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When presented with decisions that require simultaneously weighing self-benefit and other harm, adolescents with callous-unemotional traits compared with controls engage in less Costly Helping (i.e., giving up a benefit to protect a beneficent other). Young adults completed questionnaires, played an online-administered game of Costly Helping, and viewed an Elevation stimulus video (when witnessing another’s act of virtue, individuals may experience a positive or elevating response). Subjects were assigned to one of four study arms, which varied the order of presentation. Higher levels of Factor 1 (callousness) psychopathic trait scale scores (assessed using the Levenson Self-Report Psychopathy Scale) were associated with significantly less Costly Helping. Elevation associated positively with Costly Helping behaviors and negatively with psychopathic traits. Introducing Elevation as an independent variable in regression analyses attenuated the relationship between psychopathic traits and Costly Helping, suggesting mediation. Those viewing the Elevation stimulus video prior to playing the game, as opposed to after, trended toward more Costly Helping by taking less money for themselves ($3.28 vs. $3.72). Results support that this simple game provides meaningful behavioral data associated with psychopathic traits. Differences in Elevation may, in part, explain the observed differences in prosocial behavior in those with high psychopathic traits.

BACKGROUND AND AIMS: Adolescents with conduct and substance use problems are at increased risk for premature mortality, but the extent to which these risk factors reflect family- or individual-level differences and account for shared or unique variance is unknown. This study examined common and independent contributions to mortality hazard in adolescents ascertained for conduct disorder (CD) and substance use disorder (SUD), their siblings and community controls, hypothesizing that individual differences in CD and SUD severity would explain unique variation in mortality risk beyond that due to clinical/control status and demographic factors. DESIGN: Mortality analysis in a prospective study (Genetics of Antisocial Drug Dependence Study) that began in 1993. Multi-site sample recruited in San Diego, California and Denver, Colorado, USA. PARTICIPANTS: A total of 1463 clinical probands were recruited through the juvenile correctional system, court-mandated substance abuse treatment programs and correctional schools, along with 1399 of their siblings, and 904 controls. MEASUREMENTS: Mortality and cause-of-death were assessed via National Death Index search (released October, 2017). FINDINGS: There were 104 deaths documented among 3766 (1168 female) adolescents and young adults (average age 16.79 years at assessment, 32.69 years at death/censoring). Mortality hazard for clinical probands and their siblings was 4.99 times greater than that of controls (95% confidence interval = 2.40-10.40; P

To evaluate marijuana use by adolescents and young adults with inflammatory bowel disease (IBD).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.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%).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.

PURPOSE: Although cesarean delivery is the most common surgical procedure in the United States, postoperative opioid prescribing varies greatly. We hypothesized that patient characteristics, procedural characteristics, or both would be associated with high vs low opioid use after discharge. This information could help individualize prescriptions. METHODS: In this prospective cohort study, we quantified opioid use for 4 weeks following hospital discharge after cesarean delivery. Predischarge characteristics were obtained from health records, and patients self-reported total opioid use postdischarge on weekly questionnaires. Opioid use was quantified in milligram morphine equivalents (MMEs). Binomial and Poisson regression analyses were performed to assess predictors of opioid use after discharge. RESULTS: Of the 233 patients starting the study, 203 (87.1%) completed at least 1 questionnaire and were included in analyses (86.3% completed all 4 questionnaires). A total of 113 patients were high users (>75 MMEs) and 90 patients were low users (≤75 MMEs) of opioids postdischarge. The group reporting low opioid use received on average 44% fewer opioids in the 24 hours before discharge compared with the group reporting high opioid use (mean = 33.0 vs 59.3 MMEs, P

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 ± 9 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.

To our knowledge, this is the first study to examine the Diagnostic and Statistical Manual of Mental Disorders (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 comorbidity 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.

