Recreational cannabis legalization has had limited effects on a wide range of adult psychiatric and psychosocial outcomes.

BACKGROUND: The causal impacts of recreational cannabis legalization are not well understood due to the number of potential confounds. We sought to quantify possible causal effects of recreational cannabis legalization on substance use, substance use disorder, and psychosocial functioning, and whether vulnerable individuals are more susceptible to the effects of cannabis legalization than others. METHODS: We used a longitudinal, co-twin control design in 4043 twins (N = 240 pairs discordant on residence), first assessed in adolescence and now age 24-49, currently residing in states with different cannabis policies (40% resided in a recreationally legal state). We tested the effect of legalization on outcomes of interest and whether legalization interacts with established vulnerability factors (age, sex, or externalizing psychopathology). RESULTS: In the co-twin control design accounting for earlier cannabis frequency and alcohol use disorder (AUD) symptoms respectively, the twin living in a recreational state used cannabis on average more often (ßw = 0.11, p = 1.3 × 10-3), and had fewer AUD symptoms (ßw = -0.11, p = 6.7 × 10-3) than their co-twin living in an non-recreational state. Cannabis legalization was associated with no other adverse outcome in the co-twin design, including cannabis use disorder. No risk factor significantly interacted with legalization status to predict any outcome. CONCLUSIONS: Recreational legalization was associated with increased cannabis use and decreased AUD symptoms but was not associated with other maladaptations. These effects were maintained within twin pairs discordant for residence. Moreover, vulnerabilities to cannabis use were not exacerbated by the legal cannabis environment. Future research may investigate causal links between cannabis consumption and outcomes.

Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design.

Background: As more states pass recreational cannabis legalization (RCL), we must understand how RCL affects substance use.Objectives: The current study aims to examine the effect of RCL on lifetime and past-year use of cannabis, alcohol, tobacco, and other drugs, frequency of cannabis, alcohol, and tobacco use, co-use of cannabis with alcohol and tobacco, and consequences from cannabis and alcohol use.Methods: We used a unique, co-twin control design of twin pairs who were discordant for living in a state with RCL between 2018 and 2021. The sample consisted of 3,830 adult twins (41% male), including 232 twin pairs discordant for RCL. Problems from alcohol and cannabis use were assessed via the Brief Marijuana Consequences Questionnaire and the Brief Young Adult Alcohol Consequences Questionnaire.Results: Results indicated that the twin living in an RCL state was more likely to endorse past-year cannabis use (OR = 1.56, p = .009), greater number of cannabis use days in the past 6 months (ß = 0.47, p = .019), but not more negative consequences from cannabis use (ß = 0.21, p = .456) compared to their co-twin in a non-RCL state. There were no differences within-twin pairs in frequency of alcohol use (ß=-0.05, p = .601), but the RCL twin reported fewer negative consequences from alcohol use (ß=-0.29, p = .016) compared to their co-twin in a non-RCL state. We did not observe any other differences within-twin pairs on other outcomes.Conclusion: These results suggest that living in an RCL state is associated with greater cannabis frequency but not more negative consequences from cannabis use than living in a non-RCL state.

Addendum to "Evaluating substance use outcomes of recreational cannabis legalization using a unique co-twin control design".

An earlier version of this article was published in error. Our prior publication was missing reference to a prior study on this topic. Our prior research has not found an association between recreational cannabis legalization (RCL) and negative psychosocial and psychiatric outcomes. We reported significant associations between RCL with greater cannabis frequency and fewer alcohol use disorder symptoms. The current study expands on our previous research by using a cross-sectional design and different measures of problems from cannabis and alcohol use and including additional substance use variables. The current study found similar results to our previous research.

Adolescents in Treatment for Substance Use Disorders: Callous-Unemotional Traits Moderate Associations Between Transdiagnostic Symptoms and Adolescent Suicidality.

Suicide, a common cause of death in adolescents, is linked to internalizing and externalizing symptoms. These associations are pronounced amongst adolescents who use substances. But these relationships are complex. For example, sex differences are present in association with internalizing/externalizing symptoms as well as differences in suicidality. A rarely explored factor that may account for this complexity as a moderator is callous-unemotional traits. The present study examines associations of internalizing and externalizing in relation to suicidality in the context of callous-unemotional traits amongst adolescents in substance use treatment. Additionally, sex differences were explored. A sample of 317 adolescents (13-18; 16.05 ± 1.22) in treatment for substance use completed measures for internalizing, externalizing, and suicidal symptoms. The main result suggested the presence of callous-unemotional (CU) traits attenuated the positive association between internalizing and a latent suicidality factor. This novel result contextualizes the association between transdiagnostic symptoms and suicidality. Assessing CU traits in the presence of internalizing symptoms may be an important component of understanding suicide risk amongst adolescents in treatment for substance use.

