Emotional Invalidation and Relationship Quality: A Mediational Model Through a Social Learning Lens.

While we know childhood experiences are influential on a child's later socioemotional awareness and behavior, we are still searching for specific mechanisms that influence the transferability of childhood experiences and adult relationship functioning. In this study, we seek to further this area of investigation by examining the interpretation of ambiguous social interactions and perceptions of emotional invalidation as potential mediators of the relationship between perceptions of childhood emotional invalidation and current relationship quality. Participants completed online measures of hostile intent attributions, perceptions of childhood emotional invalidation, and current relationship quality with a significant other. They read emotionally provocative interpersonal scenarios and then reported likely emotionally invalidating reactions from their significant other to measure current perceptions of emotional invalidation. Results supported our hypotheses that perceptions of current emotional invalidation in a close, personal relationship would mediate the relationship between perceptions of childhood maternal emotional invalidation and both current relationship support and relationship conflict. Furthermore, the strength of this mediational pathway outweighed the influence of a more general hostile attribution bias. These findings have implications for prevention and intervention strategies designed to enhance interpersonal functioning.

A revised prosocial behavior game: Testing associations with psychopathic traits and the effects of moral elevation using a randomized clinical trial.

BACKGROUND: Prosocial behavior is negatively associated with psychopathic traits and paradigms which measure prosocial behavior in the laboratory may be useful in better understanding moderators of this association. METHODS: We revised a previously validated game of prosocial behavior by including a new trial type (i.e., trials where the participant will lose money and the charity will gain money). This version of the game was administered online and participants were randomized to group (exposed to a control stimulus video or a video used to elicit moral elevation, i.e. a positive response to witnessing another's act of kindness). We used repeated game administration to test whether a moral elevation stimulus affected game behavior and moderated the negative association between psychopathic traits and prosocial behavior. RESULTS: Prosocial behavior on the new trial types added in this revised game correlated strongly with prosocial behavior on the old trial type (i.e., trials where the participant will gain money and the charity will lose money; r = 0.71; p-value<0.001; n = 485). Graphing trial acceptance rates by trial characteristics demonstrated expected patterns of behavior. Number of prosocial choices on the game correlated with psychopathic trait score (Levenson Factor 1 score; r = -0.52; p-value<0.001). Game repetition with a control stimulus in between runs, supported high immediate test-retest reliability of overall game behavior. Exposure to the moral elevation stimulus in between runs did not affect game behavior nor moderate the association between psychopathic traits and prosocial behavior. CONCLUSIONS: Choices on this revised game of prosocial behavior, which can be administered online, are associated with psychopathic traits scores. The game appears to have high immediate test-retest reliability. Exposure to the moral elevation stimulus did not affect prosocial behavior or impact the relationship between psychopathic trait scores and prosocial behavior. Future research should continue to test potential moderators of this relationship. Limitations of the current study are discussed.

An Approach to Biomarker Discovery of Cannabis Use Utilizing Proteomic, Metabolomic, and Lipidomic Analyses.

Introduction: Relatively little is known about the molecular pathways influenced by cannabis use in humans. We used a multi-omics approach to examine protein, metabolomic, and lipid markers in plasma differentiating between cannabis users and nonusers to understand markers associated with cannabis use. Methods: Eight discordant twin pairs and four concordant twin pairs for cannabis use completed a blood draw, urine and plasma toxicology testing, and provided information about their past 30-day cannabis use and other substance use patterns. The 24 twins were all non-Hispanic whites. Sixty-six percent were female. Median age was 30 years. Fifteen participants reported that they had used cannabis in the last 30 days, including eight participants that used every day or almost every day (29-30 of 30 days). Of these 15 participants, plasma 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) and total tetrahydrocannabinol (THC) concentrations were detectable in 12 participants. Among the eight "heavy users" the amount of total THC (sum of THC and its metabolites) and plasma THC-COOH concentrations varied widely, with ranges of 13.1-1713 ng/mL and 2.7-284 ng/mL, respectively. A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay measured plasma THC-COOH, THC, and other cannabinoids and metabolites. Plasma THC-COOH was used as the primary measure. Expression levels of 1305 proteins were measured using SOMAScan assay, and 34 lipid mediators and 314 metabolites were measured with LC-MS/MS. Analyses examined associations between markers and THC-COOH levels with and without taking genetic relatedness into account. Results: Thirteen proteins, three metabolites, and two lipids were identified as associated with THC-COOH levels. Myc proto-oncogene was identified as associated with THC-COOH levels in both molecular insight and potential marker analyses. Five pathways (interleukin-6 production, T lymphocyte regulation, apoptosis, kinase signaling pathways, and nuclear factor kappa-light-chain-enhancer of activated B cells) were linked with molecules identified in these analyses. Conclusions: THC-COOH levels are associated with immune system-related pathways. This study presents a feasible approach to identify additional molecular markers associated with THC-COOH levels.

