Examining Genetically-Informed Etiologic Models of Co-Occurring Posttraumatic Stress Disorder and Recreational Cannabis Use among College Students

The college years encompass a period of increased risk recreational cannabis use (RCU), as well as a time of increased risk for trauma exposure and developing posttraumatic stress disorder (PTSD). Given the high co-occurrence between RCU and PTSD, and the potentially negative consequences of the two (e.g., worse academic outcomes), there is a need to understand the etiologic mechanisms of these commonly co-occurring conditions. Two primary phenotypic models exist: self-medication model (i.e., PTSD to RCU) and the high-risk model (i.e., RCU to PTSD). To date, there are two existing studies longitudinally examining the etiologic models proposed to explain co-occurring RCU and PTSD in a college sample, but they are limited to only investigating the first two years of college. Thus, Aim 1 of this study examined these models of co-occurrence in a large, ongoing longitudinal study of college students (Spit for Science [S4S]; NIAAA-R37 AA011408, PIs Kenneth Kendler & Danielle Dick) throughout the first three years of college. Cannabis use and PTSD have been shown to be moderately heritable in twin studies. Thus, Aim 2 conducted aggregate genome-wide analyses (i.e., genome-wide complex trait analysis [GCTA], polygenic risk scores [PRS]) of RCU and PTSD to examine their molecular heritability, as well as the association of aggregate genetic risk with RCU and PTSD. Given evidence of latent heritability, as well as overlapping latent heritability of lifetime cannabis use and PTSD, examination of molecular genetic risk is also needed. Thus, Aim 3 further examined the self-medication and high-risk models by incorporating PRS for lifetime cannabis use and lifetime PTSD as potential influences of same- and cross-phenotype prediction (e.g., PRS for lifetime cannabis use predicting RCU and PTSD in S4S). To limit genetic heterogeneity, study participants were limited to individuals in S4S with European- (n = 3721) and African- (n = 1469) ancestry based off of their genomic super-population assignment. Aim 1 results supported both the self-medication and high-risk model. Aim 2 results did not provide support for significant molecular heritability of RCU or TRD in individuals with European or African ancestry in S4S likely due to low statistical power. Aim 2 results did provide evidence of same-trait prediction of PRS for lifetime cannabis use predicting non-experimental (i.e., use ≥ 6 times) cannabis use in individuals with European ancestry in S4S. Aim 3 results did not provide support for significant moderation of PRS for lifetime cannabis use or PRS for lifetime PTSD in the self-medication or high-risk models, respectively. However, Aim 3 results did provide evidence of same-trait prediction of non-experimental cannabis use based on PRS for lifetime cannabis use. Given the relatively small sample size, genotypic results should be interpreted with caution. However, as a whole, these findings provide support for the self-medication and high-risk models explaining the development of co-occurring PTSD and cannabis use. Implications of these findings, in light of study limitations, are discussed

A Longitudinal Investigation of Interpersonal Trauma Exposure, Posttraumatic Stress Disorder, and Cannabis Use Phenotypes among College Students

College students have an increased risk for cannabis use, trauma exposure, and posttraumatic stress disorder (PTSD). Cannabis use disorder (CUD) and PTSD comorbidity is high, and given the negative consequences of the comorbidity (e.g., poor academic outcomes), there is a need to understand comorbid CUD-PTSD etiology. Two primary etiologic models exist: self-medication (i.e., PTSD à CUD) and high-risk (i.e., CUD à PTSD) hypotheses. This study 1) examined the prevalence and predictors of cannabis use and interpersonal trauma (IPT) exposure; 2) investigated the relationship between cannabis use and IPT; and 3) examined cannabis use, IPT, and PTSD through mediational self-medication and high-risk hypotheses lenses in a large (n = 9,889) longitudinal study of college students. Aim 1 found the prevalence of lifetime problematic (i.e., use ≥ 6 times) and experimental (i.e., use 1-5 times) cannabis use was 28.3% and 17.4%, respectively. Aim 1 results also estimated that the prevalence of lifetime IPT exposure was 35.9%. Aim 2 results supported the self-medication hypothesis, but not the high-risk hypothesis. Overall model fit from Aim 3 was poor. Nonetheless, Aim 3 results did not support the self-medication or high-risk hypotheses. Given the poor model fit of Aim 3, results should be interpreted with caution. However, as a whole, these findings provide preliminary support for the self-medication hypothesis, indicating that those reporting IPT exposure and probable PTSD may be at risk for cannabis use. Implications of these findings, in light of study limitations, are discussed