The association between saving disposition and financial distress: A genetically informed approach.

Saving disposition, the tendency to save rather than consume, has been found to be associated with economic outcomes. People lacking the disposition to save are more likely to experience financial distress. This association could be driven by other economic factors, behavioral traits, or even genetic effects. Using a sample of 3,920 American twins, we develop scales to measure saving disposition and financial distress. We find genetic influences on both traits, but also a large effect of the rearing family environment on saving disposition. We estimate that 44% of the covariance between the two traits is due to genetic effects. Saving disposition remains strongly associated with lower financial distress, even after controlling for family income, cognitive ability, and personality traits. The association persists within families and monozygotic twin pairs; the twin who saves more tends to be the twin who experiences less financial distress. This result suggest that there is a direct association between saving disposition and financial distress, although the direction of causation remains unclear.

The impact of recreational cannabis legalization on youth: the Colorado experience.

Over the past two decades, cannabis policies have liberalized in the United States, culminating in the legalization of recreational cannabis in Colorado and Washington state in 2012. This review will focus on the impact of recreational cannabis legalization in Colorado. While the prevalence of past-year and past-month cannabis use has remained relatively steady among adolescents post-legalization, the prevalence of young adult use has continued to rise. Cannabis products with increased potency have become more prevalent and widely used. There are concerns that the use of products with increased potency will increase risk for cannabis use and comorbid mental health disorders, particularly cannabis-induced psychosis and suicidal behavior, although more research is needed to fully understand the impact of high-potency products. Since the legalization of recreational cannabis, numerous additional public health concerns have emerged: unintentional overdoses requiring acute care visits, electronic vaping-associated lung injury, increased motor vehicle collisions related to cannabis consumption, and higher rates of cannabis use during pregnancy. Lessons learned from the first decade of cannabis legalization emphasize the need for research efforts to provide evidence-based guidelines, inform prevention strategies, and implement selective interventions for at-risk populations including youth, individuals with comorbid mental health disorders, and individuals who are pregnant.

Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.

The Void in Clinician Counseling of Cannabis Use.

As more states legalize cannabis for medical use, people increasingly use cannabis to treat medical conditions. Well-documented harms of cannabis use include increased risk of fatal auto accidents, neurocognitive deficits, and increased risk of addiction. Observational data supports the use of cannabis for pain, nausea and vomiting related to chemotherapy, and multiple sclerosis spasticity symptoms. Given potential harms versus benefits of cannabis use, how should physicians counsel patients regarding their cannabis use? This paper briefly reviews the evidence supporting medical cannabis use for pain. We consider cannabis use as a harm reduction strategy for pain management. We encourage routine, longitudinal assessments of cannabis use among patients. We discuss the commercialization of cannabis for financial gain, contributing to potent and addictive cannabis. We highlight the concerning phenomena of cannabis dispensary workers as proxy clinicians. Finally, we present three strategies to reduce public harms associated with potent cannabis use including required testing and reporting of tetrahydrocannabinol/cannabidiol concentrations, rigorous study of high-potency cannabis available for purchase in dispensaries across the USA, and large-scale efforts to measure cannabis consumption in medical records so prospective, longitudinal studies can be conducted to correlate consumption measures with medical and psychiatric outcomes.

Adolescent Externalizing Psychopathology and Its Prospective Relationship to Marijuana Use Development from Age 14 to 30: Replication Across Independent Longitudinal Twin Samples.

Externalizing psychopathology in early adolescence is a highly heritable risk factor for drug use, yet how it relates to marijuana use development is not well-characterized. We evaluate this issue in independent twin samples from Colorado (N = 2608) and Minnesota (N = 3630), assessed from adolescence to early adulthood. We used a biometric latent growth model of marijuana use frequency with data from up to five waves of assessment from ages 14 to 30, to examine change in marijuana use and its relationship with a factor model of adolescent externalizing psychopathology. The factor structure of adolescent externalizing psychopathology was similar across samples, as was the association between that common factor and early marijuana use (Minnesota r = 0.67 [0.60, 0.75]; Colorado r = 0.69 [0.59, 0.78]), and increase in use (Minnesota r = 0.18 [0.10, 0.26]; Colorado r = 0.20 [0.07, 0.34]). Early use was moderately heritable in both samples (Minnesota h2 = 0.57 [0.37, 0.79]; Colorado h2 = 0.42 [0.14, 0.73]). Increase in use was highly heritable in Minnesota (h2 = 0.82 [0.72, 0.88]), less so in Colorado (h2 = 0.22 [0.01, 0.66]), and shared environmental effects were larger in Colorado (c2 = 0.55 [0.14, 0.83]) than Minnesota (c2 = 0 [0, 0.06]). We found moderate genetic correlations between externalizing psychopathology and early use in both samples. Finally, additional analyses in the Minnesota sample indicated that marijuana use decreased during the late 20s. This decline is strongly heritable (h2 = 0.73 [0.49, 0.91]) and moderately negatively correlated with adolescent externalizing psychopathology (r = - 0.41 [- 0.54, - 0.28]). Adolescent externalizing psychopathology is genetically correlated with change in late adolescent marijuana use (late teens, early 20s), as well as maintenance of use in early adulthood (late 20 s) even after controlling for the effects of early use.

