Brooke Molina - US grants

DESCRIPTION (provided by applicant): This is a prospective longitudinal study of the association between Attention-Deficit/Hyperactivity Disorder (ADHD) and alcohol abuse. In this study, children with ADHD (n = 350+) were ascertained in their elementary school-aged years following their participation in the ADHD Summer Treatment Program at Western Psychiatric Institute and Clinic, University of Pittsburgh. This is by far the largest sample of its kind to examine the ADHD-alcoholism association. The non-ADHD group (n = 240 demographically similar subjects) was recruited during the first follow-up of the probands, when probands and controls ranged in age from 11 to 25 years old. In this cohort-sequential design, subjects are assessed annually through the developmental periods in which alcohol consumption is initiated, reaches its peak, and subsequently decreases in the general population. In the first five years of support, the sample was ascertained, the battery developed, and participants completed two waves of assessments. The third wave is currently underway. Preliminary findings from Wave 1 document that (1) ADHD is a risk factor for early starting, heavy consumption of, and problems with alcohol, (controlling for childhood conduct problems); (2) ADHD-control differences in alcohol problems are influenced by expectancies and the peer network; (3) family history of alcohol problems is greater in probands; and (4) treatment with stimulant medication is related to greater alcohol and other substance use. We propose to continue these annual assessments as the sample matures through young adulthood to extend our cross-sectional findings to the longitudinal, allowing testing of hypotheses regarding individual differences in the course, causes, and consequences of alcohol consumption within the ADHD sample and between the ADHD and non-ADHD samples (i.e., what differences between the groups explain alcohol vulnerability in the ADHD group). Unique features of the study include (1) the wealth of standardized and objective childhood data that characterize the proband sample in childhood, (2) complete information regarding lifetime stimulant treatment and school functioning, (3) a large sample size that will allow previously underpowered examinations of comorbidity; (4) assessment of nonalcoholic substances, and (5) comprehensive assessment of domains uniquely relevant to the development of alcoholism (e.g., alcohol expectancies, motives, peer substance use and attitudes, parental drinking, and family history of alcoholism).

This MERIT extension application requests funding for Years 16-20 to continue study ofthe onset, course, causes, and consequences of alcohol use and alcohol use disorders in the Pittsburgh ADHD Longitudinal Study (PALS). In the PALS, 364 children with ADHD (probands) were ascertained in their elementary school-aged years following their participation in the ADHD Summer Treatment Program atWPIC, University of Pittsburgh. This is the largest study of its kind: rigorously diagnosed ADHD in childhood, comprehensive childhood data (including standardized and objective data), and detailed longitudinal assessments to adulthood of domains theoretically related to the development of alcohol outcomes (e.g., alcohol expectancies; family history of alcoholism). A nonADHD demographically similar group of participants (n=240) was recruited during grant Years 1-5 when probands were first followed up between the ages of 11 and 25. Using a cohort-sequential design, ADHD and nonADHD participants were interviewed annually with a high rate of retention to age 23 and at ages 25, 27, and 30; a multiple reporter approach has been adopted throughout. A sampling of findings includes: 1) a higher risk for heavy drinking and AUD by proband adolescents; 2) stronger prediction to late adolescent drinking for probands when parental knowledge is below sample median; 3) mediating role of academic performance, social impairment, delinquency, and ADHD symptom persistence; 4) stronger relation between adolescent and young adult drinking for ADHD vs. nonADHD; 5) potential contribution of alcohol use to ADHD-related elevated risky driving behavior and intimate partner violence in early adulthood; and 6) continued need for collateral report of behavior (specifically, ADHD symptoms) into adulthood. Continuation of interviews is proposed, for most participants through the late 20s and early 30s, to determine whether early heavy drinking patterns persist, whether new cases of AUD develop, to examine all alcohol outcomes in relation to differential achievement of adult milestones (employment, marriage, parenthood), and to study the putative causal mechanisms underlying these AUD developments and consequences in early adulthood.