Management of Pediatric Post-Concussion Headaches: National Survey of Abortive Therapies Used in the Emergency Department.

Children frequently present to an Emergency Department (ED) after concussion, and headache is the most commonly associated symptom. Recent guidelines emphasize the importance of analgesia for post-concussion headache (PCH), yet evidence to inform treatment is lacking. We sought to characterize abortive therapies used to manage refractory PCH in the pediatric ED and factors associated with treatment. A scenario-based survey was distributed to ED physicians at all 15 Canadian tertiary pediatric centers. Participants were asked questions regarding ED treatment of acute (48 h) and persistent (1 month) PCH refractory to appropriate doses of acetaminophen/ibuprofen. Logistic regression was used to assess factors associated with treatment. Response rate was 63% (137/219). Nearly all physicians (128/137, 93%) endorsed treatment in the ED for acute PCH of severe intensity, with most selecting intravenous treatments (116/137, 84.7%). Treatments were similar for acute and persistent PCH. The most common treatments were metoclopramide (72%), physiologic saline (47%), and nonsteroidal anti-inflammatory agents (NSAIDS; 35%). Second-line ED treatments were more variable. For acute PCH of moderate intensity, overall treatment was lower (102/137, 74%; p < 0.0001), and NSAIDS (48%) were most frequently selected. In multi-variable regression analyses, no physician- or ED-level factor was associated with receiving treatment, or treatment using metoclopramide specifically. Treatment for refractory PCH in the pediatric ED is highly variable. Importantly, patients with severe PCH are most likely to receive intravenous therapies, often with metoclopramide, despite a paucity of evidence supporting these choices. Further research is urgently needed to establish the comparative effectiveness of pharmacotherapeutic treatments for children with refractory PCH.

Sport specialization of female figure skaters: cumulative effects on low back injuries.

Objective: 1) to determine the proportion of sport specialization among female figure skaters, 2) to compare proportion of low back injuries between specialized female figure skaters and non-specialized female figure skaters, and 3) to identify an independent risk factor(s) for low back injuries in female figure skaters.Methods: A cross-sectional questionnaire study was used. Young female figure skaters were asked questions related to sport specialization and any history of low back injuries. The primary outcome variables were status of sport specialization, weekly training hours, and low back injury. Descriptive statistics, t-test, chi-square analyses, and binary logistic regressions were used.Results: Responses from 132 female figure skaters (mean age: 16.3 ± 2.7 years, age range: 8-22 years) were analyzed. Sixty-two percent (82/132) of figure skaters were specialized. Specialized female figure skaters spent more time in training (11.3 ± 6.5 hours/week) than non-specialized skaters (7.6 ± 4.9 hours/week, p = 0.001). No statistical differences were found in proportion of low back injury history between specialized (25.6%) and non-specialized female figure skaters (24.0%, p = 0.836). Chronological age was also identified as an independent risk factor for low back injuries in female figure skaters (aOR: 1.24, 95%CI: 1.00, 1.54, p = 0.048).Conclusions: The majority of female figure skaters in this cohort were specialized. An association between chronological age and low back injuries, found in the current study, may be a result of cumulative effects of participating in figure skating over time.

Postdischarge Pain Management After Thoracic Surgery: A Patient-Centered Approach.

BACKGROUND: Postoperative analgesia is paramount to recovery after thoracic surgery, and opioids play an invaluable role in this process. However, current 1-size-fits-all prescribing practices produce large quantities of unused opioids, thereby increasing the risk of nonmedical use and overdose. This study hypothesized that patient and perioperative characteristics, including 24-hour before-discharge opioid intake, could inform more appropriate postdischarge prescriptions after thoracic surgery. METHODS: This prospective observational cohort study was conducted in 200 adult thoracic surgical patients. The cohort was divided into 3 groups on the basis of 24-hour before-discharge opioid intake in morphine milligram equivalents (MME): (1) no (0 MME), (2) low (>0 to ≤22.5 MME), or (3) high (>22.5 MME) before-discharge opioid intake. Logistic regression was used to analyze the association of patient and perioperative characteristics with self-reported after-discharge opioid use. RESULTS: Univariate analysis showed that preoperative opioid use, 24-hour before-discharge acetaminophen and gabapentinoid intake, and 24-hour before-discharge opioid intake were associated with higher after-discharge opioid use. Multivariable modeling demonstrated that 24-hour before-discharge opioid intake was most significantly associated with after-discharge opioid use. For example, compared with patients who took high amounts of opioids before discharge, patients who took no opioids before discharge were 99% less likely to take a high amount of opioids after discharge compared with taking none (odds ratio, 0.011; 95% confidence interval, 0.003 to 0.047; P < .001). CONCLUSIONS: Assessment of 24-hour before-discharge opioid intake may inform patient requirements after discharge. Opioid prescriptions after thoracic surgery can thereby be targeted on the basis of anticipated needs.