Opioid and non-opioid utilization at home following gastrointestinal procedures: a prospective cohort study.

BACKGROUND: Overprescribing of opioid medications for patients to be used at home after surgery is common. We sought to ascertain important patient and procedural characteristics that are associated with low versus high rates of self-reported utilization of opioids at home, 1-4 weeks after discharge following gastrointestinal surgery. METHODS: We developed a survey consisting of questions from NIH PROMIS tools for pain intensity/interference and queries on postoperative analgesic use. Adult patients completed the survey weekly during the first month after discharge. Using regression procedures we determined the patient and procedure characteristics that predicted high post-discharge opioid use operationalized as 75 mg oral morphine equivalents/50 mg oxycodone reported taken. RESULTS: The survey response rate was 86% (201/233). High opioid use was reported by 52.7% of patients (106/201). Median reported intake of opioid pain pills was 7 for week #1 and 0 for weeks #2-4. Combinations of acetaminophen and non-steroidal and anti-inflammatory drugs were used by 8.9%-12.5% of patients after discharge. Following adjustment for significant variables of the univariate analysis, last 24-h in-hospital opioid intake remained as a significant co-variate for post-discharge opioid intake. CONCLUSIONS: After gastrointestinal surgery, the equivalent of each oxycodone 5 mg tablet taken in the last 24 h before discharge increases the likelihood of taking the equivalent of > 10 oxycodone 5 mg tablets by 5%. Non-opioid analgesia was utilized in less than half of the cases. Maximizing non-opioid analgesic therapy and basing opioid prescriptions on 24-h pre-discharge opioid intake may improve the quality of post-discharge pain management.

Cannabis Oil Use by Adolescents and Young Adults With Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to describe use of oral or sublingual cannabis oil (CO) by adolescent and young adult patients with inflammatory bowel disease (IBD). METHODS: A descriptive study of IBD patients 13 to 23 years of age seen between January 2015 through December 2017 at Children's Hospital Colorado. Information obtained included chart abstraction, electronic and interview self-report, and serum cannabinoid levels. We compared CO users and cannabis non-users for clinical characteristics and perceptions of risk. Users of CO provided information on routes, patterns, motivations, and perceived benefits and problems with use. RESULTS: The 15 users and 67 non-users were similar for clinical characteristics and pain and appetite scores. 9 of 15 (60%) CO users had used in the past 30 days, an average of 22 ±â€Š9 times; and 4 used daily. A variety of strengths and CBD:THC ratios were reported. Most common perceived effect of use was on sleep quality, nausea, and increase in appetite. Of the 15 users, 6 used only CO and no additional forms of cannabis. Of these 6 CO only users, 5 reported a medical reason for use, most commonly to relieve pain. CONCLUSIONS: Adolescent and young adults with IBD used oral CO and many used other cannabis products as well. Users perceived some medical benefit. Care teams should strive for open communication about use until further information on safety and efficacy becomes available.

Marijuana Use by Adolescents and Young Adults with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD). STUDY DESIGN: This descriptive cross-sectional study of patients seen between December 2015 through June 2017 at Children's Hospital Colorado for IBD enrolled patients 13-23 years of age, independent of marijuana use status. Information obtained consisted of chart review, electronic and interview self-report, and serum cannabinoid levels. Marijuana ever-users were compared with never-users for clinical characteristics and perceptions of risk with use; users provided information on routes, patterns, motivations, and perceived benefits and problems with use. RESULTS: Of 99 participants, ever-use was endorsed by 32% (32 of 99) and daily or almost daily use by 9% (9 of 99). Older age was the only characteristic related to endorsing marijuana use. Twenty-nine ever-users completed all questionnaires. After adjusting for age, users were 10.7 times more likely to perceive low risk of harm with regular use (P < .001). At least 1 medical reason for use was endorsed by 57% (17 of 30), most commonly for relief of physical pain (53%, 16 of 30) (2 did not complete all questionnaires). Problems from use were identified by 37% (11 of 30), most commonly craving/strong urge to use. Most common route of use was smoking (83%) followed by edibles (50%), dabbing (40%), and vaping (30%). CONCLUSIONS: Marijuana use by adolescents and young adults with IBD is common and perceived as beneficial. Guidelines for screening, testing, and counseling of marijuana use should be developed for patients with IBD.

