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Background: The COVID-19 pandemic was managed in part by the rapid development of vaccines, diagnostics, and therapeutics including antiviral agents and advances in emergency airway and ventilatory management. The impact of these therapeutic advances on clinically pertinent metrics of emergency care have not been well-studied., Methods: We abstracted data from emergency department (ED) visits made to 21 US health systems during the first two years of the pandemic, from February 1, 2020 to January 31, 2022. These health systems were participants in the NIH-supported COVID EHR Cohort, in which the University of Wisconsin served as the coordinating site. Limited patient-level data files were submitted monthly. Data elements included demographic and clinical variables, as well as standard measures of ED outcomes including 72-h returns, 72-h returns leading to readmission, and in-hospital mortality. Multivariable models were fitted to identify correlates of each of the dependent variables. A test for trend was used to detect changes in outcomes over time., Results: During the two-year period, 150,357 individuals aged 18 years or older visited the ED. The median age was 45.4 years (IQR 27), 58.1 % were female, 49 % were White, 18.3 % Hispanic/Latino, and 45 % were publicly insured or uninsured. The prevalence of 72-h ED returns, readmissions, and in-hospital mortality significantly declined across the two-year period. SARS-CoV-2 vaccination was associated with reduced ED returns and mortality. Therapeutic agents were associated with increased mortality risk but were likely confounded by unmeasured covariates., Conclusions: Operational and clinical outcomes of ED-based treatment of individuals with COVID-19 improved in the first two years of the pandemic. This improvement is likely multifactorial and includes the development and deployment of SARS-CoV-2-specific vaccines, therapeutic agents, and improved healthcare delivery in the ED and elsewhere addressing management of airway and ventilatory status, as well as increased innate immunity in the general population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: COVID-19 had devastating impacts worldwide. However, most research examining the impact of dementia on COVID-19 outcomes has been conducted in Europe and Asia and has not examined dementia subtypes., Methods: A retrospective analysis of electronic health record data from 21 US health-care systems examined relationships of all-cause dementia, Alzheimer's disease (AD), and vascular dementia with in-hospital mortality, intensive care unit (ICU) admission, and hospital stay duration., Results: All-cause dementia, but not AD or vascular dementia independently, was associated with increased mortality risk, the inclusion of discharge to hospice as a mortality equivalent increased risk for mortality for all-cause dementia, and AD and vascular dementia. Patients with all-cause dementia and AD were less likely to be admitted to the ICU than patients without. Patients with any form of dementia had longer hospital stays than patients without., Discussion: Dementia was associated with increased mortality or hospice discharge, decreased ICU admissions, and longer hospital stays., Highlights: Only all-cause dementia was associated with increased mortality risk. This risk was lower than what has been published in previous research. Combining mortality and hospice discharge increased risk for all dementia subtypes. All-cause and Alzheimer's disease (AD) dementia were associated with decreased intensive care unit admissions. All-cause, vascular, and AD dementia were associated with longer hospital stays., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Older adults are at higher risk of severe outcomes from COVID-19 with comorbidities increasing such risk. Much less is known about the outcomes of young adults with COVID-19 despite their having had high infection rates., Objectives: Our objective was to determine outcomes of hospitalized young adults with COVID-19 infection including rates of oxygen use, mortality, ICU admission, intubation, duration of hospitalization, and factors associated with adverse outcomes., Study Design: This retrospective cohort study included EHR data from 21 health systems in the United States on 18-29-year-olds hospitalized with COVID-19 from March 1, 2020 - January 31, 2022. Oxygen need was used to identify symptomatic COVID-19. Rates for mortality, ICU admission, and intubation were calculated for the symptomatic and asymptomatic groups. Effects of demographic and health characteristics on outcomes were assessed as were changes in hospital outcomes over time., Results: Our sample included 9871 young adults hospitalized with COVID-19; 35% required oxygen. Of those who required oxygen, 53.5% were female, 23.7% had an anxiety disorder, 2.6% died ( n  = 89), 27.7% were admitted to the ICU ( n  = 955), and 15.8% were intubated ( n  = 547). A past-year history of any cancer was associated with a 2.1 times increased odds of death. Vaccination was associated with a >40% reduction in the odds of ICU admission. Mortality rates did not change significantly across the study period., Conclusions: COVID-19 caused significant morbidity and mortality in hospitalized young adults who required oxygen. A cancer history was associated with increased risk of death. Vaccination appeared to have had a protective effect on illness severity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Patterns of association with externalizing and internalizing features differ across heroin use and prescription opioid misuse (POM). The present study examined whether heroin use and POM display differential etiologic overlap with symptoms of conduct disorder (CD), adult antisocial behavior (AAB), and major depressive episodes (MDEs), how aggregating heroin use and POM into a single phenotype may bias results, and explored potential sex differences. Seven thousand one hundred and sixty-four individual twins from the Australian Twin Registry (ATR; 59.81% female; M age = 30.58 years) reported lifetime heroin use, POM, CD symptoms, AABs, and MDE symptoms within a semi-structured interview. Biometric models decomposed phenotypic variance and covariance into additive genetic, common environmental, and unique environmental effects. The proportion of variance in heroin use attributable to factors shared with CD, AAB, and MDE, respectively, was 41%, 41%, and 0% for men and 26%, 19%, and 42% for women; for POM, the proportions were 33%, 35%, and 20% for men and 15%, 9%, and 13% for women. CD and AAB were more strongly genetically correlated with heroin use among women and with POM among men. MDE was more strongly genetically correlated with POM than with heroin use among men, but more strongly genetically correlated with heroin use than with POM among women. Analyses using an aggregate opioid (mis)use variable were biased toward POM, which was the more prevalent phenotype. Magnitude and source of etiologic influence may differ across forms of opioid (mis)use and sex. Disaggregating heroin use and POM in future opioid research may be warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objective: A propensity for aggression or alcohol use may be associated with alcohol-related aggression. Previous research has shown genetic overlap between alcohol use and aggression but has not looked at how alcohol-related aggression may be uniquely influenced by genetic risk for aggression or alcohol use. The present study examined the associations of genetic risk for trait aggression, alcohol use, and alcohol use disorder (AUD) with alcohol-related aggression using a polygenic risk score (PRS) approach., Method: Using genome-wide association study summary statistics, PRSs were created for trait aggression, alcohol consumption, and AUD. These PRSs were used to predict the phenotype of alcohol-related aggression among drinkers in two independent samples: the University of California at San Francisco (UCSF) Family Alcoholism Study ( n = 1,162) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 4,291)., Results: There were significant associations between the AUD PRS and lifetime alcohol-related aggression in the UCSF study sample. Additionally, the trait aggression PRS was associated with three or more experiences of hitting anyone else and getting into physical fights while under the influence of alcohol, along with a composite score of three or more experiences of alcohol-related aggression, in the UCSF study sample. No significant associations were observed in the Add Health sample. Limited sex-specific genetic effects were observed., Conclusions: These results provide preliminary evidence that genetic influences underlying alcohol use and aggression are uniquely associated with alcohol-related aggression and suggest that these associations may differ by type and frequency of alcohol-related aggression incidents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Only a small proportion of individuals who initiate nonmedical use of prescription opioids (NUPO) transition to heroin, suggesting that more nuanced aspects of NUPO may be better indicators of risk for escalating opioid use trajectories. This study leveraged panel data to identify NUPO typologies based on NUPO characteristics associated with opioid risk trajectories (route of administration, motives) and compared rates of heroin initiation at follow-up across typologies., Methods: Latent class analyses were run among respondents with no history of heroin use from the Monitoring the Future Panel Study (base year N=10,408) at modal ages 18, 19/20, 21/22, 23/24, and 25/26. Indicators included oral NUPO, nonoral NUPO, and NUPO motives to experiment, have a good time with friends, get high, escape problems, manage pain, relax, and sleep. Heroin initiation at follow-ups through modal age 29/30 was predicted from class membership., Results: No NUPO, self-medication (oral, manage pain), recreational (oral, nonoral, experiment, get high, have a good time with friends), and mixed-motive (all routes, all motives) classes emerged. Heroin initiation rates did not differ across no NUPO and self-medication classes; recreational and mixed-motives classes initiated heroin at higher rates than the other classes and comparable rates to each other. Non-NUPO drug use prior to heroin initiation was prevalent in recreational and mixed-motive classes., Conclusions: NUPO does not uniformly or uniquely increase risk for heroin initiation. Leveraging more nuanced indicators of risk for heroin use and targeting polysubstance use in addition to opioid-specific programming may enhance the efficacy of public health efforts., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Examine the nature of the relationship between adolescent polysubstance use and high school noncompletion., Method: Among a sample of 9,579 adult Australian twins (58.63% female, M age = 30.59), we examined the association between the number of substances used in adolescence and high school noncompletion within a discordant twin design and bivariate twin analysis., Results: In individual-level models controlling for parental education, conduct disorder symptoms, childhood major depression, sex, zygosity, and cohort, each additional substance used in adolescence was associated with a 30% increase in the odds of high school noncompletion ( OR = 1.30 [1.18, 1.42]). Discordant twin models found that the potentially causal effect of adolescent use on high school noncompletion was nonsignificant ( OR = 1.19 [0.96, 1.47]). Follow-up bivariate twin models suggested genetic (35.4%, 95% CI [24.5%, 48.7%]) and shared environmental influences (27.8%, 95% CI [12.7%, 35.1%]) each contributed to the covariation in adolescent polysubstance use and early school dropout., Conclusions: The association between polysubstance use and early school dropout was largely accounted for by genetic and shared environmental factors, with nonsignificant evidence for a potentially causal association. Future research should examine whether underlying shared risk factors reflect a general propensity for addiction, a broader externalizing liability, or a combination of the two. More evidence using finer measurement of substance use is needed to rule out a causal association between adolescent polysubstance use and high school noncompletion. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

