Strong and weak cross-inheritance of substance use disorders in a nationally representative sample.

Substance use disorders (SUDs) are moderately to highly heritable and are in part cross-transmitted genetically, as observed in twin and family studies. We performed exome-focused genotyping to examine the cross-transmission of four SUDs: alcohol use disorder (AUD, n = 4487); nicotine use disorder (NUD, n = 4394); cannabis use disorder (CUD, n = 954); and nonmedical prescription opioid use disorder (NMPOUD, n = 346) within a large nationally representative sample (n = 36,309), the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III). All diagnoses were based on in-person structured psychiatric interview (AUDADIS-5). SUD cases were compared alone and together to 3959 "super controls" who had neither a SUD nor a psychiatric disorder using an exome-focused array assaying 363,496 SNPs, yielding a representative view of within-disorder and cross-disorder genetic influences on SUDs. The 29 top susceptibility genes for one or more SUDs overlapped highly with genes previously implicated by GWAS of SUD. Polygenic scores (PGS) were computed within the European ancestry (EA) component of the sample (n = 12,505) using summary statistics from each of four clinically distinct SUDs compared to the 3959 "super controls" but then used for two distinctly different purposes: to predict SUD severity (mild, moderate, or severe) and to predict each of the other 3 SUDs. Our findings based on PGS highlight shared and unshared genetic contributions to the pathogenesis of SUDs, confirming the strong cross-inheritance of AUD and NUD as well as the distinctiveness of inheritance of opioid use disorder.

Prevalence, correlates, comorbidity and treatment of electronic nicotine delivery system use in the United States.

INTRODUCTION: This study presents nationally representative data on the prevalence, correlates, psychiatric comorbidity and treatment (including pharmacological and nonpharmacological) among electronic nicotine delivery system (ENDS) users. METHODS: Face-to-face interviews in the National Epidemiologic Survey on Alcohol and Related Conditions-III. RESULTS: Prevalences of 12-month and lifetime ENDS use were 3.8% (SE=0.14) and 5.4% (SE=0.17). Odds of ENDS use were greater among men than women, regardless of timeframe. Rates were lower among Blacks, Hispanics and Asians/Pacific Islanders relative to Whites. Odds of 12-month and lifetime ENDS use was also higher among younger (<65years) than older (≥65years) individuals and higher among individuals with high school education relative to these with some college education. Odds of 12-month and lifetime ENDS use was also higher among individuals with incomes <$70,000.00 compared with those with incomes≥$70,000.00 and higher among the previously married relative to those who were currently married. Associations between 12-month ENDS use and severe nicotine use disorder were strong, whereas associations with other substance use disorders and borderline and antisocial personality disorders were modest (AORs=1.3-2.6). Rates of treatment seeking to cut down or quit tobacco or nicotine use (12-month, 25.0% (SE=1.6); lifetime, 24.4% (SE=1.4)) were low. CONCLUSIONS: ENDS use is substantially comorbid, especially with nicotine use disorder. Virtually all ENDS users smoked cigarettes. Research is needed to understand their role in smoking cessation, adverse effects on bodily systems and their potential for addiction and comorbidity.

The Epidemiology of DSM-5 Nicotine Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III.

OBJECTIVE: To present nationally representative information on the prevalence, correlates, psychiatric comorbidity, and treatment of DSM-5 nicotine use disorder (NUD) and the public health burden of US cigarette consumption among adults with NUD and other psychiatric disorders. METHODS: Using data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (N = 36,309), we conducted weighted cross-tabulations and multivariate logistic regression analyses to estimate prevalences and examine comorbidity of NUD. RESULTS: Prevalences of 12-month and lifetime DSM-5 NUD were 20.0% and 27.9%, respectively. Nicotine use disorder was more frequent among men, non-Hispanic whites, younger individuals, the previously married, those with less education and lower incomes, and those residing in rural areas. Adjusting for sociodemographic characteristics and additional psychiatric comorbidity, 12-month NUD and lifetime NUD were significantly associated with other substance use and antisocial personality disorders (odds ratios [ORs] = 1.5-5.1, 12-month; 1.5-5.6, lifetime). Twelve-month severe NUD was generally associated with major depressive, bipolar I, bipolar II, panic, generalized anxiety, posttraumatic stress, and schizotypal, borderline, and antisocial personality disorders (ORs = 1.3-2.5). Individuals with current NUD and at least 1 psychiatric disorder comprised 11.1% of US adults but smoked 53.6% of total cigarettes consumed. Treatment was utilized by 20.3% of respondents with 12-month and 18.8% with lifetime NUD. CONCLUSIONS: Findings underscore the need to address nicotine use in clinical settings. Recognition of psychiatrically vulnerable subpopulations may inform etiologic research, prevention, and treatment of NUD.