BACKGROUND: Knowledge of incidence and risk factors for long-term opioid prescribing is critical for surgical patients. In this retrospective cohort study, we linked information available at the time of surgery with prescription data to ascertain characteristics associated with prolonged opioid therapy. METHODS: Patients (n=6,003) with claims in the Colorado All Payer Claims Database (APCD) were matched with 20,501 encounters in a clinical database. Rates of prescription filling were defined by at least one monthly opioid claim relative to the date of surgery. Associations of variables with claims during months 2-6 post-operatively (“long-term prescription filling”) were evaluated, and significant variables were jointly modeled using binomial regression. RESULTS: Rates of patients filling opioid prescriptions preoperatively [month (M) relative to date of surgery] were 22%(-3M), 24%(-2M), and 27%(-1M); after surgery, opioid fill rates were 62%(1M), 28%(2M), 24%(3), 24%(4M), 23%(5M), and 22%(6M). The majority, 71-76%, of patients filling prescriptions in months 2-6 after surgery had also filled before surgery. In the binomial regression model, long-term opioid use was associated with prior opioid use (p

Adolescents with conduct and substance use problems are at increased risk for premature mortality, but the extent to which these risk factors reflect family- or individual-level differences and account for shared or unique variance is unknown. This study examined common and independent contributions to mortality hazard in adolescents ascertained for conduct disorder (CD) and substance use disorder (SUD), their siblings and community controls, hypothesizing that individual differences in CD and SUD severity would explain unique variation in mortality risk beyond that due to clinical/control status and demographic factors.Mortality analysis in a prospective study (Genetics of Antisocial Drug Dependence Study) that began in 1993.Multi-site sample recruited in San Diego, California and Denver, Colorado, USA.A total of 1463 clinical probands were recruited through the juvenile correctional system, court-mandated substance abuse treatment programs and correctional schools, along with 1399 of their siblings, and 904 controls.Mortality and cause-of-death were assessed via National Death Index search (released October, 2017).There were 104 deaths documented among 3766 (1168 female) adolescents and young adults (average age 16.79 years at assessment, 32.69 years at death/censoring). Mortality hazard for clinical probands and their siblings was 4.99 times greater than that of controls (95% confidence interval = 2.40-10.40; P 0.001). After accounting for demographic characteristics, site, clinical status, familial dependence and shared contributions of CD and SUD, CD independently predicted mortality hazard, whereas SUD severity did not.In the United States, youth with conduct and substance use disorders and their siblings face far greater risk of premature death than demographically similar community controls. In contrast to substance use disorder severity, conduct disorder is a robust predictor of unique variance in all-cause mortality hazard beyond other risk factors.

Perspectives of adolescent research participants regarding conflicts of interest (COIs) and their impact on trust in researchers have not been studied. This study evaluates views of adolescent patients in treatment for substance and conduct problems compared to controls enrolled in genomic addiction research.Participants included 273 (190 patients, 83 controls) adolescents. Participants consented or assented (with parental consent) to have their genomic information deposited in a NIH biobank that shares information globally with qualified investigators. As part of that study, participants completed a COI survey. Endorsement of each COI item was analyzed with multiple logistic regressions, evaluating group, age, sex, ethnicity, and highest grade completed.Patients and controls differed in gender, ethnicity and highest grade completed. In response to the survey, 38.4% of patients and 25.3% of controls "want to know" and 35.3% of patients and 37.3% of controls "might want to know" about COIs. Males were less likely to want/might want disclosure about COIs. Older patients were more likely to want disclosure about financial interests; patients were more likely to want disclosure about possible treatments; males were more likely to want information about monetary gains. Both groups requested between 1 paragraph and 1 page of information. Disclosure of COIs did not impact trust for most participants.Adolescent patients and controls in this study want comparable information for disclosure of COIs including monetary gains, salary, publications, grants, and professional awards. Notably, the majority of patients and controls report that disclosure will not undermine trust in researchers.

We sought to identify brain activation differences in conduct-problem youth with limited prosocial emotions (LPE) compared to conduct-problem youth without LPE and community adolescents, and to test associations between brain activation and severity of callous-unemotional traits. We utilized a novel task, which asks subjects to repeatedly decide whether to accept offers where they will benefit but a beneficent other will be harmed. Behavior on this task has been previously associated with levels of prosocial emotions and severity of callous-unemotional traits, and is related to empathic concern. During fMRI acquisition, 66 male adolescents (21 conduct-problem patients with LPE, 21 without, and 24 typically-developing controls) played this novel game. Within typically-developing controls, we identified a network engaged during decision involving bilateral insula, and inferior parietal and medial frontal cortices, among other regions. Group comparisons using non-parametric (distribution-free) permutation tests demonstrated LPE patients had lower activation estimates than typically-developing adolescents in right anterior insula. Additional significant group differences emerged with our a priori parametric cluster-wise inference threshold. These results suggest measurable functional brain activation differences in conduct-problem adolescents with LPE compared to typically-developing adolescents. Such differences may underscore differential treatment needs for conduct-problem males with and without LPE.