American Indian and Alaska Native (AI/AN) individuals are more likely to die with COVID-19 than other groups, but there is limited empirical evidence to explain the cause of this inequity. The objective of this study was to determine whether medical comorbidities, area socioeconomic deprivation, or access to treatment can explain the greater COVID-19 related mortality among AI/AN individuals. The design was a retrospective cohort study of harmonized electronic health record data of all inpatients with COVID-19 from 21 United States health systems from February 2020 through January 2022. The mortality of AI/AN inpatients was compared to all Non-Hispanic White (NHW) inpatients and to a matched subsample of NHW inpatients. AI/AN inpatients were more likely to die during their hospitalization (13.2% versus 7.1%; odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.48, 2.65) than their matched NHW counterparts. After adjusting for comorbidities, area social deprivation, and access to treatment, the association between ethnicity and mortality was substantially reduced (OR 1.59, 95% CI 1.15, 2.22). The significant residual relation between AI/AN versus NHW status and mortality indicate that there are other important unmeasured factors that contribute to this inequity. This will be an important direction for future research., (© 2023. The Author(s).)

Background: Despite its introduction into the diagnostic nomenclature over four decades ago, there remain large knowledge gaps about disordered gambling. The primary aims of the present study were to document the long-term course, childhood precursors, and adult life outcomes associated with disordered gambling., Methods: Participants enrolled in the population-representative Dunedin Study were prospectively followed from birth through age 45. Disordered gambling was assessed six times from age 18; composite measures of childhood social class, general intelligence, and low self-control were based on assessments obtained from birth through age 15; adult socioeconomic, financial, and legal outcomes were obtained through age 45. Lifetime disordered gambling was predicted from the three childhood precursors and the adult outcomes were predicted from lifetime disordered gambling., Results: Past-year disordered gambling usually occurred at only a single time point and recurrence was relatively uncommon. Lower childhood social class, general intelligence, and self-control significantly predicted lifetime disordered gambling in adulthood. In turn, lifetime disordered gambling in adulthood significantly predicted occupational, educational, and financial problems in adulthood ( ds = 0.23-0.41). These associations were markedly reduced and sometimes rendered nonsignificant after adjusting for childhood precursors ( ds = 0.04-0.32)., Conclusions: Socioeconomic, financial, and legal outcomes in adulthood are not merely consequences of disordered gambling, but also are predicted from childhood precursors. Deflecting the trajectories of young people at risk for developing disordered gambling may help to ameliorate not just the development of later disordered gambling, but also other associated adverse outcomes.

Identifying patients at risk for readmission after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could facilitate care planning and prevention. This retrospective cohort study of 60-day readmission included 105 543 COVID-19 patients at 21 US healthcare systems who were discharged alive between February 2020 and November 2021. Generalized linear mixed regression analyses tested predictors of 60-day readmission and severity. The all-cause readmission rate was 15% (95% confidence interval [CI] = 10%-21%), with 22% (95% CI = 18%-26%) of readmitted patients needing intensive care, and 6% (95% CI = 05%-07%) dying. Factors associated with readmission included male sex, government insurance, positive smoking history, co-morbidity burden, longer index admissions, and diagnoses at index admission (e.g., cancer, chronic kidney disease, and liver disease). Death and intensive care rates at readmission declined postvaccine availability. Receiving at least two COVID-19 vaccine doses, which were more common among older patients and those with comorbid conditions, was not independently associated with readmission but predicted a reduced risk of death at readmission. This retrospective cohort study identified factors associated with all-cause readmission for patients re-admitted to the same health system after hospitalization with SARS-CoV-2 infection. Patients who are male, who smoke, who have a higher comorbidity burden, and have government insurance may benefit from additional postacute care planning., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Introduction: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown., Methods: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission., Results: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97)., Conclusions: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers., Implications: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: Many studies aggregate prescription opioid misuse (POM) and heroin use into a single phenotype, but emerging evidence suggests that their genetic and environmental influences may be partially distinct., Methods: In total, 7164 individual twins (84.12% complete pairs; 59.81% female; mean age = 30.58 years) from the Australian Twin Registry reported their lifetime misuse of prescription opioids, stimulants, and sedatives, and lifetime use of heroin, cannabis, cocaine/crack, illicit stimulants, hallucinogens, inhalants, solvents, and dissociatives via telephone interview. Independent pathway models (IPMs) and common pathway models (CPMs) partitioned the variance of drug use phenotypes into general and drug-specific genetic ( a ), common environmental ( c ), and unique environmental factors ( e )., Results: An IPM with one general a and one general e factor and a one-factor CPM provided comparable fit to the data. General factors accounted for 55% ( a = 14%, e = 41%) and 79% ( a = 64%, e = 15%) of the respective variation in POM and heroin use in the IPM, and 25% ( a = 12%, c = 8%, e = 5%) and 80% ( a = 38%, c = 27%, e = 15%) of the respective variation in POM and heroin use in the CPM. Across both models, POM emerged with substantial drug-specific genetic influence (26-39% of total phenotypic variance; 69-74% of genetic variance); heroin use did not (0% of total phenotypic variance; 0% of genetic variance in both models). Prescription sedative misuse also demonstrated significant drug-specific genetic variance., Conclusions: Genetic variation in POM, but not heroin use, is predominantly drug-specific. Misuse of prescription medications that reduce experiences of subjective distress may be partially influenced by sources of genetic variation separate from illicit drug use.