Impulsivity Dimensions and Risky Sex Behaviors in an At-Risk Young Adult Sample.

Impulsivity is a personality-based risk factor that has been well studied in relation to risky sexual behavior. Recent conceptualizations of impulsivity have proposed multidimensional facets comprised of premeditation, perseverance, sensation seeking, negative urgency, and positive urgency (UPPS-P model). Prior studies have found that these facets are associated with risky sexual behavior in adolescent and college student samples, but no prior studies have evaluated them in clinical samples. The current study examined how impulsivity-related traits related to two different risky sexual behaviors in a clinical sample of at-risk young adults who had both conduct disorder and substance use disorder symptoms as adolescents (n = 529). Lack of premeditation was also tested as a moderator of the relationship between facets of impulsivity and both risky sex outcomes. Results demonstrated that sensation seeking, negative urgency, and positive urgency were correlated with risky sex behaviors. Additionally, multiple regression analyses indicated that sensation seeking was uniquely associated with the number of sexual partners in the past 5 years, whereas positive urgency was uniquely associated with unprotected sex while under the influence. Finally, a significant interaction between lack of premeditation and negative urgency suggests that at-risk young adults with both high negative urgency and lack of premeditation were the likeliest to have the most sexual partners in the past 5 years. This study adds to the current understanding of the relationship between reward- and affect-driven facets of impulsivity and risky sexual behaviors and may lend utility to the development of interventions for at-risk populations.

Positive expectancies mediate the association between sensation seeking and marijuana outcomes in at-risk young adults: A test of the acquired preparedness model.

BACKGROUND AND OBJECTIVES: The acquired preparedness model (APM) integrates personality trait research and psychosocial learning, which are theorized to ultimately increase risk for problematic substance use outcomes. METHODS: The present study uses the APM to examine the potential mediational role of positive and negative expectancies on the relationship between impulsivity and two marijuana outcomes (ie, frequency of use and marijuana use disorder [MUD] symptom count) among an at-risk sample of young adults with history of antisocial behavior and substance use in adolescence and their siblings (n = 312). RESULTS: Results suggest a significant indirect effect of sensation seeking on recent marijuana use through positive marijuana expectancies. There also was a significant indirect effect of sensation seeking on past-year MUD symptoms through positive expectancies. No significant indirect effects through negative expectancies were found for either outcome. DISCUSSION AND CONCLUSIONS: Our findings are consistent with the APM and suggest that higher sensation seeking is related to increased positive beliefs about marijuana outcomes, which is related to higher marijuana use and more MUD symptoms. SCIENTIFIC SIGNIFICANCE: These findings suggest that positive expectancies are an important risk factor for marijuana use and misuse, particularly for at-risk individuals with elevated rates of sensation seeking. Positive marijuana expectancies may be important to address in interventions for at-risk individuals. (Am J Addict 2018;XX:1-6).

Phenotypic and Genetic Relationship Between BMI and Drinking in a Sample of UK Adults.

The health impairments derived from both alcoholism and obesity are well known. However, reports that relate increased alcohol use with increased measures of obesity have been mixed in their findings, especially with respect to genetic factors that could potentially link these two behaviors. Here, using a large sample of adults from the UK (n ≈ 113,000), we report both the observed and genetic correlations between BMI (kg/m2) and two measures of alcohol use: reported quantity (drinks per week) and frequency of use (from never to daily). Overall, both observationally and genetically, alcohol intake is negatively correlated with BMI. Phenotypic correlations ranged from -0.01 to -0.17, and genetic correlations ranged from -0.1 to -0.4. Genetic correlations tended to be stronger than the phenotypic correlations, and these correlations were stronger in females and between BMI and, specifically, frequency of use. Though the mechanisms driving these relationships are yet to be identified, we can conclude that the genetic factors related to drinking both more and more often are shared with those responsible for lower BMI.

An Atmospheric Pressure Chemical Ionization MS/MS Assay Using Online Extraction for the Analysis of 11 Cannabinoids and Metabolites in Human Plasma and Urine.

