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.

Alcohol use polygenic risk score, social support, and alcohol use among European American and African American adults.

Alcohol use is influenced by genetic and environmental factors. We examined the interactive effects between genome-wide polygenic risk scores for alcohol use (alc-PRS) and social support in relation to alcohol use among European American (EA) and African American (AA) adults across sex and developmental stages (emerging adulthood, young adulthood, and middle adulthood). Data were drawn from 4,011 EA and 1,274 AA adults from the Collaborative Study on the Genetics of Alcoholism who were between ages 18-65 and had ever used alcohol. Participants completed the Semi-Structured Assessment for the Genetics of Alcoholism and provided saliva or blood samples for genotyping. Results indicated that social support from friends, but not family, moderated the association between alc-PRS and alcohol use among EAs and AAs (only in middle adulthood for AAs); alc-PRS was associated with higher levels of alcohol use when friend support was low, but not when friend support was high. Associations were similar across sex but differed across developmental stages. Findings support the important role of social support from friends in buffering genetic risk for alcohol use among EA and AA adults and highlight the need to consider developmental changes in the role of social support in relation to alcohol use.

Social processes during recovery: An expansion of Kelly and Hoeppner's biaxial formulation of recovery.

Recent conceptualizations frame addiction recovery as a complex process involving changes across behavioral, physical, psychological, and social domains. These broad conceptualizations can be difficult to apply directly to research, making detailed models of individual dimensions necessary to guide empirical work and subsequent clinical interventions. We used Kelly and Hoeppner's (2015) biaxial formulation of recovery as a basis for a detailed examination of social processes in recovery using social network approaches. We delineated how appraisal of situational risks and social network resources result in coping actions, and how repeated iterations of this process change a person's social recovery capital over time. In addition, we incorporated the experience of interpersonal trauma and structural oppression, and demonstrated how the model accommodates the complex issues often encountered during recovery. We present a measurable framework that can guide empirical testing of how social processes and social recovery capital change over time during recovery. The model presented here illuminates key factors in the recovery process that have the potential to support trauma- and social-network-informed interventions. We call for research that empirically tests this model in ways that will result in practical, trauma-informed social network interventions for people in recovery.

Alcohol use disorder conceptualizations and diagnoses reflect their sociopolitical context.

The present paper highlights how alcohol use disorder (AUD) conceptualizations and resulting diagnostic criteria have evolved over time in correspondence with interconnected sociopolitical influences in the United States. We highlight four illustrative examples of how DSM-defined alcoholism, abuse/dependence, and AUD have been influenced by sociopolitical factors. In doing so, we emphasize the importance of recognizing and understanding such sociopolitical factors in the application of AUD diagnoses. Last, we offer a roadmap to direct the process of future efforts toward the improved diagnosis of AUD, with an emphasis on pursuing falsifiability, acknowledging researchers' assumptions about human behavior, and collaborating across subfields. Such efforts that center the numerous mechanisms and functions of behavior, rather than signs or symptoms, have the potential to minimize sociopolitical influences in the development of diagnostic criteria and maximize the treatment utility of diagnoses.

Evaluating risk for alcohol use disorder: Polygenic risk scores and family history.