It is vital to determine how patient characteristics that precede COVID-19 illness relate to COVID-19 mortality. This is a retrospective cohort study of patients hospitalized with COVID-19 across 21 healthcare systems in the US. All patients (N = 145,944) had COVID-19 diagnoses and/or positive PCR tests and completed their hospital stays from February 1, 2020 through January 31, 2022. Machine learning analyses revealed that age, hypertension, insurance status, and healthcare system (hospital site) were especially predictive of mortality across the full sample. However, multiple variables were especially predictive in subgroups of patients. The nested effects of risk factors such as age, hypertension, vaccination, site, and race accounted for large differences in mortality likelihood with rates ranging from about 2-30%. Subgroups of patients are at heightened risk of COVID-19 mortality due to combinations of preadmission risk factors; a finding of potential relevance to outreach and preventive actions., (© 2023. The Author(s).)

Objective: High neuroticism, low agreeableness, and low conscientiousness are consistent correlates of drug use, though such patterns may be due to common familial influences rather than effects of personality per se. The present study aimed to explore associations of Big Five traits with various forms of drug use independent of confounding familial influences by leveraging differences within twin pairs to identify potentially causal (i.e., within-pair) effects of personality on use., Method: 980 same-sex twin pairs from the Australian Twin Registry Cohort III ( M age = 31.70, 71% female) were interviewed regarding lifetime (mis)use of cannabis, cocaine/crack, prescription and illicit stimulants, prescription and illicit opioids, sedatives, hallucinogens, dissociatives, inhalants, and solvents, and completed a Big Five inventory. Co-twin control analyses predicted the use of each drug from all traits simultaneously., Results: Individual-level analyses generally showed the expected associations of neuroticism, agreeableness, and conscientiousness with drug use. Familial effects were also somewhat generalized: high neuroticism, high openness to experience, and low agreeableness were associated with the use of several drug types. More specificity emerged for within-pair effects. High neuroticism was associated with prescription drug misuse; high extraversion was associated with cocaine/crack and stimulant use; high openness to experience was associated with cannabis use; low agreeableness was associated with cocaine/crack use and illicit opioid use; and no within-pair effects emerged for conscientiousness., Conclusions: Trait associations common across drugs may be primarily attributable to familial effects. There appears to be more drug-specific influence of personality on use with respect to potentially causal within-pair effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics., Methods: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined., Results: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46-1.70] and 1.04 (95% CI, 0.96-1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53-0.90)., Conclusions: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types., Impact: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background and Aims: Previous studies have demonstrated associations between substance use and reduced educational attainment; however, many were unable to account for potential confounding factors like genetics and the rearing environment. In the few studies that controlled for these factors, the substances assessed were limited to alcohol, cannabis, and tobacco. To address these limitations, we examined the relationship between adolescent use of seven kinds of substances, the number of additional substances used, and high school noncompletion within a large sample of Australian twins., Design: A series of two-level generalized mixed effects logistic regressions were conducted to examine associations between adolescent substance use and high school noncompletion., Setting: Australia., Participants: A total of 9579 adult Australian twins from two cohorts of the Australian Twin Registry., Measurements: Assessments of high school completion, childhood major depression, conduct disorder symptoms, substance use initiation, demographics, and parental educational attainment using the Australian version of the Semi-Structured Assessment for the Genetics of Alcoholism., Findings: There were unique within-twin-pair effects of use of sedatives (odds ratio [OR] = 22.39 [95% confidence interval (CI) = 1.18-423.48]) and inhalants/solvents (OR = 10.46 [95% CI = 1.30-84.16]) on high school noncompletion. The number of substances used in adolescence was strongly associated with high school noncompletion across all discordant twin models (ORs from 1.50-2.32, Ps < 0.03)., Conclusions: In Australia, adolescent substance use appears to be associated with early school dropout, with the effects of any given substance largely because of the confounding factors of parental education, childhood conduct disorder symptoms, and use of other substances. Sedatives and inhalants/solvents have effects on high school noncompletion that cannot be explained by polysubstance use or familial factors., (© 2022 Society for the Study of Addiction.)

Objective: The role of simultaneous alcohol and marijuana (SAM) use in the experience of blackouts among college students is unclear. To clarify discrepancies, the current study evaluated whether the association between SAM user status and blackouts was moderated by high-intensity drinking (HID). Participants and Methods: College students (N = 1,224; 63.7% female) reported on their past year experiences of blackout, marijuana use, SAM use, and HID (i.e., drinking at least twice the binge threshold). Results: SAM users had more past year blackouts than non-SAM users, but this effect was only significant among SAM users who had engaged in HID in the past year (nonbinge: F (5,37) = 0.50, p  = 0.49; binge: F (5,138) = 0.23, p  = 0.63; HID: F (5,328) = 4.52, p  = 0.03). Conclusions: Effects of SAM user status on the experience of alcohol-related blackouts may be limited to individuals who engage in HID.

Background: Prescription opioid misuse (POM) is often implicated in heroin initiation, despite evidence that POM does not predict heroin initiation any better than other drug use. Additionally, prescription misuse and illicit use behaviors tend to respectively "cluster" together. This study aimed to test a series of theory-driven factor models to explore how POM and heroin use are situated within the broader constellation of drug use that typically occurs alongside opioid (mis)use., Methods: 36,309 individuals from NESARC-III (56.31% female; mean age=45.63 [SD=17.53]) reported their lifetime (mis)use of prescription opioids, prescription stimulants, prescription sedatives, heroin, cannabis, cocaine/crack, illicit stimulants (e.g., methamphetamine), club drugs, hallucinogens, and inhalants, and were administered a DSM-5 substance use disorder (SUD) assessment. Bifactor, correlated factors, and one-factor confirmatory factor models were fit using all drug use/SUD variables and subsequently compared., Results: POM was most strongly correlated with prescription sedative misuse; heroin use was most strongly correlated with cocaine/crack use. All factor models fit the data well. Highly correlated factors and patterns of factor loadings suggested that POM and heroin use were most parsimoniously captured within a general factor alongside all other forms of drug use. This was also the case for SUD. Additional analyses testing an alternate factor structure provided further support for unidimensionality., Conclusions: POM and heroin use, as well as prescription- and heroin-based SUDs, were neither separable nor distinctly associated. Future research should account for other drug use more comprehensively rather than isolating POM as a primary risk factor in heroin use and use disorder., Competing Interests: Declaration of Competing Interest No conflict declared.

Background: Drug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue., Methods: A total of 2410 individual Australian twins [M age = 31.77 (s.d. = 2.48); 67% women] were interviewed about prescription misuse and illicit use of opioids and stimulants. Univariate and bivariate biometric models partitioned variances and covariances into additive genetic, shared environmental, and unique environmental influences across drug types., Results: Variation in the propensity to misuse prescription opioids was attributable to genes (41%) and unique environment (59%). Illicit opioid use was attributable to shared (71%) and unique (29%) environment. Prescription stimulant misuse was attributable to genes (79%) and unique environment (21%). Illicit stimulant use was attributable to genes (48%), shared environment (29%), and unique environment (23%). There was evidence for genetic influence common to both stimulant types, but limited evidence for genetic influence common to both opioid types. Bivariate correlations suggested that prescription opioid use may be more genetically similar to prescription stimulant use than to illicit opioid use., Conclusions: Prescription opioid misuse may share little genetic influence with illicit opioid use. Future research may consider avoiding unitary drug classifications, particularly when examining genetic influences.

Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene-environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age 2 , cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene-environment correlation with adolescent alcohol use at all PGS thresholds ( p s <.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (Δ R 2 ranged from 0.5% to 1.1%). The positive gene-environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors.