Predicting Opioid Use Following Discharge After Cesarean Delivery.

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 <.001). Only a minority of patients (11.4% to 15.8%) stored leftover opioids in a locked location, and just 31 patients disposed of leftover opioids. CONCLUSIONS: Knowledge of predischarge opioid use can be useful as a tool to inform individualized opioid prescriptions, help optimize nonopioid analgesia, and reduce opioid use. Additional studies are needed to evaluate the impact of implementing such measures on prescribing practices, pain, and functional outcomes.

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.

Sideline Coverage of Figure Skating Events.

The sport of figure skating has evolved to include various disciplines and athletes continue to push the limits of the skills they perform, thus increasing the potential for injury in practice, as well as in competition. To provide optimal rink side coverage, health care professionals must be aware of the elements skaters perform and the injuries to be expected. Appropriate planning and coordination of medical services is required to ensure adequate and timely care of injured figure skaters. Protocols developed for local, national, and international events are available to assist in this process.

Low Usage of Analgesics for Pediatric Concussion-Related Pain in US Emergency Departments Between 2007 and 2015.

OBJECTIVE: To estimate the proportion of pediatric patients with a concussion who received analgesia when presenting with pain to US emergency departments, and to describe the analgesics used. STUDY DESIGN: This was a repeated cross-sectional analysis study using the National Hospital Ambulatory Medical Care Survey database of nationally representative emergency department visits from 2007 to 2015. We included children under 18 years old with isolated concussions. Survey weighting procedures were applied to generate population-level estimates and to perform multivariable logistic regression to identify factors associated with analgesic administration. RESULTS: There were an estimated 1.54 million isolated concussion visits during the 9-year study period. Pain at presentation was reported frequently (78%), with the majority rated as moderate (36%) or severe (27%). Among all children reporting pain, 42% received no analgesics, including 40% with moderate-to-severe pain intensity. Multivariable analysis found younger age, male sex, and treatment in a nonacademic hospital were all negatively associated with analgesic administration. The medications most frequently administered were acetaminophen (54%), nonsteroidal anti-inflammatories (44%), and opioids (13%). CONCLUSIONS: Analgesic medications seem to be underused in the treatment of pediatric concussion-related pain. Following acetaminophen and nonsteroidal anti-inflammatories, opioids, which are not recommended for this condition, were the most frequently prescribed analgesics. Further research should establish optimal, consistent, and responsible pain management strategies for pediatric concussions.

Testing helping behavior and its relationship to antisocial personality and psychopathic traits.

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 ($3.28vs. $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.

Nerve blocks in paediatric and adolescent headache disorders.

PURPOSE OF REVIEW: Headaches in children and adolescents are common, causing debilitating symptoms in many. Treatment of headache disorders can be complex and standard lifestyle changes as well as oral medications may offer inadequate relief. The purpose of this article is to review the mechanism of action, efficacy and technique of peripheral nerve blocks (PNBs) and the role they play in treating paediatric headache disorders. RECENT FINDINGS: Evidence for the use of PNBs in youth is limited. However, available studies show evidence of benefit in both primary and secondary headache disorders. Variability exists in the type of block, medication choice, volume infused and frequency of this treatment. There are no serious side effects associated with PNBs. SUMMARY: PNBs are well tolerated and effective as adjunctive therapy for many disabling paediatric headache disorders. The technique can be easily learned by frontline and specialty practitioners. Prospective placebo-controlled studies are needed to determine how to best maximize PNBs for headache management (i.e. medication choice, timing and so on).

The Association of Patient Satisfaction-Based Incentives with Primary Care Physician Opioid Prescribing.

PURPOSE: The opioid epidemic in the United States is an ongoing public health concern. Health care institutions use standardized patient satisfaction surveys to assess the patient experience and some offer incentives to their providers based on the results. We hypothesized that providers who report being incentivized based on patient satisfaction surveys are more likely to report an impact of such surveys on their opioid prescribing practices. METHODS: We developed a 23-item survey instrument to assess the self-perceived impact of patient satisfaction surveys on opioid prescribing practices in primary care and the potential impact of institutional incentives. The survey was emailed to all 1404 members of the Colorado Academy of Family Physicians. RESULTS: The response rate to the online survey was 10.4% (n = 146). Clinical indications for which responders prescribe opioids included acute pain (93%), cancer pain (85%), and chronic nonmalignant pain (72%). Among physicians using patient satisfaction surveys, incentivized physicians reported at least a slight impact on opioid prescribing 3 times more often than physicians who were not incentivized (36% vs 12%, P = .004). CONCLUSIONS: Efforts to improve patient satisfaction may have potentially untoward effects on providers' opioid prescribing behaviors. Our results suggest a need to further study the impact of provider incentive plans that are based on patient satisfaction scores.