BACKGROUND: Early identification of individuals at high risk for alcohol use disorder (AUD) coupled with prompt interventions could reduce the incidence of AUD. In this study, we investigated whether Polygenic Risk Scores (PRS) can be used to evaluate the risk for AUD and AUD severity (as measured by the number of DSM-5 AUD diagnostic criteria met) and compared their performance with a measure of family history of AUD. METHODS: We studied individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA). DSM-5 diagnostic criteria were available for 7203 individuals, of whom 3451 met criteria for DSM-IV alcohol dependence or DSM-5 AUD and 1616 were alcohol-exposed controls aged ≥21 years with no history of AUD or drug dependence. Further, 4842 individuals had a positive first-degree family history of AUD (FH+), 2722 had an unknown family history (FH?), and 336 had a negative family history (FH-). PRS were derived from a meta-analysis of a genome-wide association study of AUD from the Million Veteran Program and scores from the problem subscale of the Alcohol Use Disorders Identification Test in the UK Biobank. We used mixed models to test the association between PRS and risk for AUD and AUD severity. RESULTS: AUD cases had higher PRS than controls with PRS increasing as the number of DSM-5 diagnostic criteria increased (p-values ≤ 1.85E-05 ) in the full COGA sample, the FH+ subsample, and the FH? subsample. Individuals in the top decile of PRS had odds ratios (OR) for developing AUD of 1.96 (95% CI: 1.54 to 2.51, p-value = 7.57E-08 ) and 1.86 (95% CI: 1.35 to 2.56, p-value = 1.32E-04 ) in the full sample and the FH+ subsample, respectively. These values are comparable to previously reported ORs for a first-degree family history (1.91 to 2.38) estimated from national surveys. PRS were also significantly associated with the DSM-5 AUD diagnostic criterion count in the full sample, the FH+ subsample, and the FH? subsample (p-values ≤6.7E-11 ). PRS remained significantly associated with AUD and AUD severity after accounting for a family history of AUD (p-values ≤6.8E-10 ). CONCLUSIONS: Both PRS and family history were associated with AUD and AUD severity, indicating that these risk measures assess distinct aspects of liability to AUD traits.

Deriving a Measure of Social Recovery Capital From the Important People and Activities Instrument: Construction and Psychometric Properties.

AIM: This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). METHODS: The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. RESULTS: Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald's ω = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. CONCLUSION: The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.

Opportunities to improve sleep of children exposed to interpersonal violence: A social-ecological perspective.

Over 25% of U.S. children are witness to traumatic intrafamilial or community violence each year, and sleep medicine and developmental research jointly suggest that trauma-exposed youth experience more sleep disturbance than their non-exposed counterparts. Sleep medicine literature emphasizes physical and social environmental factors affecting sleep, and trauma literature underscores children's seeking out physically and emotionally safe and predictable environments during trauma recovery. This study employed a hermeneutic phenomenological framing to explore the lived experiences of 65 violence-exposed children and families, and to examine how youths' social and physical sleep environments facilitated or impeded sleep in the aftermath of trauma. Children's sleep experiences following violence exposure shared two primary essences of experience: a) navigating external threats that agitated sleep after trauma; and b) exercising agency over sleep and related environments to restabilize emotional security. Clinicians and social services coordinators working with children and families are uniquely positioned to indicate sleep assessments as part of treatment following trauma, and to also facilitate identification of tangible, sleep-supportive and changeable factors in sleep environments.

Characterization of Service Use for Alcohol Problems Across Generations and Sex in Adults With Alcohol Use Disorder.

BACKGROUND: There are gaps in the literature on service use (help-seeking and treatment utilization) for alcohol problems among those with alcohol use disorder (AUD). First, policy changes and cultural shifts (e.g., insurance) related to AUD have occurred over the last few decades, making it important to study generational differences. Second, multiple studies have found that females receive fewer services than males, and exploring whether these sex differences persist across generations can inform public health and research endeavors. The current study examined service use for alcohol problems among individuals with AUD. The aims were as follows: (i) to describe service use for alcohol problems; (ii) to assess generational differences (silent [b. 1928 to 1945], boomer [b. 1946 to 1964], generation X [b. 1965 to 1980], millennial [b. 1981 to 1996]) in help-seeking and treatment utilization; and (iii) to examine sex differences across generations. METHODS: Data were from affected family members of probands who participated in the Collaborative Study on the Genetics of Alcoholism (N = 4,405). First, frequencies for service use variables were calculated across generations. Pearson chi-square and ANOVA were used to test for differences in rates and types of service use across generations, taking familial clustering into account. Next, Cox survival modeling was used to assess associations of generation and sex with time to first help-seeking and first treatment for AUD, and time from first onset of AUD to first help-seeking and first treatment. Interactions between generation and sex were tested within each Cox regression. RESULTS: Significant hazards were found in all 4 transitions. Overall, younger generations used services earlier than older generations, which translated into higher likelihoods of these behaviors. Regardless of generation, younger females were less likely to use services than males. CONCLUSIONS: There are generational and sex differences in service use for alcohol problems among individuals with AUD. Policy and clinical implications are discussed.