Main Objective: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic., Study Design and Methods: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission., Results and Significance: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months., Conclusions: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528)., Competing Interests: The authors have declared that no competing interests exist.

Gambling disorder is associated with suicidal behaviors, but it is not clear whether the association is due to common etiologic factors or to gambling disorder being causally related to suicidality. This question was examined from epidemiologic, longitudinal, and discordant twin study perspectives. The results suggested that the causes of the association with disordered gambling differed for suicidal ideation, plan, and attempt, and differed for men and women. The association of suicidal thoughts with disordered gambling was non-causally explained by common genetic influences among women (but not men). Conversely, there was evidence consistent with a potentially causal influence of disordered gambling on suicide attempt among men (but not women), which might have been related to gambling-related financial problems. The use of monetary data to identify individuals experiencing financial harms associated with their gambling may represent a more practicable target for screening, intervention, and prevention and may reduce gambling-related financial crises, thereby warding off a potential gambling-related suicide attempt., Competing Interests: Declarations of Interest: None.

Background: Despite abundant research on the potential causal influence of childhood maltreatment (CM) on psychological maladaptation in adulthood, almost none has implemented the discordant twin design as a means of examining the role of such experiences in later disordered gambling (DG) while accounting for genetic and family environmental confounds. The present study implemented such an approach to disentangle the potential causal and familial factors that may account for the association between CM and DG., Methods: Participants were 3750 twins from the Australian Twin Registry [Mage = 37.60 (s.d. = 2.31); 58% female]. CM and DG were assessed separately via two semi-structured telephone interviews. Random-intercept generalized linear mixed models were fit to the data; zygosity, sex, educational attainment, childhood psychiatric disorder, adult antisocial behavior, and alcohol use disorder (AUD) were included as covariates., Results: Neither quasi-causal nor familial effects of CM predicted DG after adjusting for covariates. Educational attainment appeared to reduce the risk of DG while AUD appeared to increase risk; evidence also emerged for familial effects of antisocial behavior on DG. Post-hoc analyses revealed a familial effect of CM on antisocial behavior, indicating that the association between CM and DG identified in unadjusted models and in prior studies may be accounted for by genetic and shared family environmental effects of antisociality., Conclusions: These findings add to the meager literature showing that CM does not exert a causal effect on DG, and present novel evidence that familial effects of antisocial behavior may account for the association between CM and DG identified in extant non-twin research.

Background and Aims: Previous research has demonstrated phenotypical associations between disordered gambling (DG) and Big 5 personality traits, and a twin study suggested that shared genetic influences accounted for a substantial portion of this relation. The present study examined associations between DG and polygenic scores (PSs) for Big 5 traits to measure the shared genetic underpinnings of Big 5 personality traits and DG., Design: Zero-inflated negative binomial regression models estimated associations between Big 5 PSs and past-year and life-time assessments of DG in a longitudinally assessed population-based birth cohort., Setting: United Kingdom., Participants: A total of 4729 unrelated children of European ancestry from the Avon Longitudinal Study of Parents and Children (ALSPAC) with both phenotypical and genetic data., Measurements: Phenotypical outcomes included past-year assessment of DG using the problem gambling severity index (PGSI) and life-time assessment of DSM-IV pathological gambling symptoms (DPG) across the ages of 17, 20 and 24 years. Polygenic scores were derived for the Big 5 personality traits of agreeableness, extraversion, conscientiousness, openness and neuroticism using summary statistics from genome-wide association studies (GWAS)., Findings: PSs for agreeableness [β= - 0.25, standard error (SE) = 0.054, P = 3.031e-6, ΔR 2  = 0.008] and neuroticism (β=0.14, SE = 0.046, P = 0.0017, ΔR 2  = 0.002) significantly predicted PGSI scores over and above included covariates (i.e. sex and first five ancestral principal components). PSs for agreeableness (β= - 0.20, SE = 0.056, P = 0.00036, ΔR 2  = 0.003) and neuroticism, when interactions with age were taken into account (β = 0.29, SE = 0.090, P = 0.002, ΔR 2  = 0.004), also predicted DPG scores., Conclusions: Polygenic contributions to low agreeableness and high neuroticism appear to predict two measures of disordered gambling (problem gambling severity index and life-time assessment of DSM-IV pathological gambling symptoms). Polygenic scores for neuroticism interact with age to suggest that the positive association becomes stronger from adolescence through young adulthood., (© 2021 Society for the Study of Addiction.)

Background: The role of alcohol sensitivity in the experience of blacking out and passing out has not been well established. Here, we examined the relation between individual differences in alcohol sensitivity (i.e., numbers of drinks required to experience various effects of alcohol) and reports of blacking out and passing out in the past year., Methods: Participants (925 healthy, underage college student drinkers) completed the Alcohol Sensitivity Questionnaire (ASQ) and reported on their past year blacking out and passing out experiences., Results: The fit of the ASQ's 2-factor structure was fair (CFI = 0.90, RMSEA = 0.09) in this sample of underage drinkers. In unadjusted models, higher ASQ scores (i.e., requiring more drinks to experience effects, indicating lower alcohol sensitivity) were associated with experiencing more blackouts (IRR = 1.68 [1.31-2.15]) and passing out (IRR = 2.25 [1.59-3.18]) in the past year. After controlling for typical consumption, however, higher ASQ scores were associated with fewer past-year blackouts (IRR = 0.76 [0.60-0.98]). Total ASQ scores moderated the relationship between typical alcohol consumption and blackout occurrence (interaction IRR = 0.96 [0.93-0.98]), but not passing out occurrence (interaction IRR = 0.95 [0.89-1.01]), with the quantity of alcohol consumed more strongly associated with blackout occurrence among higher-sensitivity than lower-sensitivity drinkers., Conclusions: These findings are consistent with prior work suggesting that low sensitivity may act as a paradoxical risk factor for certain heavy drinking effects, contributing to higher levels of alcohol consumption and more frequent negative consequences while also conferring protection (relative to high-sensitivity peers) at a given level of alcohol exposure., (© 2021 by the Research Society on Alcoholism.)

Aims: To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued ("desistant") and persistent drug use on drug use correlates., Design: Latent class analysis was applied to data from a cross-sectional self-report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes., Setting: Computer-assisted telephone interview in respondents' homes., Participants: A total of 3785 individual twins and siblings (1365 men, 2420 women; M age  = 32) from the Australian Twin Registry Cohort III., Measurements: A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality., Findings: A five-class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30-0.35) than dizygotic pairs (same-sex k = 0.19-0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a 2  = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14-28.01), younger first substance use (OR = 0.82-0.83), more drug use opportunity (OR = 10.66-66.06), and more drug-using peers (OR = 4.66-9.20)., Conclusions: Unique patterns of declined/discontinued ("desistant") and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes., (© 2020 Society for the Study of Addiction.)

