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.

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.

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.

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.

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.

Brain activation during the Stroop task in adolescents with severe substance and conduct problems: A pilot study.

BACKGROUND: Although many neuroimaging studies have examined changes in brain function in adults with substance use disorders, far fewer have examined adolescents. This study investigated patterns of brain activation in adolescents with severe substance and conduct problems (SCP) compared to controls. METHODS: Functional magnetic resonance imaging (fMRI) at 1.5Tesla assessed brain activation in 12 adolescent males with SCP, ranging in age from 14 to 18, and 12 controls similar in age, gender, and neighborhood while performing the attentionally demanding Stroop task. RESULTS: Even though the adolescents with SCP performed as well as the controls, they activated a more extensive set of brain structures for incongruent (e.g., "red" in blue ink) versus congruent (e.g. "red" in red ink) trials. These regions included parahippocampal regions bilaterally, posterior regions involved in language-related processing, right-sided medial prefrontal areas, and subcortical regions including the thalamus and caudate. CONCLUSION: These preliminary results suggest that the neural mechanisms of attentional control in youth with SCP differ from youth without such problems. This difficulty may prevent SCP youth from ignoring salient but distracting information in the environment, such as drug-related information.

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.

A risk-taking "set" in a novel task among adolescents with serious conduct and substance problems.

OBJECTIVE: Adolescent patients' conduct disorder and substance use disorder symptoms are "risky behaviors" with unpredictable rewards and punishments. The authors asked whether such youths also take excessive risks in new situations without prior learning, peer pressure, or intoxication. METHOD: Subjects were 20 adolescent patients in a program treating conduct disorder and substance use disorder and 20 controls. All were substance free > or =7 days; underwent substance-related, psychological, and social assessments; and performed the Balloon Analogue Risk Task: mouse presses inflated a computerized "balloon" image, each press earning 1 cent. The 30 balloons "popped" at unpredictable sizes; earnings from popped balloons were lost. A "Collect" response saved current earnings and advanced to the next balloon. RESULTS: Mean number of inflating presses: patients, 1021 and controls, 705 (p = .001); group differences were stable from the task's beginning. Mean inflating presses before a "collect" response: patients, 38.6 and controls, 24.0 (p = .0005). Mean balloons popped: patients, 9.8 and controls, 6.3 (p = .001). Patients (versus controls) reported more aggressiveness and substance use and perceived less risk from substances. Patients' responses were significantly slower than those of controls. CONCLUSIONS: From the beginning of this novel task, conduct disorder and substance use disorder patients (compared with controls) took more risks, indicating an initial risk-taking propensity, although patients' slower responses argued against "impulsive, thoughtless" behavior.

Measuring impulsivity in adolescents with serious substance and conduct problems.

Adolescents with substance use and conduct disorders have high rates of aggression and attention deficit hyperactivity disorder (ADHD), all of which have been characterized in part by impulsivity. Developing measures that capture impulsivity behaviorally and correlate with self-reported impulsivity has been difficult. One promising behavioral measure, however, is a variant of the continuous performance test, the Immediate Memory Test/Delayed Memory Test (IMT/DMT). The authors showed significant group differences between adolescents in treatment for serious substance and conduct problems and community controls on impulsivity measures, both behavioral and self-report, as well as on aggression and problem behavior measures. Furthermore, the IMT/DMT correlated significantly with self-reported impulsivity. In summary, the IMT/DMT may be an effective behavioral measure of impulsivity in adolescents.

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.

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.

What adolescents enrolled in genomic addiction research want to know about conflicts of interest.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent perspectives on the return of individual results in genomic addiction research.

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.

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.

Default mode network activity in male adolescents with conduct and substance use disorder.

BACKGROUND: Adolescents with conduct disorder (CD) and substance use disorders (SUD) experience difficulty evaluating and regulating their behavior in anticipation of future consequences. Given the role of the brain's default mode network (DMN) in self-reflection and future thought, this study investigates whether DMN is altered in adolescents with CD and SUD, relative to controls. METHODS: Twenty adolescent males with CD and SUD and 20 male controls of similar ages underwent functional magnetic resonance imaging as they completed a risk-taking decision task. We used independent component analysis as a data-driven approach to identify the DMN spatial component in individual subjects. DMN activity was then compared between groups. RESULTS: Compared to controls, patients showed reduced activity in superior, medial and middle frontal gyrus (Brodmann area (BA) 10), retrosplenial cortex (BA 30) and lingual gyrus (BA 18), and bilateral middle temporal gryus (BA 21/22) - DMN regions thought to support self-referential evaluation, memory, foresight, and perspective taking. Furthermore, this pattern of reduced activity in patients remained robust after adjusting for the effects of depression and attention-deficit hyperactivity disorder (ADHD). Conversely, when not adjusting for effects of depression and ADHD, patients demonstrated greater DMN activity than controls solely in the cuneus (BA 19). CONCLUSIONS: Collectively, these results suggest that comorbid CD and SUD in adolescents is characterized by atypical activity in brain regions thought to play an important role in introspective processing. These functional imbalances in brain networks may provide further insight into the neural underpinnings of conduct and substance use disorders.

Risky decisions and their consequences: neural processing by boys with Antisocial Substance Disorder.

BACKGROUND: Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys. METHODOLOGY/PRINCIPAL FINDINGS: We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere. CONCLUSIONS/SIGNIFICANCE: Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders.

Substance use disorder genetic research: investigators and participants grapple with the ethical issues.

OBJECTIVE: This qualitative research examined the ethical concerns regarding the psychosocial issues, research design and implementation, and application of psychiatric genetic research on substance use disorders (SUD) from multiple perspectives. METHODS: A literature review of the bioethics literature related to psychiatric genetics and focus groups explored the ethical implications of SUD genetic research. Twenty-six National Institute on Drug Abuse funded principal investigators in the field of psychiatric genetic research, nine adolescent patients in residential SUD treatment, and 10 relatives of patients participated in focus groups (held separately). The focus groups were recorded, transcribed, and the content was analyzed. The themes that emerged from the literature and the focus group transcripts were organized by using NVIVO7, a software package designed to manage, analyze, and compare narrative data. RESULTS: Investigators and the literature expressed similar concerns regarding the ethical concerns associated with psychiatric genetic research including violation of privacy, misunderstanding about psychiatric genetics, stigmatization, commercialization, discrimination, eugenics, consequences of research on illegal behavior, unforeseen consequences, altered notion of individual responsibility, and others. Patients and their relatives showed little familiarity with the ethical issues as identified by professionals and little concern regarding most of the potential risks. The exception was apprehension associated with potential criminal justice uses of stored genetic information, in particular enforced therapy and stigmatization, which elicited some concern from all perspectives. CONCLUSION: The challenge for further research is to identify risks and benefits of SUD research that are germane in a behaviorally disinhibited population and devise effective tools to communicate information to participants through an improved informed consent process.