BACKGROUND: Some conduct-disordered youths have high levels of callous unemotional traits and meet the DSM-5's "with limited prosocial emotions" (LPE) specifier. These youths often do aggressive, self-benefitting acts that cost others. We previously developed a task, the AlAn's game, which asks participants to repeatedly decide whether to accept or reject offers in which they will receive money but a planned charity donation will be reduced. In our prior work, more "costly helping" (i.e., rejecting the offered money and protecting the donation) was associated with lower callous unemotional traits. Here we extend that prior work in a larger sample of adolescent male patients with serious conduct problems and controls, and test whether this association is mediated specifically by a Moral Elevation response (i.e., a positive emotional response to another's act of virtue). METHODS: The adolescent male participants were: 45 patients (23 with LPE) and 26 controls, who underwent an extensive phenotypic assessment including a measure of Moral Elevation. About 1 week later participants played the AlAn's game. RESULTS: All AlAn's game outcomes demonstrated significant group effects: (1) money taken for self (p = 0.02); (2) money left in the charitable donation (p = 0.03); and, (3) costly helping (p = 0.047). Controls took the least money and did the most costly helping, while patients with LPE took the most money and did the least costly helping. Groups also significantly differed in post-stimulus Moral Elevation scores (p = 0.005). Exploratory analyses supported that the relationship between callous unemotional traits and costly helping on the AlAn's game may be mediated in part by differences in Moral Elevation. CONCLUSIONS: The AlAn's game provides a standardized behavioral measure associated with callous unemotional traits. Adolescents with high levels of callous unemotional traits engage in fewer costly helping behaviors, and those differences may be related to blunting of positive emotional responses. Language: en

a b s t r a c t Boys with serious conduct and substance problems (Antisocial Substance Dependence (ASD)) repeat- edly make impulsive and risky decisions in spite of possible negative consequences. Because prefrontal cortex (PFC) is involved in planning behavior in accord with prior rewards and punishments, structural abnormalities in PFC could contribute to a person's propensity to make risky decisions. Methods: We acquired high-resolution structural images of 25 male ASD patients (ages 14-18 years) and 19 controls of similar ages using a 3 T MR system. We conducted whole-brain voxel-based morphome- tric analysis (p < 0.05, corrected for multiple comparisons at whole-brain cluster-level) using Statistical Parametric Mapping version-5 and tested group differences in regional gray matter (GM) volume with analyses of covariance, adjusting for total GM volume, age, and IQ; we further adjusted between-group analyses for ADHD and depression. As secondary analyses, we tested for negative associations between GM volume and impulsivity within groups and separately, GM volume and symptom severity within patients using whole-brain regression analyses. Results: ASD boys had significantly lower GM volume than controls in left dorsolateral PFC (DLPFC), right lingual gyrus and bilateral cerebellum, and significantly higher GM volume in right precuneus. Left DLPFC GM volume showed negative association with impulsivity within controls and negative association with substance dependence severity within patients. Conclusions: ASD boys show reduced GM volumes in several regions including DLPFC, a region highly rele- vant to impulsivity, disinhibition, and decision-making, and cerebellum, a region important for behavioral regulation, while they showed increased GM in precuneus, a region associated with self-referential and self-centered thinking. © 2011 Elsevier Ireland Ltd. All rights reserved.