Marriage and parenthood are associated with alcohol use and use disorder (AUD), although they are confounded such that many studies struggle to identify their unique and/or causal effects. The present study utilized a genetically informed discordant twin design that strengthens the putative causal role of marital and parental status in the presentation of AUD symptoms by using each individual's cotwin as their own control while simultaneously modeling both predictors among men and women. Participants were 980 complete same-sex twin pairs from the Australian Twin Registry ( M age = 31.70 [ SD = 2.48]; 71% women). Marital status, parental status, and past year AUD symptoms were assessed via semistructured interview. Three random-intercept generalized linear mixed models were fit in men and women including (a) marital status only, (b) parental status only, and (c) both marital and parental status; demographics, past year pregnancy, age of first drink, age of regular drinking, personality traits, and antisociality were included as covariates. Models tested for quasi-causal and familial effects. The sole-predictor marital status model (Model 1) provided the best fit among men, while the simultaneous-predictor marital and parental status model (Model 3) provided the best fit among women. Sole-predictor models showed familial effects of both predictors among men and quasi-causal and familial effects of both predictors among women; the simultaneous-predictor model revealed familial effects of marital status only among men and quasi-causal effects of parental status only among women. The present study elucidates important sex differences in the presentation of AUD among midlife adults in the context of notable developmental milestones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Age of first drink (AFD) has repeatedly been found to be associated with alcohol use disorder (AUD); however, some studies suggest this is a noncausal effect that may be due to childhood risk factors or familial influences. In contrast to indicators of any early alcohol use, such as AFD, indicators of a pattern of repeated drinking may be more likely to be causally associated with later problematic alcohol use. The current study examined AFD and age of onset of regular drinking (ARD; defined as drinking at least once a month for 6 or more months) as quasicausal predictors of lifetime AUD symptoms. Participants were 3,005 adult Australian twins who reported having been regular drinkers in their lifetime. Semistructured interviews were conducted to assess AFD, ARD, AUD, externalizing symptomatology, and other substance use. Personality traits were assessed via questionnaire. Unadjusted and adjusted multilevel discordant twin models were conducted using data from 1,041 complete twin pairs; adjusted models included socioeconomic status, personality, conduct disorder, and early initiation of regular smoking and marijuana use as covariates. Results from fully adjusted models controlling for familial confounds provided evidence for a causal influence of ARD on AUD symptoms, whereby twins with an earlier age of regular drinking than their cotwin had more lifetime AUD symptoms. However, AFD did not significantly predict AUD symptoms after adjusting for confounds. These results suggest that early regular drinking may serve as a causal risk factor for future problems, while early initiation of any alcohol use may indicate genetic liability. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Professor Nicholas G. Martin, from QIMR Berghofer Medical Research Institute in Brisbane, Australia, is a world leader in the effort to understand the genetic architecture underlying disordered gambling. This article pays tribute to Nick and his almost two decades of gambling research, highlighting his many strengths, ranging from the use of ingenious recruitment approaches, twin study methods, genomewide association studies, to facilitating international collaborations.

Background: Many adult drinkers consume far beyond the binge threshold. This "high-intensity drinking" (HID), defined as 2 (HID-2) and 3 (HID-3) times the binge threshold, is of public health interest due to its role in acute alcohol-related harms. Research on HID has mostly been limited to college-aged young adults, focused on contextual factors, and neglected the potential role of genetic influences on the propensity to engage in HID., Methods: Structured diagnostic interviews assessing past-year alcohol involvement were conducted with 3,785 individuals (1,365 men, 2,420 women; M age  = 32, range = 21 to 46), including 3,314 twins and 471 nontwin siblings from the Australian Twin Registry. Multinomial logistic regression analyses were conducted to compare HID-2 and HID-3 to binge drinking on demographic correlates, drinking characteristics, and drinking-related consequences. Biometric modeling was conducted to estimate the role of genetic, common, and individual-specific environmental factors in HID propensity., Results: Among past-year drinkers, the prevalence of HID-2 and HID-3 was both 22%, with men disproportionally represented. The frequencies of drinking, intoxication, and binge drinking significantly increased across the heavier drinking categories, which also evidenced higher average consumption quantities and higher rates of alcohol-related consequences. The propensity to engage in HID was significantly heritable (A = 37% [95% CI: 28 to 46%]), with individual-specific environmental influences accounting for the remainder of the variance., Conclusions: This study convincingly demonstrates that HID is not restricted to college-aged young adults, but also can be highly prevalent among those of working age, and that the propensity to engage in HID is partially explained by genetic influences., (© 2020 by the Research Society on Alcoholism.)

Background: Cannabis use patterns vary considerably, with many users reporting simultaneous and non-simultaneous use (co-use) of other substances. Despite this, little research has examined the extent to which subtypes of cannabis users may be identified based on their simultaneous and co-use behaviors., Methods: The sample consisted of adult Australian twins and siblings who reported lifetime cannabis use (n = 2590). A latent class analysis was conducted to determine subtypes of cannabis users based on five indicators of substance co-use and simultaneous use. Adolescent correlates (age of substance initiation and conduct disorder) and adult correlates (substance use/disorder and depression) of class membership were assessed. Twin similarity for class membership was also examined., Results: Four subtypes of users were identified: 1) alcohol co-users, 2) simultaneous alcohol users, 3) simultaneous tobacco users, and 4) simultaneous alcohol, tobacco, and drug users. Compared to co-users of alcohol, simultaneous alcohol users were at increased risk for alcohol problems. Patterns of use that involved simultaneous tobacco and cannabis use (i.e., simultaneous tobacco users and simultaneous alcohol, tobacco, and drug users) were associated with the most problematic outcomes, including substance use and disorder. There was evidence for genetic influences (12-58%) on cannabis use patterns, with higher concordance for latent class membership among monozygotic compared to dizygotic twins (χ 2 (1) = 7.19, p = 0.007)., Conclusions: The current study identified four classes of cannabis users at varying degrees of risk. Results suggest that simultaneous tobacco and cannabis use may be especially associated with deleterious outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Disordered gambling (DG) is a rare but serious condition that results in considerable financial and interpersonal harms. Twin studies indicate that DG is heritable but are silent with respect to specific genes or pathways involved. Existing genomewide association studies (GWAS) of DG have been substantially underpowered. Larger GWAS of other psychiatric disorders now permit calculation of polygenic risk scores (PRSs) that reflect the aggregated effects of common genetic variants contributing risk for the target condition. The current study investigated whether gambling and DG are associated with PRSs for four psychiatric conditions found to be comorbid with DG in epidemiologic surveys: major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). Genotype data and survey responses were analyzed from the Wave IV assessment (conducted in 2008) of the National Longitudinal Study of Adolescent to Adult Health, a representative sample of adolescents recruited in 1994-1995 and followed into adulthood. Among participants classified as having European ancestry based on genetic analysis (N = 5215), 78.4% reported ever having gambled, and 1.3% reported lifetime DG. Polygenic risk for BD was associated with decreased odds of lifetime gambling, OR = 0.93 [0.87, 0.99], p = .045, pseudo-R2(%) = .12. The SCZ PRS was associated with increased odds of DG, OR = 1.54 [1.07, 2.21], p = .02, pseudo-R2(%) = .85. Polygenic risk scores for MDD and ADHD were not related to either gambling outcome. Investigating features common to both SCZ and DG might generate valuable clues about the genetically influenced liabilities to DG.

Background: Gambling disorder (GD), recognized in Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) as a behavioral addiction, is associated with a range of adverse outcomes. However, there has been little research on the genetic and environmental influences on the development of this disorder. This study reports results from the largest twin study of GD conducted to date., Methods: Replication and combined analyses were based on samples of 3292 (mean age 31.8, born 1972-79) and 4764 (mean age 37.7, born 1964-71) male, female, and unlike-sex twin pairs from the Australian Twin Registry. Univariate biometric twin models estimated the proportion of variation in the latent GD liability that could be attributed to genetic, shared environmental, and unique environmental factors, and whether these differed quantitatively or qualitatively for men and women., Results: In the replication study, when using a lower GD threshold, there was evidence for significant genetic (60%; 95% confidence interval (CI) 45-76%) and unique environmental (40%; 95% CI 24-56%), but not shared environmental contributions (0%; 95% CI 0-0%) to GD liability; this did not significantly differ from the original study. In the combined analysis, higher GD thresholds (such as one consistent with DSM-5 GD) and a multiple threshold definitions of GD yielded similar results. There was no evidence for quantitative or qualitative sex differences in the liability for GD., Conclusions: Twin studies of GD are few in number but they tell a remarkably similar story: substantial genetic and unique environmental influences, with no evidence for shared environmental contributions or sex differences in GD liability.