Effects of State-Level Tobacco Environment on Cigarette Smoking are Stronger Among Those With Individual-Level Risk Factors.

INTRODUCTION: To better understand the impact of the state-level tobacco environment (eg, tobacco control policies, attitudes towards smoking) on cigarette smoking, we examined whether the relationship of state tobacco environments to smoking is modified by individual-level vulnerability factors. METHODS: In a nationally representative sample of US adults (N = 34 638), past-year smoking and heavy smoking were examined. State-level tobacco environment was defined by tobacco-related control policies and attitudes, ranging from permissive to restrictive; individual vulnerability was defined by childhood maltreatment and/or parental substance problems. Additive interaction tested differences in state-level tobacco environment effects on smoking and heavy smoking by individual-level vulnerability. RESULTS: Significant interactions (P values < .01) indicated that the state tobacco environment had the strongest relationship to smoking outcomes among individuals with greatest individual vulnerability. For example, among respondents with childhood maltreatment and parental substance problems, those in states with permissive tobacco environments had 13.3% greater prevalence of smoking than those in restrictive states. Among respondents with neither individual-level risk factor, those in permissive states had 2.8% greater prevalence than those in restrictive states (interaction P value = .0002). CONCLUSIONS: Further restricting states' smoking environments could help reduce the prevalence of smoking and heavy smoking, particularly among those at increased individual risk in the general population. IMPLICATIONS: This study shows that the protective effect of restrictive state-level tobacco environments on smoking or heavy smoking was stronger among those especially vulnerable due to individual-level risk factors (parental substance problems, childhood maltreatment). Thus, public health campaigns to influence attitudes towards smoking or legislation to strengthen tobacco control could have a broad effect, particularly impacting those with vulnerability to smoking, which may help decrease smoking prevalence and reduce the massive public health burden of tobacco-related morbidity and mortality.

Epidemiology of DSM-5 Drug Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions-III.

IMPORTANCE: Current information on the prevalence and sociodemographic and clinical profiles of individuals in the general population with DSM-5 drug use disorder (DUD) is limited. Given the present societal and economic context in the United States and the new diagnostic system, up-to-date national information is needed from a single uniform data source. OBJECTIVE: To present nationally representative findings on the prevalence, correlates, psychiatric comorbidity, disability, and treatment of DSM-5 DUD diagnoses overall and by severity level. DESIGN, SETTING, AND PARTICIPANTS: In-person interviews were conducted with 36,309 adults in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III, a cross-sectional representative survey of the United States. The household response rate was 72%; person-level response rate, 84%; and overall response rate, 60.1%. Data were collected April 2012 through June 2013 and analyzed from February through March 2015. MAIN OUTCOMES AND MEASURES: Twelve-month and lifetime DUD, based on amphetamine, cannabis, club drug, cocaine, hallucinogen, heroin, nonheroin opioid, sedative/tranquilizer, and/or solvent/inhalant use disorders. RESULTS: Prevalences of 12-month and lifetime DUD were 3.9% and 9.9%, respectively. Drug use disorder was generally greater among men, white and Native American individuals, younger and previously or never married adults, those with lower education and income, and those residing in the West. Significant associations were found between 12-month and lifetime DUD and other substance use disorders. Significant associations were also found between any 12-month DUD and major depressive disorder (odds ratio [OR], 1.3; 95% CI, 1.09-1.64), dysthymia (OR, 1.5; 95% CI, 1.09-2.02), bipolar I (OR, 1.5; 95% CI, 1.06-2.05), posttraumatic stress disorder (OR, 1.6; 95% CI, 1.27-2.10), and antisocial (OR, 1.4; 95% CI, 1.11-1.75), borderline (OR, 1.8; 95% CI, 1.41-2.24), and schizotypal (OR, 1.5; 95% CI, 1.18-1.87) personality disorders. Similar associations were found for any lifetime DUD with the exception that lifetime DUD was also associated with generalized anxiety disorder (OR, 1.3; 95% CI, 1.06-1.49), panic disorder (OR, 1.3; 95% CI, 1.06-1.59), and social phobia (OR, 1.3; 95% CI, 1.09-1.64). Twelve-month DUD was associated with significant disability, increasing with DUD severity. Among respondents with 12-month and lifetime DUD, only 13.5% and 24.6% received treatment, respectively. CONCLUSIONS AND RELEVANCE: DSM-5 DUD is a common, highly comorbid, and disabling disorder that largely goes untreated in the United States. These findings indicate the need for additional studies to understand the broad relationships in more detail; estimate present-day economic costs of DUDs; investigate hypotheses regarding etiology, chronicity, and treatment use; and provide information to policy makers about allocation of resources for service delivery and research. Findings also indicate an urgent need to destigmatize DUD and educate the public, clinicians, and policy makers about its treatment to encourage affected individuals to obtain help.