The purpose of this contract is to study the long-term effects of different treatment modalities for children with attention deficit hyperactivity disorder (ADHD) through a systematic follow-up of the subjects who participated in the Multimodal Treatment Study of Children with ADHD (MTA). The initial design and planning phase of the MTA study occurred during the latter portion of 1992 thru the end of 1993, where the divergent study designs and goals of the various investigators were blended into a cohesive, coherent, and scientifically rigorous final design. The 24-month MTA Study (14 months of treatment, followed by a 10-month follow-up assessment) of 579 children with ADHD was conducted at seven treatment sites over the course of the next four years. Participants were assessed before, during, and at the end of 14 months of treatment, and 10 months later. Treatment was received depending on to which one of four groups participants were randomized (medication alone, behavioral treatment alone, medication plus behavioral treatment, community treatment as usual). This five-year period was supported by NIMH cooperative agreement grants to the clinical sites. At the 24-month point, a Local Normative Control Group of grade- and school-matched non-patients was added as a comparator group. With the support of a subsequent competing supplement to each site, 36-month follow-up assessments were completed. The original MTA aims addressed the following questions: What are the differences in effectiveness for medication management versus intensive behavioral treatments? What are the additive/synergistic effects of combined medication and psychosocial treatment compared to either treatment delivered alone? What is the relative effectiveness of systematic, well-delivered treatments vs. [unreadable]standard[unreadable] treatments typically received in the community? Additional questions the MTA investigators sought to address included the prediction and mediation of treatment-related gains from individual (e.g., co-morbidity), familial (e.g., child-rearing practices), and/or social (e.g., SES) variables. This current contract supports assessment and data collection for follow-up year 12 of the MTA study, at the seven original sites. Each site is supported by an individual contract to that site.

DESCRIPTION (provided by applicant): Disruptive behavior disorders (DBDs;conduct disorder and oppositional-defiant disorder) with severe aggression constitute a public health problem for which evidence-based treatment options are limited. Increasing numbers of youth with aggression are being treated with atypical antipsychotics without good evidence of safety or incremental advantage over safer stimulants. This double-blind, placebo-controlled, parallel groups study will compare the effectiveness of (a) parent training in behavior management (PMT) + placebo (PBO), (b) PMT + d-methylphenidate (d-MPH), and (c) PMT + d-MPH + risperidone (RIS) in children with severe aggression, primary DBDs, and comorbid ADHD. Participants must exhibit a clear history and current pattern of serious physical aggression (i.e., moderate or higher scores on the Modified Overt Aggression Scale (OAS-M), a Clinical Global Impressions (CGI) Scale Severity score of 4 or higher for aggression), and high scores on the on the Disruptive-Total of the Nisonger Child Behavior Rating Form (NCBRF) . The primary aims are to determine (a) if PMT + d-MPH are superior to PMT+ PBO and (b) if PMT + d-MPH + RIS are superior to PMT + d-MPH and to PMT + PBO. Secondary aims include determining whether type of aggression (reactive vs. proactive) moderates treatment response. Design: Two hundred sixteen children across 4 sites (Case Western Reserve, Ohio State, Pittsburgh, &Stony Brook) will be randomized to 9 weeks double-blind of PMT + PBO (n=72), PMT + MPH (n=72), or PMT + MPH + RIS (n=72). All groups will receive a 12-session course of carefully monitored, empirically-based PMT. Responders will be followed on their assigned treatments in a 12-week Extension, and all participants will be assessed at one year after baseline. Clinical change will be measured by (a) parent ratings on the NCBRF &ADHD Symptom Checklist (CL);(b) teacher ratings on the ADHD Symptom CL;(c) clinician interview of the child with OAS-M;(d) clinician CGI-Improvement score (CGI-I);and direct observations of child-parent behavior. The primary outcome measure is the NCBRF Disruptive Total score;secondary outcomes are CGI-I, response rate (NCBRF reduction of at least 25%, plus CGI-I score of 1 or 2), other NCBRF and ADHD Symptom Checklist subscales, and cognitive tests. Baseline score on the Antisocial Behavior Scale will assess type of aggression (reactive or proactive) as a potential moderator. AEs and tolerability will also be assessed. This study will assess the use of placebo, d-methylphenidate (Focalin), and d-methylphenidate plus risperidone (an atypical antipsychotic drug;brand name Risperdal) against the back-drop of behavior therapy which will be taught to the parents of participants. The participants will be children ages 6 to 12 years, inclusive, who have been diagnosed with a disruptive behavior disorder plus ADHD and who display significant aggressive behavior. Given the increasing rates and severity of violence in our society, this investigation will help to determine if drug therapy, combined with parent-provided behavior therapy, can reduce child aggression.