Background: Individuals differ in their sensitivity to alcohol's physiological effects, including blacking and passing out. Blackouts are periods of impaired memory formation when an individual engages in activities they later cannot recall, while passing out results in loss of consciousness., Methods: The sample consisted of 3,292 adult twins from the Australian Twin Registry. Univariate twin analyses were conducted to examine the contributions of genetic and environmental influences to blacking and passing out occurrence and susceptibility (accounting for frequency of intoxication). Evidence for shared etiology of susceptibility to blacking and passing out was examined using bivariate twin analyses., Results: Although blacking and passing out were strongly associated (odds ratio (OR) = 4.45, 95% confidence interval (CI): [3.85, 5.14]), the genetic epidemiology was quite different. Genetic (43%) and nonshared environmental (57%) influences contributed to liability for blackout occurrence. For passing out occurrence, there was evidence of sex differences. Among men, genetic (32%) and nonshared environmental (68%) influences contributed, whereas among women, there were shared (29%) and nonshared environmental (72%) influences. After accounting for frequency of intoxication, genetic influences on blackout susceptibility remained significant; in contrast, only nonshared environmental influences were significant for passing out susceptibility. There was evidence for overlapping genetic and nonshared environmental factors influencing susceptibility to blacking and passing out among men; among women, there were overlapping nonshared environmental influences., Conclusions: Blacking and passing out are 2 common sedative-like effects of heavy drinking, and people differ considerably in their susceptibility to these effects. This study suggests that differences in blackout susceptibility can be explained by genetic factors in both men and women, while differences in susceptibility to pass out after consuming alcohol may be attributable to environmental influences, particularly among women. These environmental factors may include changing social and cultural norms about alcohol use, drinking context, and the type(s) of alcohol consumed., (© 2019 by the Research Society on Alcoholism.)

The Diagnostic and Statistical Manual of Mental Disorders (DSM ; 5th ed.) reassignment of gambling disorder as an addictive disorder alongside the substance-related addictive disorders encourages research into their shared etiologies. The aims of this study were to examine: (a) the associations of Big Five personality dimensions with alcohol, nicotine, cannabis, and gambling disorders, (b) the comorbidity between these disorders, (c) the extent to which common personality underpinnings explain comorbidity, (d) whether results differed for men and women, and (e) the magnitude of personality differences corresponding to the 4 disorders. Participants were 3,785 twins and siblings (1,365 men, 2,420 women; M age = 32 years, range = 21-46 years) from the Australian Twin Registry who completed psychiatric interviews and Big Five personality inventories. The personality profile of high neuroticism, low agreeableness, and low conscientiousness was associated with all 4 addictive disorders. All but 1 of the pairwise associations between the disorders were significant. After accounting for Big Five traits, the associations were attenuated to varying degrees but remained significant. The results were generally similar for men and women. The results suggest that the Big Five traits of neuroticism, agreeableness, and conscientiousness are associated with the general propensity to develop an addictive disorder and may in part explain their co-occurrence; however, they may be more broadly associated with the propensity for any psychiatric disorder. The effect sizes of the personality associations suggest that the diagnosis of gambling disorder as operationalized by the DSM may be more severe than the other addictive disorders. Calibration of the diagnosis of gambling disorder to the other addictive disorders may be warranted. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background and Aims: Geographic differences in rates of alcohol use disorder suggest that environmental factors and gene-environment interactions are likely to play an important role in its genesis. We aimed to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to develop alcohol problems., Design: Cross-sectional twin/sibling study., Setting: United States., Participants: The participants were 18-26-year-old twin, full- and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health., Measurements: Participants completed in-home interviews in which past year alcohol problems were assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level., Findings: There was evidence that estimates of genetic and environmental influences on alcohol problems varied as a function of the density of alcohol outlets in the community. The heritability of alcohol problems for those residing in a neighborhood with more than 10 on-premises outlets was 78% (95% confidence limits = 52-100%), compared with 11% (95% confidence limits = 0-29%) for those in a neighborhood with no on-premises outlets. This moderating effect of alcohol outlet density was not explained by state of residence, population density or neighborhood socio-demographic characteristics., Conclusions: Individuals who are genetically predisposed to develop alcohol problems may be especially sensitive to the influence of many alcohol outlets in their community., (© 2018 Society for the Study of Addiction.)

The quality of the neighborhood in which one lives has been linked to disordered gambling (DG), but whether this reflects a causal relation has not yet been empirically examined. Participants were 3,450 Australian twins who completed assessments of past-year DG and personality and for whom census-derived indicators of disadvantage were used to characterize their neighborhood. Multilevel models were employed to estimate within-twin-pair and betweentwin-pair effects of neighborhood disadvantage on DG, with the within-twin-pair effect representing a potentially causal association and the between-twin-pair effect representing a noncausal association. There was robust evidence for a potentially causal (as well as a non-causal) effect of neighborhood disadvantage on DG (in contrast, parallel analyses of past-year alcohol use disorder failed to find evidence of a potentially causal effect). These results support efforts focused on identifying the active ingredients contributing to the effect of neighborhood disadvantage on DG and developing interventions to limit their impact.

Background: Genetic influences on alcohol involvement are likely to vary as a function of the 'alcohol environment,' given that exposure to alcohol is a necessary precondition for genetic risk to be expressed. However, few gene-environment interaction studies of alcohol involvement have focused on characteristics of the community-level alcohol environment. The goal of this study was to examine whether living in a community with more alcohol outlets would facilitate the expression of the genetic propensity to drink in a genetically-informed national survey of United States young adults., Methods: The participants were 2434 18-26-year-old twin, full-, and half-sibling pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Participants completed in-home interviews in which alcohol use was assessed. Alcohol outlet densities were extracted from state-level liquor license databases aggregated at the census tract level to derive the density of outlets., Results: There was evidence that the estimates of genetic and environmental influences on alcohol use varied as a function of the density of alcohol outlets in the community. For example, the heritability of the frequency of alcohol use for those residing in a neighborhood with ten or more outlets was 74% (95% confidence limits = 55-94%), compared with 16% (95% confidence limits = 0-34%) for those in a neighborhood with zero outlets. This moderating effect of alcohol outlet density was not explained by the state of residence, population density, or neighborhood sociodemographic characteristics., Conclusions: The results suggest that living in a neighborhood with many alcohol outlets may be especially high-risk for those individuals who are genetically predisposed to frequently drink.

Objective: Adolescence is an optimal developmental stage for examining the interplay of environmental factors and the genetic risk for alcohol involvement. The current study aimed to examine how socioeconomic status might interact with genetic risk for alcohol involvement among adolescents., Method: A total of 839 same-sex adolescent twin pairs (509 monozygotic and 330 dizygotic) from the 1962 National Merit Twin Study completed a questionnaire containing items assessing alcohol involvement. Twins were approximately 17 years old at the time of participation. Parents provided reports of family income and educational attainment. Models were fit examining parental education and family income as moderators of genetic and environmental influences on alcohol use., Results: There was evidence for moderation of genetic and environmental influences on alcohol involvement by family income. For twins with the lowest levels of family income, genetic and shared environmental influences accounted for 50% and 26% of the variance in alcohol involvement, respectively, compared with 2% and 67% of the variance among those at the highest level of income., Conclusions: These findings suggest that etiological influences on alcohol involvement vary as a function of an adolescent's socioeconomic status., Competing Interests: Christal N. Davis and Wendy S. Slutske declare no conflicts of interest.