Cannabis use disorder and male sex predict medical cannabis card status in a sample of high risk adolescents.

OBJECTIVE: To examine if a substance use disorder (SUD), especially cannabis use disorder in adolescence, predicts future medical cannabis card status among high-risk youth. METHODS: Data collection occurred in Denver and San Diego. We recruited adolescents, with or at high risk for SUD and conduct problems (hereafter probands) and their siblings (n=654). Baseline (Wave 1) assessments took place between 1999 and 2008, and follow-up (Wave 2) took place between 2010 and 2013. In initial bivariate analyses, we examined whether baseline DSM-IV cannabis abuse/dependence (along with other potential predictors) was associated with possessing a medical cannabis card in young adulthood (Wave 2). Significant predictors were then included in a multiple binomial regression. Self-reported general physical health was also evaluated at both time points. Finally, within Wave 2, we tested whether card status was associated with concurrent substance dependence. RESULTS: About 16% of the sample self-reported having a medical cannabis card at follow-up. Though bivariate analyses demonstrated that multiple predictors were significantly associated with Wave 2 card status, in our multiple binomial regression only cannabis abuse/dependence and male sex remained significant. At Wave 2, those with a medical cannabis card were significantly more likely to endorse criteria for concurrent cannabis dependence. There was no significant difference in self-reported general physical health. CONCLUSIONS: Cannabis abuse/dependence and male sex positively predicted future medical cannabis card holder status among a sample of high risk adolescents. Physicians conducting evaluations for medical cannabis cards should carefully evaluate and consider past and concurrent cannabis addiction.

Children's brain activation during risky decision-making: A contributor to substance problems?

OBJECTIVE: Among young children excessive externalizing behaviors often predict adolescent conduct and substance use disorders. Adolescents with those disorders show aberrant brain function when choosing between risky or cautious options. We therefore asked whether similarly aberrant brain function during risky decision-making accompanies excessive externalizing behaviors among children, hypothesizing an association between externalizing severity and regional intensity of brain activation during risky decision-making. METHOD: Fifty-eight (58) 9-11 year-old children (both sexes), half community-recruited, half with substance-treated relatives, had parent-rated Child Behavior Checklist Externalizing scores. During fMRI, children repeatedly chose between doing a cautious behavior earning 1 point or a risky behavior that won 5 or lost 10 points. Conservative permutation-based whole-brain regression analyses sought brain regions where, during decision-making, activation significantly associated with externalizing score, with sex, and with their interaction. RESULTS: Before risky responses higher externalizing scores were significantly, negatively associated with neural activation (t's: 2.91-4.76) in regions including medial prefrontal cortex (monitors environmental reward-punishment schedules), insula (monitors internal motivating states, e.g., hunger, anxiety), dopaminergic striatal and midbrain structures (anticipate and mediate reward), and cerebellum (where injuries actually induce externalizing behaviors). Before cautious responses there were no significant externalizing:activation associations (except in post hoc exploratory analyses), no significant sex differences in activation, and no significant sex-by-externalizing interactions. CONCLUSIONS: Among children displaying more externalizing behaviors extensive decision-critical brain regions were hypoactive before risky behaviors. Such neural hypoactivity may contribute to the excessive real-life risky decisions that often produce externalizing behaviors. Substance exposure, minimal here, was a very unlikely cause.

Imaging decision about whether to benefit self by harming others: Adolescents with conduct and substance problems, with or without callous-unemotionality, or developing typically.

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.

A Behavioral Measure of Costly Helping: Replicating and Extending the Association with Callous Unemotional Traits in Male Adolescents.

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.

Adolescents with substance use disorder and assent/consent: Empirical data on understanding biobank risks in genomic research.

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.

Adolescents' Neural Processing of Risky Decisions: Effects of Sex and Behavioral Disinhibition.

BACKGROUND: Accidental 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). HYPOTHESIS: Neural 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 FINDINGS: 81 adolescents (PATIENTS with substance and conduct problems, and comparison youths (Comparisons)), assessed in a 2 x 2 design ( PATIENTS: Comparisons 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/SIGNIFICANCE: Neural 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.

Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume.

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<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold. RESULTS: Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls. CONCLUSIONS: Female adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.