The purpose of this contract is to study the long-term effects of different treatment modalities for children with attention deficit hyperactivity disorder (ADHD) through a systematic follow-up of the subjects who participated in the Multimodal Treatment Study of Children with ADHD (MTA). The initial design and planning phase of the MTA study occurred during the latter portion of 1992 thru the end of 1993, where the divergent study designs and goals of the various investigators were blended into a cohesive, coherent, and scientifically rigorous final design. The 24-month MTA Study (14 months of treatment, followed by a 10-month follow-up assessment) of 579 children with ADHD was conducted at seven treatment sites over the course of the next four years. Participants were assessed before, during, and at the end of 14 months of treatment, and 10 months later. Treatment was received depending on to which one of four groups participants were randomized (medication alone, behavioral treatment alone, medication plus behavioral treatment, community treatment as usual). This five-year period was supported by NIMH cooperative agreement grants to the clinical sites. At the 24-month point, a Local Normative Control Group of grade- and school-matched non-patients was added as a comparator group. With the support of a subsequent competing supplement to each site, 36-month follow-up assessments were completed. The original MTA aims addressed the following questions: What are the differences in effectiveness for medication management versus intensive behavioral treatments? What are the additive/synergistic effects of combined medication and psychosocial treatment compared to either treatment delivered alone? What is the relative effectiveness of systematic, well-delivered treatments vs. [unreadable]standard[unreadable] treatments typically received in the community? Additional questions the MTA investigators sought to address included the prediction and mediation of treatment-related gains from individual (e.g., co-morbidity), familial (e.g., child-rearing practices), and/or social (e.g., SES) variables. This current contract supports assessment and data collection for follow-up year 12 of the MTA study, at the seven original sites. Each site is supported by an individual contract to that site.

DESCRIPTION (provided by applicant): Despite the well-documented variable but often persisting course of Attention-Deficit/Hyperactivity Disorder (ADHD) into adulthood, little is known about underlying neural correlates of adulthood outcome. Neuroimaging studies of ADHD adults typically include small subsets of ADHD children who, as adults, self-report symptoms to clinicians. Thus, adults with limited insight into their ADHD (a well-known characteristic), or adults who fail to seek treatment (the majority with childhood ADHD), are excluded from these studies. A study of brain function in adults with well-characterized childhood ADHD, with collateral reports and repeated assessment of symp- toms from childhood into adulthood, may contribute needed information about the pathophysiology of ADHD. Existing studies of adult ADHD have typically focused on the functioning of dorsal and lateral prefrontal sys- tems underlying cool executive functions (EF). However, recent evidence suggests that fronto-striatal-limbic systems supporting processing at the interface of cognition and motivational/emotional processes - also known as hot EF and implicated in self-regulation of behavior and emotion - may also be impaired in ADHD. This application proposes to examine the functioning of neural systems supporting both cool and hot EF in relation to powerful latent variable growth curves of ADHD symptoms estimated from the uniquely frequent long-term assessments reaching beyond age 25 of the Pittsburgh ADHD Longitudinal Study (PALS). Partici- pants will be 200 young adults (150 with, and 50 without, childhood ADHD) from the PALS -- an ongoing study (R37AA11873) of the course and outcomes of childhood ADHD. Using fMRI paradigms, we will assess neural activity in, and functional connectivity between, neural regions implicated in a) reward modulation of inhibitory control during a rewarded antisaccade task and b) interference control of emotionally salient information during an emotional working memory task. Importantly, given recent evidence that emotional dysregulation (specifical- ly, anger-irritability) may have distinct neurobiological substrates in ADHD, we will test the extent to which vari- ation in the above neuroimaging indices is associated with anger-irritability also measured longitudinally. Neu- roimaging indices will be tested as moderators of the relations between symptom course and performance on tasks assessing affective decision making, risk taking, and affective response inhibition. Finally, we will explore associations between these neuroimaging indices of rewarded inhibitory control and emotional working memory and a) white matter integrity, b) stimulant treatment history, and c) self-reported variables such as re- ward sensitivity and positive/negative urgency. The proposed study will be unique in the adult ADHD neuroim- aging literature due to its emphasis on the dual cool and hot EF systems in adults with well-characterized childhood histories prospectively tracked into adulthood with uniquely frequent repeated assessments tapping underlying traits over time. The integrated brain-behavior findings may stimulate research on new targets for therapeutic interventions and advance understanding of ADHD pathophysiology.