Background: Daily drinking is an important public health concern and informative for evaluating diagnostic classification. In particular, daily binge drinkers might be considered as the prototype of some forms of alcoholism, as this drinking pattern may drive many alcohol use disorder (AUD) symptoms. However, daily drinking potentially captures a wide range of drinkers, including light-moderate daily drinkers who exhibit presumed control over their drinking behavior and might benefit from salutary effects on health. This study examined the heterogeneity of daily drinkers in detail., Methods: Data from the 2 waves of the National Epidemiologic Survey on Alcohol and Related Conditions were used. Participants who reported drinking "every day" during the last 12 months were classified as daily drinkers. A series of regression and logistic regression analyses were conducted to investigate the association between daily drinking and various outcomes., Results: Daily drinkers were found to vary considerably from each other with respect to diagnostic status, level of consumption, demographic composition, and a range of drinking and health correlates. Further, a substantial number of daily binge drinkers were not diagnosed with AUD under the DSM-IV or DSM-5, although in most groups, the DSM-5 criteria diagnosed a larger percentage of participants., Conclusions: Daily drinkers represent a highly heterogeneous group, and the correlates of daily drinking depend on the usual quantity of daily drinks and the frequency of alcohol-related problems in a given sample. Moreover, AUD, defined both according to DSM-IV and DSM-5, did not capture more than 68% of daily binge drinkers. Given that daily binge drinking is an extremely high threshold for use, this finding may present a challenge for our current classification system., (Copyright © 2018 by the Research Society on Alcoholism.)

Objective: Dual-systems models hypothesize that individuals who tend to be drawn to risky behavior and are low in self-control are at greatest risk for alcohol use disorder (AUD). Importantly, these models assume that behavioral approach tendencies and self-control are distinct. This study investigated hypotheses and assumptions central to dual-systems models., Method: Participants were 3,509 members of a national twin registry (58% female). Structured interviews assessed alcohol use and AUD symptoms. Self-report questionnaires assessed individual differences in approach tendencies, namely for general risky behavior (sensation seeking) and substance use (positive expectancies), and behavioral control. Regression models tested nonadditive, interaction effects on alcohol involvement, as proposed by the dual-systems model. Multivariate behavior genetic models investigated the incremental validity of these interaction effects and whether approach tendencies and behavioral control explain distinct variance in alcohol involvement., Results: In regression models, we found interaction effects consistent with the dual-systems model for women but in the opposite direction for men. After accounting for additive main effects in behavior genetic models, however, these interaction effects played a negligible role phenotypically and genetically. Further, sensation seeking and positive expectancies explained phenotypic and genetic variance in alcohol involvement that was distinct from behavioral control. Behavioral control, however, did not explain distinct variance in alcohol involvement., Conclusions: Contrary to dual-systems models, this study suggests that all of the variance in alcohol involvement explained by behavioral control is also shared with the tendency to engage in risky behavior (sensation seeking) and substance use (positive expectancies). Further, interaction effects central to dual-systems models failed to explain additional variance beyond basic main effects. Thus, more parsimonious models may better explain AUD.

Social changes, such as the expansion of legal forms of gambling, can influence not only the prevalence of gambling, but can also shape the relative importance of genetic and environmental contributions to individual differences in the propensity to gamble. In the present study, I examined differences in the prevalence and in the relative contribution of genetic and environmental factors to gambling involvement in the United States in 1962 versus 2002. The data came from two sources: (1) a survey of 839 17-year-old same-sex twin pairs from the National Merit Scholarship Qualifying Test twin study, and (2) an interview of 477 18- to 26-year-old same-sex twin pairs from Wave III of the National Longitudinal Study of Adolescent to Adult Health. Similar measures of gambling participation were included in the two studies. Evidence for a genotype-by-time interaction was evaluated by testing whether the contribution of genetic influences was greater in the more recently born cohort of twins. Despite the major changes in the gambling landscape over the intervening 40 years, there was no evidence for such an interaction. The contribution of genetic factors and environmental factors did not significantly differ and there was no evidence for genetic influences at either time point. Instead, the variation in the propensity to gamble was explained nearly equally by common and unique environmental factors. Explanations for this surprising finding are discussed.

Background: Distinct changes in alcohol use etiologies occur during adolescence and young adulthood. Additionally, measured environments known to influence alcohol use such as peers and parenting practice can interact or be associated with this genetic influence. However, change in genetic and environmental influences over age, as well as how associations with measured environments change over age, is understudied., Methods: The National Longitudinal Study of Adolescent Health (Add Health) sibling subsample was used to examine data-driven biometric models of alcohol use over ages 13 to 27. Associations between friends' drinking, parental autonomy granting, and maternal closeness were also examined., Results: The best-fitting model included a 5-factor model consisting of early (ages 13 to 20) and overall (ages 13 to 27) additive genetic and unique environmental factors, as well as 1 overall common environment factor. The overall additive genetic factor and the early unique environment factor explained the preponderance of mean differences in the alcohol use over this portion of the life span. The most important factors explaining variance attributed to alcohol use changed over age. Additionally, friend use had the strongest associations with genetic and environmental factors at all ages, while parenting practices had almost no associations at any age., Conclusions: These results supplement previous studies indicating changes in genetic and environmental influences in alcohol use over adolescence and adulthood. However, prior research suggesting that constraining exogenous predictors of genetic and environmental factors to have effects of the same magnitude across age overlooks the differential role of factors associated with alcohol use during adolescence. Consonant with previous research, friend use appears to have a more pervasive influence on alcohol use than parental influence during this age. Interventions and prevention programs geared toward reducing alcohol use in younger populations may benefit from focus on peer influence., (Copyright © 2017 by the Research Society on Alcoholism.)

Adolescents in rural and urban areas may experience different levels of environmental restrictions on alcohol use, with those in rural areas experiencing greater monitoring and less access to alcohol. Such restrictions may limit expression of genetic vulnerability for alcohol use, resulting in a gene-environment interaction (G × E). This phenomenon has previously been reported in Finnish and Minnesota adolescents. The current study used data from 839 same-sex twin pairs from the 1962 National Merit Scholarship Qualifying Test to determine whether the G × E interaction would be evident in this earlier time period. We also assessed whether the G × E interaction would be moderated by sex, and whether family socioeconomic status (SES; income and parental education) may mediate the G × E interaction. Findings showed the expected interaction among females, with a weaker contribution of genes (2 vs. 44%) and greater contribution of shared environment (62 vs. 29%) to variation in alcohol involvement among rural as compared to urban residents. The G × E interaction was not observed among males, and operated independently from differences in family SES among rural and urban adolescents. This study represents a partial replication in a novel setting of the moderation of the genetic contribution to alcohol use by rural/urban residency, and suggests that SES differences may not explain this effect.

Objective: The findings of previous research that examined relationships between popularity and alcohol use in adolescents have been mixed, and few hypotheses have proposed mechanisms for this relationship. The current study expands on previous literature (a) by examining a possible mechanism that can explain the relation between popularity and alcohol use (home access to alcohol) and (b) by using another sociometric measure ("betweenness"), beyond popularity, that may relate more to home alcohol access., Method: Using network-level data from adolescents in 9th-11th grades in eight schools within two in-home waves of the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined two sociometric measures of social status: popularity (number of schoolmates who nominated participants as a friend) and betweenness (level of ties participants have to multiple social subgroups within a network)., Results: Betweenness, but not popularity, related to later alcohol use. Having home access to alcohol positively related to later alcohol use, and having friends with home access to alcohol negatively related to later alcohol use. Alcohol access was also related to later sociometric status. Friends' alcohol access negatively related to later betweenness, and personal alcohol access moderated other pathways predicting betweenness., Conclusions: Betweenness appears to play a unique role in the association between social status and alcohol use in adolescent social networks. This is potentially tied to specific ways in which adolescents may be able to access alcohol (through home or through friends with access at home). More research is necessary to examine the ways in which multiple sociometric statuses relate to the contexts in which adolescents access and use alcohol.