BACKGROUND: Although, especially in the United States, there has been a recent surge of legalized cannabis for either recreational or medicinal purposes, surprisingly little is known about clinical dose-response relationships, pharmacodynamic and toxicodynamic effects of cannabinoids such as Δ9-tetrahydrocannabinol (THC). Even less is known about other active cannabinoids. METHODS: To address this knowledge gap, an online extraction, high-performance liquid chromatography coupled with tandem mass spectrometry method for simultaneous quantification of 11 cannabinoids and metabolites including THC, 11-hydroxy-Δ9-tetrahydrocannabinol, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid, 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid glucuronide (THC-C-gluc), cannabinol, cannabidiol, cannabigerol, cannabidivarin, Δ9-tetrahydrocannabivarin (THCV), and 11-nor-9-carboxy-Δ9-tetrahydrocannabivarin (THCV-COOH) was developed and validated in human urine and plasma. RESULTS: In contrast to atmospheric pressure chemical ionization, electrospray ionization was associated with extensive ion suppression in plasma and urine samples. Thus, the atmospheric pressure chemical ionization assay was validated showing a lower limit of quantification ranging from 0.39 to 3.91 ng/mL depending on study compound and matrix. The upper limit of quantification was 400 ng/mL except for THC-C-gluc with an upper limit of quantification of 2000 ng/mL. The linearity was r > 0.99 for all analyzed calibration curves. Acceptance criteria for intrabatch and interbatch accuracy (85%-115%) and imprecision (<15%) were met for all compounds. In plasma, the only exceptions were THCV (75.3%-121.2% interbatch accuracy) and cannabidivarin (interbatch imprecision, 15.7%-17.2%). In urine, THCV did not meet predefined acceptance criteria for intrabatch accuracy. CONCLUSIONS: This assay allows for monitoring not only THC and its major metabolites but also major cannabinoids that are of interest for marijuana research and clinical practice.

Unique and interactive effects of impulsivity facets on reckless driving and driving under the influence in a high-risk young adult sample.

Risky driving behaviors are disproportionately high among young adults and impulsivity is a robust risk factor. Recent conceptualizations have proposed multidimensional facets of impulsivity comprised of negative urgency, premeditation, perseverance, sensation seeking, and positive urgency (UPPS-P model). Prior studies have found these facets are associated with risky driving behaviors in college student samples, but no prior studies have examined these facets in clinical samples. This study examined the unique and interactive effects of UPPS-P impulsivity facets on past-year risky driving behaviors in a sample of high-risk young adults (ages 18-30 years) with a history of substance use and antisocial behavior and their siblings (n=1,100). Multilevel Poisson regressions indicated that sensation seeking and negative urgency were uniquely and positively associated with both frequency of past-year reckless driving and driving under the influence. Moreover, lack of premeditation was uniquely and positively associated with reckless driving, whereas lack of perseverance was uniquely and positively associated with driving under the influence. Furthermore, lack of premeditation moderated and strengthened the positive association between sensation seeking and driving under the influence. These study findings suggest that assessing multiple facets of trait impulsivity could facilitate targeted prevention efforts among young adults with a history of externalizing psychopathology.

Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence.

Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence. The capture, sequencing, and analysis of all variants in 16 CHRN genes (CHRNA1-7, 9, 10, CHRNB1-4, CHRND, CHRNG, CHRNE) were performed independently for each subject in each sample. Sequencing reads were aligned to the human reference sequence using BWA prior to variant calling with the Genome Analysis ToolKit (GATK). Low frequency variants (minor allele frequency < 0.05) were analyzed using SKAT-O and C-alpha to examine the distribution of rare variants among cases and controls. In our larger sample, the region containing the CHRNA6/CHRNB3 gene cluster was significantly associated with disease status using both SKAT-O and C-alpha (unadjusted p values <0.05). More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. These data support a role for genetic variants in CHRN genes and antisocial drug behaviors.

Adolescent Male Conduct-Disordered Patients in Substance Use Disorder Treatment: Examining the "Limited Prosocial Emotions" Specifier.

To our knowledge, this is the first study to examine the DSM-5-defined conduct disorder (CD) with limited prosocial emotions (LPE) among adolescents in substance use disorder (SUD) treatment, despite the high rates of CD in this population. We tested previously published methods of LPE categorization in a sample of male conduct-disordered patients in SUD treatment (n=196). CD with LPE patients did not demonstrate a distinct pattern in terms of demographics or co-morbidity regardless of the categorization method utilized. In conclusion, LPE, as operationalized here, does not identify a distinct subgroup of patients based on psychiatric comorbidity, SUD diagnoses, or demographics.

Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample.

Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10(-6)). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.