Transitions of Women's Substance Use Recovery Networks and 12-Month Sobriety Outcomes.

Little is known about how the structure and composition of women's personal social networks (PSNs) combine to support recovery from substance use disorders, how PSNs change during early recovery, or how known covariates such as trauma, co-occurring mental health disorders, or treatment modality impact this relationship. This study used latent profile and transition analyses with 6 recovery-specific PSN indicators in a sample of women in early recovery (N=377) to identify three PSN typologies in relation to abstinence outcomes over 12 months, and track transitions between the typologies at 0-6 and 6-12 months. Women in the Highly Connected type (14.3%) had tightly-knit networks, more sober alters, and fewer treatment-related alters. Women in the Treatment-Related type (49.3%) had looser-knit networks with more sober and sobriety-supporting alters and alters they know from treatment. Women in the At-Risk type (36.3%) had more isolates, few sobriety-supporting alters, and more alters with whom they used. Women in the Treatment-Related Sobriety Support type were significantly more likely to maintain sobriety by 12 months (B=-0.81; OR=2.09, 95% CI [1.23-3.56]) than women in the At Risk type. Higher mean Trauma Symptom Checklist scores were positively related to membership in the At Risk type. The majority of women who transitioned did so by 6 months, with 41.6% transitioning then. Women in the At Risk group had the highest probability of transition (P=0.55). Being in residential treatment (versus outpatient) predicted lower odds of transitioning (B= -0.81, p=.06). This study provides a framework for conducting longitudinal latent variable analysis with social network data, and offers a clinically-useful starting point for research on individualized, targeted, and stage-based interventions for women in recovery.

Choose who's in your circle: how women's relationship actions during and following residential treatment help create recovery-oriented networks.

Women in recovery from substance use disorders often have difficulty establishing recovery-supportive networks. This exploratory study uses qualitative thematic analysis to examine how 88 women in recovery describe the actions they take to manage their personal social networks 12 months after intake into residential substance use treatment. Participants describe disconnecting or limiting contact with recovery-endangering people and adding recovery-supportive people to their networks as primary relationship actions for maintaining recovery. Their actions to build recovery-supportive networks can provide a focus for clinical work to help them become integrated into their communities.

Factor Structure of the Urban Hassles Index.

OBJECTIVE: This study examined the factor structure and psychometric properties of the Urban Hassles Index (UHI). METHODS: Exploratory factor analyses (EFA) were conducted via Principal Axis Factoring extraction method. Confirmatory factor analyses were conducted to evaluate the fit of the EFA-derived model using the weighted least squares estimator with mean and variance adjustments. Composite/scale scores were created for the extracted factors, with a total score derived by summing the scale scores. Criterion-related validity was examined using hierarchical regressions. RESULTS: The UHI had four first-order factors (Environmental Nuisance, Safety Concerns, Drug, Coercion) accounting for 43% of the total variance. Covariance among the first-order factors was explained by a higher second-order factor. Moderate factor correlations and evidence for the criterion-related validity of the subscales and total score indicated multidimensionality of the UHI. CONCLUSIONS: The shortened 16-item UHI is a brief assessment tool evaluating stressors unique to urban adolescents, providing specific intervention targets.

Associations between alcohol use disorder polygenic score and remission in participants from high-risk families and the Indiana Biobank.

BACKGROUND: In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGSAUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGSAUD would be negatively associated with remission. METHODS: Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history. RESULTS: In COGA EA, PGSAUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, ßs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGSAUD was positively associated with remission (p = 0.004, ß = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, ß = 0.15). CONCLUSIONS: PGSAUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.

The collaborative study on the genetics of alcoholism: Sample and clinical data.