Objective This study assessed whether a customized disclosure form increases understanding for adolescents with substance use disorder (SUD) when compared to a standard disclosure for genomic addiction research. Method We gathered empirical data from adolescents with SUD, family members, former patients followed since adolescence, and community counterparts. The study was conducted in four stages. Stage 1: national experts ( n = 32) identified current, future, speculative risks of broadly shared biobanks. Stage 2 assessed participants’ ( n = 181) understanding of current risks as a prerequisite for rating saliency of risks via a Visual Analog Scale. Salient risks were incorporated into a customized disclosure form. Stage 3 compared the understanding of customized disclosure by participants ( n = 165) at baseline; all groups scored comparably. Stage 4 conducted a direct comparison of the standard disclosure to standard disclosure plus customized disclosure ( n = 195). Independent t -tests compared understanding in those receiving the standard disclosure to standard disclosure plus customized disclosure within 6 groups. Results The customized disclosure significantly improved understanding in adolescent patients ( p = 0.002) and parents of patients ( p = 0.006) to the level of their counterparts. The customized disclosure also significantly improved understanding in siblings of former patients ( p = 0.034). Understanding of standard disclosure in patients versus controls was significantly different ( p = 0.005). The groups receiving the customized disclosure scored significantly higher. Understanding of the standard disclosure plus customized disclosure in patients versus controls was not significantly different. Conclusion Adolescents with addictions understand the risks of participating in genomic addiction research as well as their community counterparts when information provided is salient to them.

This study surveyed all adolescents who were enrolled in behavioral genomic research and provided DNA to a biobank, including 320 patients undergoing treatment for substance and conduct problems (SCPs) and 109 non-SCP controls. Participants selected from three options on the return of individual genomic results (RIR) and rated eight methods of re-contact. Most individuals with SCPs (77.8%) and non-SCP controls (72.5%) wanted RIR involving health or behavioral implications. The majority of individuals with SCPs (67.2%) and non-SCP controls (69.7%) indicated that phone re-contact was 'best', with e-mail (22.5% SCPs, 33.9% non-SCPs) and social networking websites (21.3% SCPs, 20.2% non-SCPs) being viable options. These results suggest a layered approach for RIR: phone calls, followed by e-mails and a secure message to a social networking account. Data from this special and vulnerable population, which includes youth involved in the criminal justice system and substantial minority participation, bring an essential and missing perspective to the discussion of RIR.

Objective Structural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Hypotheses: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum). Methods We conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p

BackgroundAccidental injury and homicide, relatively common among adolescents, often follow risky behaviors; those are done more by boys and by adolescents with greater behavioral disinhibition (BD).HypothesisNeural processing during adolescents' risky decision-making will differ in youths with greater BD severity, and in males vs. females, both before cautious behaviors and before risky behaviors.Methodology/principal findings81 adolescents (PATIENTS with substance and conduct problems, and comparison youths (Comparisons)), assessed in a 2 x 2 design (PatientsComparisons x Male:Female) repeatedly decided between doing a cautious behavior that earned 1 cent, or a risky one that either won 5 or lost 10 cents. Odds of winning after risky responses gradually decreased. Functional magnetic resonance imaging captured brain activity during 4-sec deliberation periods preceding responses. Most neural activation appeared in known decision-making structures. PATIENTS, who had more severe BD scores and clinical problems than Comparisons, also had extensive neural hypoactivity. Comparisons' greater activation before cautious responses included frontal pole, medial prefrontal cortex, striatum, and other regions; and before risky responses, insula, temporal, and parietal regions. Males made more risky and fewer cautious responses than females, but before cautious responses males activated numerous regions more than females. Before risky behaviors female-greater activation was more posterior, and male-greater more anterior.Conclusions/significanceNeural processing differences during risky-cautious decision-making may underlie group differences in adolescents' substance-related and antisocial risk-taking. Patients reported harmful real-life decisions and showed extensive neural hypoactivity during risky-or-cautious decision-making. Males made more risky responses than females; apparently biased toward risky decisions, males (compared with females) utilized many more neural resources to make and maintain cautious decisions, indicating an important risk-related brain sexual dimorphism. The results suggest new possibilities for prevention and management of excessive, dangerous adolescent risk-taking.