Computerized clinical decision support systems for drug prescribing and management: A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Computerized clinical decision support systems (CCDSSs) for drug therapy management are designed to promote safe and effective medication use. Evidence documenting the effectiveness of CCDSSs for improving drug therapy is necessary for informed adoption decisions. The objective of this review was to systematically review randomized controlled trials assessing the effects of CCDSSs for drug therapy management on process of care and patient outcomes. We also sought to identify system and study characteristics that predicted benefit.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We updated our earlier reviews (1998, 2005) by searching MEDLINE, EMBASE, EBM Reviews, Inspec, and other databases, and consulting reference lists through January 2010. Authors of 82% of included studies confirmed or supplemented extracted data. We included only randomized controlled trials that evaluated the effect on process of care or patient outcomes of a CCDSS for drug therapy management compared to care provided without a CCDSS. A study was considered to have a positive effect (<it>i.e.</it>, CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive.</p> <p>Results</p> <p>Sixty-five studies met our inclusion criteria, including 41 new studies since our previous review. Methodological quality was generally high and unchanged with time. CCDSSs improved process of care performance in 37 of the 59 studies assessing this type of outcome (64%, 57% of all studies). Twenty-nine trials assessed patient outcomes, of which six trials (21%, 9% of all trials) reported improvements.</p> <p>Conclusions</p> <p>CCDSSs inconsistently improved process of care measures and seldomly improved patient outcomes. Lack of clear patient benefit and lack of data on harms and costs preclude a recommendation to adopt CCDSSs for drug therapy management.</p

The Impact of World Assumptions on the Association between Discrimination and Internalizing and Substance Use Outcomes

This study investigated whether core beliefs about the world being safe and predictable (i.e. world assumptions) mediated the association between discrimination and internalizing and substance use problems among individuals from marginalized groups. Path analyses tested mediating effects of four types of world assumptions on the association between discrimination (race-, gender-, and sexual orientation-based) and anxiety, depression, alcohol and cannabis problems in college students (N = 1,181, agemean = 19.50, SD = 1.67). Limited support for mediation by world assumptions was found: among Asian students, race-based discrimination indirectly impacted anxiety symptoms through low perceived controllability of events. Direct effects across groups and discrimination types were also found

Measurement Invariance of the World Assumptions Questionnaire across Race/Ethnic Group, Sex, and Sexual Orientation

Objective: The World Assumptions Questionnaire (WAQ) was developed to assess optimism and assumptions about the world, which often shift after traumatic events. However, no known study has investigated whether the WAQ holds similar meaning across demographic groups. The objective of this study was to investigate measurement invariance of the WAQ across race/ethnic group, sex, and sexual orientation. Method: Participants consisted of 1,181 college students (75% female; 25% Black, 13% Latinx, 18% Asian, 45% White; 90% heterosexual) who completed an online survey on stress, personality, substance use, and mental health. We investigated a unidimensional and the 4-factor structure of the WAQ using confirmatory factor analysis, and configural, metric, and scalar invariance using multigroup confirmatory factor analysis. Results: After dropping 3 items, a 4-factor structure fit the data well (comparative fit index = .92; root mean square error of approximation =.05; 95% confidence interval [.045, .054]; standardized root mean square residual = .06). Mean WAQ scores were higher for participants with probable posttraumatic stress disorder on 2 of the 4 factors. We also identified multiple items that were not invariant across race/ethnic group, sex, and sexual orientation. However, after invariant items were removed, evidence of configural, scalar, and metric invariance was found. Conclusions: This study replicated the 4-factor structure, mapping onto the 4 WAQ subscales, and indicated that a unidimensional measure of world assumptions should not be used. After making the adjustments recommended herein, the WAQ can be used to investigate differences across race/ethnic group, sex, and sexual orientation

The Associations of Racial Discrimination and Neighborhood Disadvantage With World Assumptions Among Black, Latine, and Asian Young Adults

The theory of shattered assumptions proposes that experiencing traumatic events can change how people view themselves and the world. Most adults experience a traumatic event during their lifetime, and some subsequently develop post-traumatic stress disorder (PTSD). However, the current conceptualization of trauma (i.e., Criterion A PTSD) may be too narrow to adequately capture the range of potentially traumatizing events that People of Color experience, including racial discrimination and neighborhood disadvantage. This study investigated the association of racial discrimination and neighborhood disadvantage with core beliefs about the world being safe and predictable (i.e., world assumptions) among a sample of Black, Latine, and Asian young adults. Multi-step analyses of covariance tested associations between racial discrimination and neighborhood disadvantage with world assumptions and whether these held in the context of other traumatic exposures. Results indicated that racial discrimination negatively impacted world assumptions among Asian young adults only and this effect remained in the context of trauma. In addition, low neighborhood support negatively impacted world assumptions across all racial groups and neighborhood violence negatively impacted world assumptions among Latine young adults only; however, this effect did not remain in the context of trauma. This study indicates it is worthwhile to consider other adverse events in the conceptualization of trauma, such as racial discrimination and neighborhood disadvantage, that may impact world assumptions and contribute to subsequent post-trauma psychopathology