The collaborative study on the genetics of alcoholism (COGA) is a multi-site, multidisciplinary project with the goal of identifying how genes are involved in alcohol use disorder and related outcomes, and characterizing how genetic risk unfolds across development and in conjunction with the environment and brain function. COGA is a multi-generational family-based study in which probands were recruited through alcohol treatment centers, along with a set of community comparison families. Nearly 18,000 individuals from >2200 families have been assessed over a period of over 30 years with a rich phenotypic battery that includes semi-structured psychiatric interviews and questionnaire measures, along with DNA collection and electrophysiological data on a large subset. Participants range in age from 7 to 97, with many having longitudinal assessments, providing a valuable opportunity to study alcohol use and problems across the lifespan. Here we provide an overview of data collection methods for the COGA sample, and details about sample characteristics and comorbidity. We also review key research findings that have emerged from analyses of the COGA data. COGA data are available broadly to researchers, and we hope this overview will encourage further collaboration and use of these data to advance the field.

Changes over time in endorsement of 11 DSM-IV alcohol use disorder (AUD) criteria in young adults with persistent or recurrent AUD in The Collaborative Study on the Genetics of Alcoholism.

BACKGROUND: Endorsement of specific Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) alcohol use disorder (AUD) criteria have been shown to change significantly over time in men in their thirties who have persistent or recurrent AUD. However, few studies have documented whether the endorsement of AUD items changes over time in younger individuals or in women. We evaluated changes in the endorsement of AUD criteria in 377 men and women with persistent or recurrent AUD during their twenties. METHODS: Information on AUD-item endorsement over time was available for 223 men and 154 women aged 20-25 with persistent or recurrent AUD in at least three interviews in the Collaborative Study on the Genetics of Alcoholism. The statistical significance of endorsement changes over time was evaluated using the related-sample Cochran's Q test for the full sample and for men and women separately. Additional analyses evaluated sex differences in the patterns of change. RESULTS: In the full sample, the predominant pattern was for a significant increase in the rates of endorsement for six of the seven alcohol dependence criteria but not in the four abuse criteria. A similar pattern was seen within men, but women had significant changes in only three of the seven dependence criteria. CONCLUSIONS: Endorsement of the seven alcohol dependence criteria among individuals with persistent or recurrent AUD in their twenties generally increased, but few changes were observed in the rates of endorsement of the four abuse criteria. These results are discussed in terms of how they reflect on the nature of AUD and the DSM criteria.

The effect of cannabis policies on treatment outcomes for cannabis use among U.S. adults.

BACKGROUND: Research has explored the impact of various medical cannabis policies on substance use treatment admission in recent years, but we know little about factors related to participants' treatment engagement and outcome. To fill this gap in the existing literature, this study used national data to examine the influence of cannabis policies (decriminalized, medical, and recreational) and referral sources (criminal justice vs. voluntary) on treatment completion and length of stay. METHODS: Data came from the Treatment Episode Data Set-Discharge (2006-2017) on adults 18+ whose primary drug at treatment admission was cannabis. Difference-in-difference analyses using logistic regression examined the effect of cannabis policies on outpatient treatment completion (yes/no; n = 2,192,807) and length of stay (more/fewer than 90 days; n = 1,863,585) in those with a criminal justice or voluntary referral source. RESULTS: Cannabis policy was not associated with treatment completion in either those with a criminal justice or voluntary referral source. Compared to individuals in states where cannabis use was strictly illegal, those in states with a decriminalization policy were less likely to stay in treatment for 91+ days regardless of the referral source. CONCLUSIONS: Cannabis policy appears to have a differential effect on treatment completion versus length of stay, with policy having no impact on successful treatment completion. Specifically, we found that decriminalization policies hinder treatment engagement past 90 days. In this sense, length of stay may be a more useful measure of treatment outcome for research than treatment completion moving forward. Furthermore, our study found that neither medical nor recreational policies affected length of stay or treatment completion, regardless of referral source.

Predicting alcohol use disorder remission: a longitudinal multimodal multi-featured machine learning approach.

