A Behavioral Test of Accepting Benefits that Cost Others: Associations with Conduct Problems and Callous-Unemotionality

Background: Youth with conduct problems (CP) often make decisions which value self-interest over the interests of others. Self-benefiting behavior despite loss to others is especially common among youth with CP and callous-unemotional traits (CU). Such behavioral tendencies are generally measured using self- or observer-report. We are unaware of attempts to measure this tendency with a behavioral paradigm. Methods/Principal Findings: In our AlAn’s (altruism-antisocial) game a computer program presents subjects with a series of offers in which they will receive money but a planned actual charity donation will be reduced; subjects decide to accept or reject each offer. We tested (1) whether adolescent patients with CP (n = 20) compared with adolescent controls (n = 19) differed on AlAn’s game outcomes, (2) whether youths with CP and CU differed significantly from controls without CP or CU, and (3) whether AlAn’s game outcomes correlated significantly with CP and separately, CU severity. Patients with CP and CU compared with controls without these problems took significantly more money for themselves and left significantly less money in the charity donation; AlAn’s game outcomes were significantly correlated with CU, but not CP. Conclusions/Significance: In the AlAn’s game adolescents with conduct problems and CU traits, compared with controls without CP/CU, are disposed to benefit themselves while costing others even in a novel situation, devoid of peer influences, where anonymity is assured, reciprocity or retribution are impossible, intoxication is absent and when the ‘‘other’ ’ to b

Brain Cortical Thickness Differences in Adolescent Females with Substance Use Disorders.

METHODS: We recruited right-handed female patients, 14-19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses. RESULTS: A priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size). CONCLUSIONS: Adolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies

Risky Decisions and Their Consequences: Neural Processing by Boys with Antisocial Substance Disorder

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.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.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

CTN Multiple Comparisons Procedures SOP

This procedure is intended for the Lead Investigator and Protocol Development Team within the Clinical Trials Network as guidance for the consideration of multiple statistical comparisons within a protocol.  The Statistics Workgroup of the Data Management and Analysis Subcommittee will examine the proposed rationale for addressing multiple comparisons when reviewing protocols

Supplementary Materials to On Using Empirical Bayes Predictors

Supplementary materials (including additional examples, simulations, and code) to the paper: On Using Empirical Bayes Predictors from Generalized Linear Mixed Models to Test and Visualize Associations among Longitudinal Outcome

Longitudinal Marijuana and Alcohol Useage Data

<p>Data example consisting of marijuana joints smoked per day and daily alcohol use (yes, no) during 112 days of treatment on 65 adolescents who completed a pharmacotherapy trial for attention defecit hyperactivity disorder and substance use and who were regular users of both drugs at baseline.</p

Timeline Followback Polysubstance Use Entry-Summary-Storage System, Version 7

Timeline Followback (TLFB) has been a widely used, gold standard method for collecting daily substance use information. To satisfy the need to more efficiently and accurately capture the polysubstance use common for many users, we have developed the Timeline Followback Polysubstance Entry-Summary-Storage (TLFB Poly ESS) system a user-friendly, calendar-based system in Microsoft Excel that collects quantity and frequency of use information for multiple substances, provides clinical summary information, and stores data in a format conducive for trajectory analyses evaluating use patterns over time. Different versions have been implemented in research, clinical treatment and school-based treatment programs. The current version 7 specifically allows for tracking daily quantity of alcohol use (drinks), quantity of marijuana use (grams), any nontobacco substance use, and primary drug use. Features are: <p>·        A pull-down menu that automatically populates drug categories throughout the data collection period of interest, reducing errors in collection <br></p> <p>·        Entry of key date (i.e. program start date) to auto-populate calendar days/dates and entry of anchor events to facilitate recall<br></p> <p>·        Summary worksheet that automatically calculates days used each drug per month, total units per month and average units per day for alcohol and marijuana </p> <p>·        Macro that transfers data for storage into a common longitudinal format conducive for trajectory analyses of daily information and use patterns</p><p>Additional versions are under development and we anticipate their availability in 2017.  Questions can be addressed to [email protected]<br></p><p><br></p

Timeline Followback Polysubstance Entry-Summary-Storage Poster Presentation for 2016 APA

Poster from the 2016 American Psychological Association Meeting describing the Timeline Followback Polysubstance Entry-Summary-Storage (TLFB Poly ESS) system<br

Modeling Site Effects in the Design and Analysis of Multi-site Trials

Background: Careful consideration of site effects is important in the analysis of multi-site clinical trials for drug abuse treatment. The statistical choices for modeling these effects have implications for both trial planning and interpretation of findings. Objectives: Three broad approaches for modeling site effects are presented: omitting site from the analysis; modeling site as a fixed effect; and modeling site as a random effect. Both the direct effect of site and the interaction of site and treatment are considered. Methods: The statistical model, and consequences, for each approach are presented along with examples from existing clinical trials. Power analysis calculations provide sample size requirements for adequate statistical power for studies utilizing 6, 8, 10, 12, 14, and 16 treatment sites. Results: Results of the power analyses showed that the total sample required falls rapidly as the number of sites increases in the random effect approach. In the fixed effect approach in which the interaction of site and treatment is considered, the required number of participants per site decreases as the number of sites increases. Conclusions: Ignoring site effects is not a viable option in multi-site clinical trials. There are advantages and disadvantages to the fixed effect and random effect approaches to modeling site effects. Scientific Significance: The distinction between efficacy trials and effectiveness trials is rarely sharp. The choice between random effect and fixed effect statistical modeling can provide different benefits depending on the goals of the study

The importance of distribution-choice in modeling substance use data: a comparison of negative binomial, beta binomial, and zero-inflated distributions

<div><p></p><p><i>Background</i>: It is important to correctly understand the associations among addiction to multiple drugs and between co-occurring substance use and psychiatric disorders. Substance-specific outcomes (e.g. number of days used cannabis) have distributional characteristics which range widely depending on the substance and the sample being evaluated. <i>Objectives</i>: We recommend a four-part strategy for determining the appropriate distribution for modeling substance use data. We demonstrate this strategy by comparing the model fit and resulting inferences from applying four different distributions to model use of substances that range greatly in the prevalence and frequency of their use. <i>Methods</i>: Using Timeline Followback (TLFB) data from a previously-published study, we used negative binomial, beta-binomial and their zero-inflated counterparts to model proportion of days during treatment of cannabis, cigarettes, alcohol, and opioid use. The fit for each distribution was evaluated with statistical model selection criteria, visual plots and a comparison of the resulting inferences. <i>Results</i>: We demonstrate the feasibility and utility of modeling each substance individually and show that no single distribution provides the best fit for all substances. Inferences regarding use of each substance and associations with important clinical variables were not consistent across models and differed by substance. <i>Conclusion</i>: Thus, the distribution chosen for modeling substance use must be carefully selected and evaluated because it may impact the resulting conclusions. Furthermore, the common procedure of aggregating use across different substances may not be ideal.</p></div