics. Results: Providing educational information did not impact worry about developing AUD, perceived susceptibility and severity of developing alcohol problems, or perceived benefits and barriers of risk-reducing actions. Individuals in the condition that received educational information about polygenic risk scores and AUD reported higher perceived chance of developing AUD than individuals in the control condition (adj. p < 0.01). Sex, race/ethnicity, family history, and drinking status were associated with several components of the Health Belief Model. Conclusion: Findings from this study demonstrate the need to better design and refine the educational information intended to accompany the return of genetic feedback for AUD to better promote risk-reducing behaviors.

Bridging the gap between genetic epidemiological research and prevention: A randomized control trial of a novel personalized feedback program for alcohol and cannabis use.

BACKGROUND: Risky substance use among college students is widespread and associated with numerous negative consequences. We created an online Personalized Feedback Program (PFP) for college students that targets genetically influenced risk pathways for substance use and provides feedback on four risk domains (Sensation Seeking, Impulsivity, Extraversion, and Neuroticism) along with individualized recommendations and campus resources. METHODS: A pilot randomized controlled trial was conducted to evaluate the effects of the PFP on alcohol and cannabis use. First-year college students were randomized to one of four groups: (1) control, (2) PFP, (3) computer-delivered brief motivational intervention (BMI), and (4) combined group that included both the PFP and BMI (PFP+BMI). Students completed a baseline survey (n=251) that assessed alcohol and cannabis use and program satisfaction. Two follow-up surveys were administered at 30-days and 3-months post-intervention to evaluate longitudinal effects on substance use. RESULTS: Participants reported high satisfaction with the PFP. There were no significant effects of intervention group on alcohol use at the follow-up timepoints, though trends were in the expected direction with participants in the PFP group showing decreased odds of alcohol use. There were significant reductions in cannabis use in the PFP group as compared to other groups. CONCLUSIONS: The PFP was met with high satisfaction and had a positive impact on reducing cannabis use. With cannabis use at a historic high among college-aged adults, further research evaluating the effects of the PFP is warranted.

The impact of receiving polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to reduce drinking.

For the return of polygenic risk scores to become an acceptable clinical practice in psychiatry, receipt of polygenic risk scores must be associated with minimal harm and changes in behavior that decrease one's risk for developing a psychiatric outcome. Data from a randomized controlled trial was used to assess the impact of different levels of hypothetical polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to change drinking behaviors. The analytic sample consisted of 325 participants recruited from an urban, public university. Results demonstrated that there were significant increases in psychological distress as the level of genetic risk for alcohol use disorder increased. In addition, the perceived chance of developing alcohol use disorder significantly increased as the level of genetic risk increased. Promisingly, a greater proportion of participants indicated that they would intend to engage in follow-up behaviors, such as seeking additional information, talking to a healthcare provider about risk, and reducing drinking behaviors, as the level of genetic risk increased. Returning polygenic risk scores for alcohol use disorder in a clinical setting has the potential to promote risk-reducing behavior change, especially with increasing levels of genetic risk. The study was registered on ClinicalTrials.gov (Identifier: NCT05143073).

Returning complex genetic risk information to promote better health-related behaviors: a commentary of the literature and suggested next steps.

Genome-wide association studies aim to identify genetic variants that are associated with a disease phenotype in order to enhance precision medicine efforts. Despite the excitement surrounding the promise of precision medicine and interest among the public in accessing personalized genetic information, there has been little effort dedicated to understanding how complex genetic risk information could be incorporated into clinical practice to inform prevention, screening, and treatment. In this article, we briefly summarize the literature on the impact of receiving genetic risk information on health-related behavior, discuss the limitations of these studies, and outline the challenges that will need to be overcome, along with suggested next steps for future studies, to understand the true promise of precision medicine. The current literature demonstrates that there is no consistent or strong evidence that receiving complex genetic risk information, such as polygenic risk scores, has an impact on behavior; however, there are a number of limitations that may impact the failure to find significant effects associated with receiving genetic feedback. Behavior change is a complex process and simply providing genetic risk information without incorporating a theoretical perspective on behavior change diminishes the potential impact of receiving genetic risk information on actual behavior change. Future studies and interventions which return genetic feedback should be designed using theoretical frameworks of behavior change models to improve the impact of receiving personalized genetic information.

The basis of precision medicine is to use an individual's personal genetic information, such as a polygenic risk score, along with lifestyle information and personal medical history, to promote better health outcomes. The utility of polygenic risk scores relies on the assumption that receiving complex genetic feedback will motivate changes in behavior that reduces one's risk for developing a medical condition. To date, there is no consistent or strong evidence that receiving complex genetic risk information, such as polygenic risk scores, influences behavior change. However, the literature on how to effectively deliver polygenic risk scores is small. Prior studies assessing the impact of receiving complex genetic risk information have several limitations that may impact the failure to find that individuals take action or change health behaviors after receiving genetic feedback. One way to address these limitations is to incorporate theories of behavior change, such as the Health Belief Model, into the way in which genetic risk information is returned. Designing intervention programs grounded in theories of behavior change and developing testable hypotheses related to theoretical mechanisms of change are important next steps.