Predictive models for recovering from alcohol use disorder (AUD) and identifying related predisposition biomarkers can have a tremendous impact on addiction treatment outcomes and cost reduction. Our sample (N = 1376) included individuals of European (EA) and African (AA) ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA) who were initially assessed as having AUD (DSM-5) and reassessed years later as either having AUD or in remission. To predict this difference in AUD recovery status, we analyzed the initial data using multimodal, multi-features machine learning applications including EEG source-level functional brain connectivity, Polygenic Risk Scores (PRS), medications, and demographic information. Sex and ancestry age-matched stratified analyses were performed with supervised linear Support Vector Machine application and were calculated twice, once when the ancestry was defined by self-report and once defined by genetic data. Multifeatured prediction models achieved higher accuracy scores than models based on a single domain and higher scores in male models when the ancestry was based on genetic data. The AA male group model with PRS, EEG functional connectivity, marital and employment status features achieved the highest accuracy of 86.04%. Several discriminative features were identified, including collections of PRS related to neuroticism, depression, aggression, years of education, and alcohol consumption phenotypes. Other discriminated features included being married, employed, medication, lower default mode network and fusiform connectivity, and higher insula connectivity. Results highlight the importance of increasing genetic homogeneity of analyzed groups, identifying sex, and ancestry-specific features to increase prediction scores revealing biomarkers related to AUD remission.

The association of prenatal cocaine exposure, externalizing behavior and adolescent substance use.

Prenatal cocaine exposure (PCE) may increase adolescent substance use through alterations of neurotransmitter systems affecting fetal brain development. The relationship between PCE and substance use at 15 and 17 years was examined. Subjects (365: 186 PCE; 179 non-cocaine exposed (NCE)) supplied biologic and self-report data using the Youth Risk Behavior Surveillance System (YRBSS) and Computerized Diagnostic Interview Schedule for Children (C-DISC 4) at ages 15 and 17. The relationship between PCE and substance use was assessed using General Estimating Equation (GEE) analyses controlling for confounding factors including violence exposure and preschool lead level. Teens with PCE vs. NCE teens were 2 times more likely to use tobacco (OR=2.1; 95% CI 1.21-3.63; p<.001) and marijuana (OR=1.85; CI 1.18-2.91; p<.001) and have a substance use disorder at age 17 (OR=2.51; CI 1.00-6.28; p<.05). Evaluation of PCE status by gender revealed an association between PCE and marijuana use that was more pronounced for boys than girls at 17 years. Violence exposure was also a significant predictor of alcohol (p<.001), tobacco (p<.05), and marijuana (p<.0006) use and substance abuse/dependence (p<.01). Externalizing behavior at age 12 fully mediated the effects of PCE on substance use disorder at age 17 and partially mediated effects of PCE on tobacco use, but did not mediate effects on marijuana use. The percentage of substance use reported increased between 15 and 17 years, with no differences between the PCE and NCE groups. Data suggest specialized drug use prevention measures for children with PCE may benefit this high risk group.

Personal Network Structure and Substance Use in Women by 12 Months Post Treatment Intake.

INTRODUCTION: Women with substance use disorders enter treatment with limited personal network resources and reduced recovery support. This study examined the impact of personal networks on substance use by 12 months post treatment intake. METHODS: Data were collected from 284 women who received substance abuse treatment. At 6 month follow up, composition, support availability and structure of personal networks were examined. Substance use was measured by women's report of any use of alcohol or drugs. Hierarchical multivariate logistic regression was conducted to examine the contribution of personal network characteristics on substance use by 12 months post treatment intake. RESULTS: Higher numbers of substance using alters (network members) and more densely connected networks at 6 month follow-up were associated with an increased likelihood of substance use by 12 months post treatment intake. A greater number of isolates in women's networks was associated with decreased odds of substance use. Women who did not use substances by 12 months post treatment intake had more non-users among their isolates at 6 months compared to those who used substances. No association was found between support availability and likelihood of substance use. CONCLUSIONS: Both network composition and structure could be relevant foci for network interventions e.g. helping women change network composition by reducing substance users as well as increasing network connections. Isolates who are not substance users may be a particular strength to help women cultivate within their network to promote sustained sobriety post treatment.