Prevalence of Marijuana Use Disorders in the United States Between 2001-2002 and 2012-2013.

IMPORTANCE: Laws and attitudes toward marijuana in the United States are becoming more permissive but little is known about whether the prevalence rates of marijuana use and marijuana use disorders have changed in the 21st century. OBJECTIVE: To present nationally representative information on the past-year prevalence rates of marijuana use, marijuana use disorder, and marijuana use disorder among marijuana users in the US adult general population and whether this has changed between 2001-2002 and 2012-2013. DESIGN, SETTING, AND PARTICIPANTS: Face-to-face interviews conducted in surveys of 2 nationally representative samples of US adults: the National Epidemiologic Survey on Alcohol and Related Conditions (data collected April 2001-April 2002; N = 43,093) and the National Epidemiologic Survey on Alcohol and Related Conditions-III (data collected April 2012-June 2013; N = 36,309). Data were analyzed March through May 2015. MAIN OUTCOMES AND MEASURES: Past-year marijuana use and DSM-IV marijuana use disorder (abuse or dependence). RESULTS: The past-year prevalence of marijuana use was 4.1% (SE, 0.15) in 2001-2002 and 9.5% (SE, 0.27) in 2012-2013, a significant increase (P < .05). Significant increases were also found across demographic subgroups (sex, age, race/ethnicity, education, marital status, income, urban/rural, and region). The past-year prevalence of DSM-IV marijuana use disorder was 1.5% (0.08) in 2001-2002 and 2.9% (SE, 0.13) in 2012-2013 (P < .05). With few exceptions, increases in the prevalence of marijuana use disorder between 2001-2002 and 2012-2013 were also statistically significant (P < .05) across demographic subgroups. However, the prevalence of marijuana use disorder among marijuana users decreased significantly from 2001-2002 (35.6%; SE, 1.37) to 2012-2013 (30.6%; SE, 1.04). CONCLUSIONS AND RELEVANCE: The prevalence of marijuana use more than doubled between 2001-2002 and 2012-2013, and there was a large increase in marijuana use disorders during that time. While not all marijuana users experience problems, nearly 3 of 10 marijuana users manifested a marijuana use disorder in 2012-2013. Because the risk for marijuana use disorder did not increase among users, the increase in prevalence of marijuana use disorder is owing to an increase in prevalence of users in the US adult population. Given changing laws and attitudes toward marijuana, a balanced presentation of the likelihood of adverse consequences of marijuana use to policy makers, professionals, and the public is needed.

ADHD and the externalizing spectrum: direct comparison of categorical, continuous, and hybrid models of liability in a nationally representative sample.