Adolescents with substance use disorder (SUD) and conduct problems exhibit high levels of impulsivity and poor self-control. Limited work to date tests for brain cortical thickness differences in these youths.To investigate differences in cortical thickness between adolescents with substance use and conduct problems and controls.We recruited 25 male adolescents with SUD, and 19 male adolescent controls, and completed structural 3T magnetic resonance brain imaging. Using the surface-based morphometry software FreeSurfer, we completed region-of-interest (ROI) analyses for group cortical thickness differences in left, and separately right, inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and insula. Using FreeSurfer, we completed whole-cerebrum analyses of group differences in cortical thickness.Versus controls, the SUD group showed no cortical thickness differences in ROI analyses. Controlling for age and IQ, no regions with cortical thickness differences were found using whole-cerebrum analyses (though secondary analyses co-varying IQ and whole-cerebrum cortical thickness yielded a between-group cortical thickness difference in the left posterior cingulate/precuneus). Secondary findings showed that the SUD group, relative to controls, demonstrated significantly less rightleft asymmetry in IFG, had weaker insular-to-whole-cerebrum cortical thickness correlations, and showed a positive association between conduct disorder symptom count and cortical thickness in a superior temporal gyrus cluster.Functional group differences may reflect a more nuanced cortical morphometric difference than ROI cortical thickness. Further investigation of morphometric differences is needed. If replicable findings can be established, they may aid in developing improved diagnostic or more targeted treatment approaches.

Aims:Alcohol, druguse, andweaponcarryingare apublichealth concern especially among students because they can have deleterious effects on physical and mental health. This study determined the prevalence of and gender specific factors associated with these behaviors among Thai adolescent students. Methods: A cross-sectional study in high school and vocational school in Bangkok, Thailand was conducted in 2014. Self-administrated questionnaires assessed past 30 day behaviors among students between 11 and 18 years of age (2561 students from 26 schools). Results:Overall, one fourth (24.4%) of students reported past 30 day alcohol use, 2.5% reported drug use, and 7.8% reported weapon carrying. Older youth were more likely to report drinking than those younger (p< .0001). Multivariate logistic regression analyses showed that alcohol use was almost four times higher among drug users than nondrug users (OR 3.93). Students who carried a weapon had nearly three times the risk of drinking than their counterparts (OR 2.74). Overall, females who used drugs or who carried a weapon were 7.94 and 3.15 times respectively to report drinking compared to males. All other factors adjusted for were also more strongly associated with drinking among females than males; factors include number of friends who smoke (OR 2.66 vs OR 1.77), weight issues (OR 2.10), smoking (OR 5.36 vs OR 4.59), and energy drink use (OR 3.41 vs OR 2.04). Conclusions: An increased association of drug use and weapon carrying with alcohol use was found for adolescent females in Thailand. Findings indicate gender specific interventions are needed for adolescents for these behaviors. Financial support: Financial support from the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0184/2553) to On-anong Saiphoklang and Professor Kua Woongboonsin, PhD is acknowledged. And University of Florida Substance Abuse Training Center in Public Health (DA-T32035167).

Aims: Abused drugs activate dopaminergic (DA) “reward” regions (dorsal and ventral striatum, midbrain), promoting further drug-taking. While adverse effects lead most adolescents to limit risky drug use, some with genetic vulnerabilities to substance use disorders (SUD) and conduct problems, undeterred by risks, press on, developing SUD. We asked: (1) is the enhanced vulnerability of those youths mediated by excess reward-system activity, or by deficient inhibition of risky behaviors; (2) do those mechanisms differ by gender? Methods: Our fMRI analyses of 41 adolescent patients with severe SUD and conduct problems (20 males) and 40 comparison youths (20 males) continue. In each of 90 risky-decision trials youths decided between pressing a cautious button to earn 1 cent, or a risky one that either won 5 or lost 10 cents. Riskypress “win” odds gradually fell from 0.78 to 0.22. We analyzed brain activity during 4-sec pre-response deliberations with voxel-level and cluster-level FWE correction before risky, and separately before cautious, presses. Results: Making cautious responses required inhibiting the more-rewarded risky ones; to do so, bothmale and female comparison youths significantly activated frontopolar, temporal, parietal, or cerebellar regions, or DLPFC, more than patients; the regions differed by gender. No group activated DA regions before cautious responses. Before risky responses all four groups showed reward anticipation, activating DA regions. Comparison boys activatedmanymore, andcomparisongirlsmany fewer,DAvoxels than patients, but those differences were not statistically significant. Conclusions: Patients’ DA regions did not differ significantly from comparison youths’ at the power available here. Before cautious responses comparison youths more than patients activated other regions that may sustain cautious decisions despite temptations (e.g., drug availability, peer pressure). Those control-related regions may underlie patients’ and healthy youths’ differing vulnerabilities to SUD. Financial support: NIDA DA 011015; Kane Family Foundation.