An individual's age at first substance use may be associated with their risk for progression toward heavier substance involvement. To our knowledge, however, no studies within nationally representative samples have examined the relation between the timing of initiation and progression in use of multiple substances. The present study employed a sample of 9,421 participants from the National Longitudinal Study of Adolescent to Adult Health who reported on their ages of tobacco, alcohol, and cannabis initiation; frequency of tobacco, alcohol, and cannabis use; and quantity of tobacco and alcohol use across 4 waves. We fit latent growth models to examine (a) associations between the age of initiation and initial status and rate of change in substance involvement, and (b) the degree to which the timing of first substance use accounted for differences in trajectories. There were significant relations between all ages of initiation and rates of change in tobacco (βs = -0.21 to -0.31, ps < .01) and alcohol use frequency (βs = 0.14 to 0.31, ps < .001), age of cannabis initiation and rate of change in tobacco use quantity (β = 0.23, p < .01), and age of tobacco initiation and rate of change in cannabis use frequency (β = -0.14, p < .01). After adjusting for age of initiation, significant associations were observed between trajectories for tobacco and alcohol (r = .43, p < .0001) and alcohol and cannabis (r = .20, p < .05). Results highlight differences in within- and cross-substance relations between the age of initiation and rate of change in use across substances. They suggest that differences in substance use trajectories are partly accounted for by age at first use. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

The current study examined a stage-based alcohol use trajectory model to test for potential causal effects of earlier drinking milestones on later drinking milestones in a combined sample of two cohorts of Australian monozygotic and same-sex dizygotic twins (N = 7,398, age M = 30.46, SD = 2.61, 61% male, 56% monozygotic twins). Ages of drinking, drunkenness, regular drinking, tolerance, first nontolerance alcohol use disorder symptom, and alcohol use disorder symptom onsets were assessed retrospectively. Ages of milestone attainment (i.e., age-of-onset) and time between milestones (i.e., time-to-event) were examined via frailty models within a multilevel discordant twin design. For age-of-onset models, earlier ages of onset of antecedent drinking milestones increased hazards for earlier ages of onset for more proximal subsequent drinking milestones. For the time-to-event models, however, earlier ages of onset for the "starting" milestone decreased risk for a shorter time period between the starting and the "ending" milestone. Earlier age of onset of intermediate milestones between starting and ending drinking milestones had the opposite effect, increasing risk for a shorter time period between the starting and ending milestones. These results are consistent with a causal effect of an earlier age of drinking milestone onset on temporally proximal subsequent drinking milestones.

Introduction: Tobacco use is associated with variation at the 15q25 gene cluster and the cytochrome P450 (CYP) genes CYP2A6 and CYP2B6. Despite the variety of outcomes associated with these genes, few studies have adopted a data-driven approach to defining tobacco use phenotypes for genetic association analyses. We used factor analysis to generate a tobacco use measure, explored its incremental validity over a simple indicator of tobacco involvement: cigarettes per day (CPD), and tested both phenotypes in a genetic association study., Methods: Data were from the University of California, San Francisco Family Alcoholism Study (n = 1942) and a Native American sample (n = 255). Factor analyses employed a broad array of tobacco use variables to establish the candidate phenotype. Subsequently, we conducted tests for association with variants in the nicotinic acetylcholine receptor and CYP genes. We explored associations with CPD and our measure. We then examined whether the variants most strongly associated with our measure remained associated after controlling for CPD., Results: Analyses identified one factor that captured tobacco-related problems. Variants at 15q25 were significantly associated with CPD after multiple testing correction (rs938682: p = .00002, rs1051730: p = .0003, rs16969968: p = .0003). No significant associations were obtained with the tobacco use phenotype; however, suggestive associations were observed for variants in CYP2B6 near CYP2A6 (rs45482602: ps = .0082, .0075) and CYP4Z2P (rs10749865: ps = .0098, .0079)., Conclusions: CPD captures variation at 15q25. Although strong conclusions cannot be drawn, these finding suggest measuring additional dimensions of problems may detect genetic variation not accounted for by smoking quantity. Replication in independent samples will help further refine phenotype definition efforts., Implications: Different facets of tobacco-related problems may index unique genetic risk. CPD, a simple measure of tobacco consumption, is associated with variants at the 15q25 gene cluster. Additional dimensions of tobacco problems may help to capture variation at 19q13. Results demonstrate the utility of adopting a data-driven approach to defining phenotypes for genetic association studies of tobacco involvement and provide results that can inform replication efforts., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Mental health disorders commonly co-occur, even between conceptually distinct syndromes, such as internalizing and externalizing disorders. The current study investigated whether phenotypic, genetic, and environmental variance in negative emotionality and behavioral control account for the covariation between major depressive disorder (MDD) and alcohol use disorder (AUD)., Method: A total of 3623 members of a national twin registry were administered structured diagnostic telephone interviews that included assessments of lifetime histories of MDD and AUD, and were mailed self-report personality questionnaires that assessed stress reactivity (SR) and behavioral control (CON). A series of biometric models were fitted to partition the proportion of covariance between MDD and AUD into SR and CON., Results: A statistically significant proportion of the correlation between MDD and AUD was due to variance specific to SR (men = 0.31, women = 0.27) and CON (men = 0.20, women = 0.19). Further, genetic factors explained a large proportion of this correlation (0.63), with unique environmental factors explaining the rest. SR explained a significant proportion of the genetic (0.33) and environmental (0.23) overlap between MDD and AUD. In contrast, variance specific to CON accounted for genetic overlap (0.32), but not environmental overlap (0.004). In total, SR and CON accounted for approximately 70% of the genetic and 20% of the environmental covariation between MDD and AUD., Conclusions: This is the first study to demonstrate that negative emotionality and behavioral control confer risk for the co-occurrence of MDD and AUD via genetic factors. These findings are consistent with the aims of NIMH's RDoC proposal to elucidate how transdiagnostic risk factors drive psychopathology.

Behavioral genetic studies have provided insights into why early substance use initiation is associated with increased risk for disorder. Few genetically informative studies, however, have operationalized initiation as the timing of first use and simultaneously modeled the timing of initiation and problematic use of multiple substances. Such research can help capture the risk associated with early initiation and determine the extent to which genetic and environmental risk generalizes across substances. This study utilized a behavior genetic approach to examine the relation between the age of substance use initiation and symptoms of substance use disorder. Participants were 7,285 monozygotic and dizygotic twins (40% male, mean age at interview = 30.6 years) from the Australian Twin Registry who reported on their ages of tobacco, alcohol, and cannabis initiation and symptoms of Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV) nicotine dependence, alcohol use disorder, and cannabis use disorder. Biometric modeling was conducted to (a) determine the structure of genetic and environmental influences on initiation and disorder and (b) examine their genetic and environmental overlap. The latent structure of initiation differed across men and women. The familial covariance between initiation and disorder was genetic among men and genetic and environmental among women, suggesting that the relation between first substance use and disorder is partly explained by a shared liability. After accounting for familial overlap, significant unique environmental correlations were observed, indicating that the age of initiation of multiple drugs may directly increase risk for substance-related problems. Results support the utility of conceptualizing initiation in terms of age and of adopting a multivariate approach. (PsycINFO Database Record, Competing Interests: There are no conflicts of interest to declare., ((c) 2016 APA, all rights reserved).)