PURPOSE: Alcohol use disorders, substance use disorders, and antisocial personality disorder share a common externalizing liability, which may also include attention-deficit hyperactivity disorder (ADHD). However, few studies have compared formal quantitative models of externalizing liability, with the aim of delineating the categorical and/or continuous nature of this liability in the community. This study compares categorical, continuous, and hybrid models of externalizing liability. METHOD: Data were derived from the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Seven disorders were modeled: childhood ADHD and lifetime diagnoses of antisocial personality disorder (ASPD), nicotine dependence, alcohol dependence, marijuana dependence, cocaine dependence, and other substance dependence. RESULTS: The continuous latent trait model provided the best fit to the data. Measurement invariance analyses supported the fit of the model across genders, with females displaying a significantly lower probability of experiencing externalizing disorders. Cocaine dependence, marijuana dependence, other substance dependence, alcohol dependence, ASPD, nicotine dependence, and ADHD provided the greatest information, respectively, about the underlying externalizing continuum. CONCLUSIONS: Liability to externalizing disorders is continuous and dimensional in severity. The findings have important implications for the organizational structure of externalizing psychopathology in psychiatric nomenclatures.

Comparative performance of the AUDIT-C in screening for DSM-IV and DSM-5 alcohol use disorders.

OBJECTIVE: Under the proposed DSM-5 revision to the criteria for alcohol use disorder (AUD), a substantial proportion of DSM-IV AUD cases will be lost or shifted in terms of severity, with some new cases added. Accordingly, the performance of the AUDIT-C in screening for DSM-IV AUD cannot be assumed to extend to DSM-5 AUD. The objective of this paper is to compare the AUDIT-C in screening for DSM-IV and DSM-5 AUD. METHODS: Using a broad range of performance metrics, the AUDIT-C was tested and contrasted as a screener for DSM-IV AUD (any AUD, abuse and dependence) and DSM-5 AUD (any AUD, moderate AUD and severe AUD) in a representative sample of U.S. adults aged 21 and older and among past-year drinkers. RESULTS: Optimal AUDIT-C cutpoints were identical for DSM-IV and DSM-5 AUD: ≥4 for any AUD, ≥3 or ≥4 for abuse/moderate AUD and ≥4 or ≥5 for dependence/severe AUD. Screening performance was slightly better for DSM-5 severe AUD than DSM-IV dependence but did not differ for other diagnoses. At optimal screening cutpoints, positive predictive values were slightly higher for DSM-5 overall AUD and moderate AUD than for their DSM-IV counterparts. Sensitivities were slightly higher for DSM-5 severe AUD than DSM-IV dependence. Optimal screening cutpoints shifted upwards for past-year drinkers but continued to be identical for DSM-IV and DSM-5 disorders. CONCLUSIONS: Clinicians should not face any major overhaul of their current screening procedures as a result of the DSM-5 revision and should benefit from fewer false positive screening results.

Dimensionality of DSM-IV nicotine dependence in a national sample: an item response theory application.

BACKGROUND: Research focusing on the development of a dimensional representation of DSM-IV nicotine dependence is scarce and prior research has not assessed the role of nicotine use criteria in that a dimensional representation, nor the invariance of the DSM-IV nicotine dependence criteria across important population subgroups. METHODS: Using a large, representative sample of the U.S. population, this study utilized item response theory (IRT) analyses to explore the dimensionality of DSM-IV nicotine dependence criteria and several candidate criteria for cigarette use among past-year cigarette smokers (n=10,163). RESULTS: Factor analyses demonstrated the unidimensionality of nicotine dependence criteria and IRT analyses demonstrated good fit of the observed responses and the underlying, unobserved latent trait of dependence severity. The model containing all seven DSM-IV dependence criteria, along with the consumption criterion of smoking at least a quarter of a pack of cigarettes in a day in the past year, was identified as the best-fitting model. No differential criterion functioning was shown across sex, race-ethnicity, and age subgroups. DISCUSSION: Major implications of this study are discussed in terms of the addition of a dimensional representation of nicotine dependence to pre-existing categorical representations of the disorder in the DSM-V, and the need for a nicotine consumption criterion to improve representations of nicotine dependence severity.

The role of cannabis use within a dimensional approach to cannabis use disorders.