Evaluating the impact of a new educational tool on understanding of polygenic risk scores for alcohol use disorder.

Introduction: As gene identification efforts have advanced in psychiatry, so have aspirations to use genome-wide polygenic information for prevention and intervention. Although polygenic risk scores (PRS) for substance use and psychiatric outcomes are not yet available in clinical settings, individuals can access their PRS through online direct-to-consumer resources. One of these widely used websites reports that alcohol use disorder is the third most requested PRS out of >1,000 conditions. However, data indicate that there are misunderstandings about complex genetic concepts, with a lower understanding of PRS being associated with a more negative impact of receiving polygenic risk information. There is a need to develop and evaluate educational tools to increase understanding of PRS. Methods: We conducted a randomized controlled trial to evaluate the impact of web-based educational information on understanding of PRS for alcohol use disorder. A total of 325 college students (70.4% female; 43.6% White; mean age = 18.9 years) from an urban, diverse university completed the study. Results: Overall, participants were highly satisfied with the educational information. Results from a one-way ANOVA indicated that there was a significant increase in overall understanding of PRS for alcohol use disorder (p-value < 0.001), among individuals who received educational information about PRS and alcohol use disorder, as compared to receiving no accompanying information (adj. p-value < 0.001), or educational information about alcohol use disorder only (adj. p-value < 0.001). Discussion: These findings suggest that the web-based educational tool could be provided alongside polygenic risk information in order to enhance understanding and interpretation of the information. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05143073].

Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

Genetically influenced externalizing and internalizing risk pathways as novel prevention targets.

Objective: Risky substance use among college students is widespread, and associated with numerous adverse consequences. Current interventions focus primarily on students' current substance use; we hypothesize that shifting focus from current use to underlying risk factors is a complementary approach that may improve effectiveness of prevention/intervention programming. This approach aligns with the personalized medicine movement, which aims to harness knowledge about underlying etiological factors to provide individuals with specific information about their unique risk profiles and personalized recommendations, to motivate and enable individuals to better self-regulate their health. Method: Our group is building and evaluating an online Personalized Feedback Program (PFP) for college students that provides feedback about the individual's underlying genetically influenced externalizing and internalizing risk factors for substance use, along with personalized recommendations/resources. The project capitalizes on work from a university-wide research project (Spit for Science; S4S), in which > 12,000 students (˜70% of 5 years of incoming freshmen) are being followed longitudinally to assess substance use and related factors across the college years. In this article, we describe our foundational work to develop the PFP. Results: From the S4S data, we have identified risk factors across four domains (Sensation Seeking, Impulsivity, Extraversion, and Neuroticism) that are correlated with college students' substance use. We developed an online self-guided PFP, in collaboration with professionals from student affairs, and using feedback from students, with the ultimate goal of conducting a randomized clinical trial. Conclusion: The provision of personalized risk information represents a novel approach to complement and extend existing college substance use programming. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction.

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates.

Interest in Genetic Feedback for Alcohol Use Disorder and Related Substance Use and Psychiatric Outcomes among Young Adults.

An exponential growing number of individuals are accessing genetic risk information via direct to consumer companies. Alcohol dependence is the third most accessed genetic risk score on a publicly available direct to consumer website. Better understanding of the degree to which individuals are interested in receiving personalized genetic feedback, the factors that relate to interest, and genetic knowledge will be critical to lay the foundation for precision medicine initiatives, especially for substance use and psychiatric outcomes, where less is known. To assess interest in receiving genetic feedback for alcohol use disorder (AUD) and understanding of genetic concepts related to psychiatric conditions, we conducted a survey with participants recruited from a registry that enrolled incoming cohorts of freshmen at an urban public university; 205 participants (76.5% female; 58.9% self-reported as White; Mage = 24.48 years) completed the survey. Results indicated that participants are highly interested in receiving genetic feedback for AUD (79.0%) but there is a lack of understanding of complex genetic concepts in a sizable proportion of the sample (25.4%). Additional research is needed to assess how to address this lack of knowledge before genetic feedback for AUD can be returned in a way that benefits the individual.

Genetic feedback for psychiatric conditions: Where are we now and where are we going.

Genome-wide association studies are rapidly advancing our understanding of the genetic architecture of complex disorders, including many psychiatric conditions such as major depression, schizophrenia, and substance use disorders. One common goal of genome-wide association studies is to use findings for enhanced clinical prediction in the future, which can aid in identifying at-risk individuals to enable more effective prevention screening and treatment strategies. In order to achieve this goal, we first need to gain a better understanding of the issues surrounding the return of complex genetic results. In this article, we summarize the current literature on: (a) genetic literacy in the general population, (b) the public's interest in receiving genetic test results for psychiatric conditions, (c) how individuals react to and interpret their genotypic information for specific psychiatric conditions, and (d) gaps in our knowledge that will be critical to address as we move toward returning genotypic information for psychiatric conditions in both research and clinical settings. By reviewing extant studies, we aim to increase awareness of the potential benefits and consequences of returning genotypic information for psychiatric conditions.