CONTEXT: Cannabis consumption is central to diagnosis of cannabis use disorders; yet, most research on cannabis disorders has focused just on diagnosis or criteria. The present study examines the ability of a frequency and quantity measure of cannabis use as well as cannabis abuse and dependence criteria to discriminate between individuals across the cannabis use disorder continuum. METHOD: A representative sample of USA adults in 2001-2002 (N=43,093) were queried about the past year frequency of cannabis use and each Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) cannabis abuse and dependence criterion. Factor analysis and item response theory (IRT) models were used to define the relationship between observed responses and the underlying unobserved latent trait (cannabis use disorder severity) among past year cannabis users (n=1603). RESULTS: Factor analyses demonstrated a good fit for a one-factor model both with and without the cannabis use criterion and no differential criterion functioning was demonstrated across sex. The IRT model including the cannabis use criterion had discriminatory power comparable to the model without the cannabis use criterion and exceeded the informational value of the model without the cannabis use criterion in mild and moderate ranges of the severity continuum. DISCUSSION: Factor and IRT analyses disprove the validity of the DSM-IV abuse and dependence distinction: A single dimension represented the criteria rather than the two implied by the separate abuse/dependence categories. IRT models identified some dependence criteria to be among the mildest and some abuse criteria to be among the most severe--results inconsistent with the interpretation of DSM-IV cannabis abuse as a milder disorder or prodrome of cannabis dependence. The consumption criterion defined the mild end of the cannabis use disorder continuum and its excellent psychometric properties supported its consideration for inclusion in the next edition of DSM as a criterion for cannabis use disorders. Additional work is needed to identify candidate consumption criteria across all drugs that apply to the milder end of the severity continuum while also improving overall model performance and clinical diagnostic utility.

Antisocial behavioral syndromes and past-year physical health among adults in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: To describe associations of DSM-IV antisocial personality disorder (ASPD), DSM-IV conduct disorder without progression to ASPD (CD-only), and syndromal antisocial behavior in adulthood without conduct disorder before age 15 years (AABS, not a DSM-IV diagnosis) with past-year physical health status and hospital care utilization in the general U.S. adult population. METHOD: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093, response rate = 81%). Respondents were classified according to whether they met criteria for ASPD, AABS, CD-only, or no antisocial syndrome. Associations of antisocial syndromes with physical health status and care utilization were examined using normal theory and logistic regression. RESULTS: ASPD and AABS were significantly but modestly associated with total past-year medical conditions, coronary heart and gastrointestinal diseases, and numbers of inpatient hospitalizations, inpatient days, emergency department visits, and clinically significant injuries (all p < .05). ASPD was also associated with liver disease, arthritis, and lower scores on the Medical Outcomes Study 12-Item Short-Form Health Survey, version 2 (SF-12v2) physical component summary, role physical, and bodily pain scales (all p < .05). AABS was associated with noncoronary heart disease, lower scores on the SF-12v2 general health and vitality scales, and, among men, arthritis (all p < .05). CD-only was associated with single but not multiple inpatient hospitalizations, emergency department visits, and clinically significant injuries (all p < .05). CONCLUSIONS: Estimates of burden related to antisocial behavioral syndromes need to consider associated physical health problems. Prevention and treatment guidelines for injuries and common chronic diseases may need to address comorbid antisociality, and interventions targeting antisociality may need to consider general health status, including prevention and management of injuries and chronic diseases.

Antisocial personality disorder with childhood- vs. adolescence-onset conduct disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

This study, based on a nationally representative, epidemiologic sample (N = 43,093, response rate 81%), compared sociodemographic and family history correlates, antisocial personality disorder (ASPD) symptom patterns, and Axis I and Axis II comorbidity, among adults with DSM-IV ASPD who reported onset of conduct disorder (CD) in childhood ( or =age 10). Prevalence of each ASPD diagnostic criterion and comorbid lifetime disorder was estimated. Logistic regression was used to examine associations of childhood-onset CD with ASPD symptom patterns and comorbid disorders. Among the 1422 respondents with ASPD, 447 reported childhood-onset CD. Childhood-onset respondents were more likely than adolescence-onset respondents to endorse CD criteria involving aggression against persons, animals, and property before age 15, and to endorse more childhood criteria and lifetime violent behaviors. Childhood-onset respondents displayed significantly elevated odds of lifetime social phobia, generalized anxiety disorder, drug dependence, and paranoid, schizoid, and avoidant personality disorders, but significantly decreased odds for lifetime tobacco dependence. Childhood-onset CD appears to identify a more polysymptomatic and violent form of ASPD, associated with greater lifetime comorbidity for selected Axis I and Axis II disorders, in nonclinical populations.