DESCRIPTION (provided by applicant): Nonmedical use of psychoactive stimulant medication (medication that is prescribed for the treatment of Attention-Deficit/Hyperactivity Disorder; ADHD) is an increasingly prevalent form of prescription drug misuse among young adults and in particular college students (Smith & Farah, 2011; Wilens et al., 2008). Prevalence rates of nonmedical use (use without a prescription) on college campuses are rising (e.g., DeSantis et al., 2008). Stimulant-related emergency department visits have increased threefold in recent years (SAMHSA, 2013a). College students with prescriptions are the primary source of stimulant diversion (giving away or selling one's medication). However, no clinical strategies for management of this problem have been developed for primary care providers - a professional population that frequently treats ADHD and that is being targeted by NIDA (Volkow, 2012), especially with regard to nonmedical use of prescription drugs including stimulants (Volkow, 2010). Our preliminary focus groups with primary care providers revealed either lack of awareness about stimulant diversion/misuse or lack of strategies for addressing it; all indicated concern. This R34 application proposes the initial development of brief clinical strategies that primary care providers may use to prevent diversion of stimulants by their patients with ADHD. We focus on family medicine and pediatric providers treating 18-25 year olds in post-secondary education. Within the context of the R34 Program Announcement PA-12-171, Pilot and Feasibility Studies in Preparation for Drug and Alcohol Abuse Prevention Trials, we will 1) survey providers and their physician-extenders (nurse practitioners and physician assistants) about their current practices; 2) develop and pilot test strategies for prevention of diversion to e utilized within the context of the provider:patient relationship; and 3) examine, using post- implementation survey and EMR data, provider, practice, and patient variables associated with feasibility, satisfaction, and implementation. We base our selection of variables to consider in strategy development and evaluation on Weiner's theory of innovation implementation (Weiner et al., 2009). We propose inclusion of key stakeholders (community providers) and relevant consultants in the development process to enhance innovation feasibility and implementation. The development of these strategies will be innovative due to their complete absence in the evidence-based ADHD treatment guidelines literature. The project addresses an immediate public health concern: escalating non-prescribed use of a Schedule II prescription medication (CNS stimulants) by college students. Addressing this knowledge gap has the ultimate potential, following an R01- funded well-powered study of effectiveness and moderators, to provide one pragmatic, low cost, and highly disseminable means by which prescription stimulant diversion may be decreased.

? DESCRIPTION (provided by applicant): Attention-Deficit/Hyperactivity Disorder (ADHD), one of the most common mental health conditions with origins in childhood, predicts early adulthood substance use disorders (SUDs). However, these outcomes are highly variable and often emanate from research that was not developmentally informed. Most importantly, research that seeks to explain this variability by focusing on mediators and moderators of SUD risk, beyond Conduct Disorder comorbidity and stimulant treatment, needs expansion to inform treatment and prevention. The prospective longitudinal follow-up of the children in the MTA (Multimodal Treatment of ADHD), a multi-site study that began as a randomized clinical trial of medication management, behavior therapy, and their combination for childhood ADHD Combined Subtype, provides a unique opportunity to address these concerns. The MTA sample is large (579 ADHD; 289 classmate comparison children), with good retention over 16 years into early adulthood, and it provides ample power for new and innovative tests of theory-driven hypotheses about mediators and moderators of ADHD-related risk of SUD. The narrow age range at recruitment (7-9.9) combined with longitudinal tracking improves power to test age-specific associations and developmental unfolding of contributing variables with implications for timing of interventions. The multi-site design and recruitment strategies improve generalizability of findings. Prospective data from childhood (pre- substance use) to early adulthood include comprehensive substance use measures and multiple-reporter assessments of variables pertinent to SUD risk. Data collection for the 16-year follow-up of the MTA sample, when participants were in their mid-20s, was completed in 2013 with NIDA contractual support. Funds were provided for data collection but limited support was provided for data analysis-and this support ended before adult data were available. Thus, this application seeks funding crucial to support the collaborative analytic work needed to test mechanistic developmental hypotheses, beyond simple bivariate associations tested to date, about ADHD-related onset, escalation, course, and causes of substance use and SUD into early adulthood in the MTA. We emphasize tests of theory-informed hypotheses from our recent published review that integrated literature on the etiology of drug abuse risk in typical and high risk children with the recent literature on ADHD- related impairments in adolescence and adulthood. Innovative tests of these hypotheses will have implications for understanding developmental specificity of risk processes, particularly in the transition to adulthood. Insights from the findings may identify novel treatment targets for this developmental bridge into adulthood.

? DESCRIPTION (provided by applicant): Nonmedical use of psychoactive stimulant medication (medication that is prescribed for the treatment of Attention-Deficit/Hyperactivity Disorder; ADHD) is an increasingly prevalent form of prescription drug misuse among high school students (McCabe & West, 2013) and prevalence rates continue to rise. Stimulant-related emergency department visits increased threefold in recent years (SAMHSA, 2013a). Students with prescriptions are the primary source of stimulant diversion (selling, sharing one's medication). However, with the exception of developmental research we recently launched, clinical strategies for management of stimulant diversion have yet to be developed and empirically evaluated for primary care providers - a professional population that frequently treats ADHD and that is being targeted by NIDA (Volkow, 2012), especially with regard to nonmedical use of prescription drugs including stimulants (Volkow, 2010). Our work with primary care providers revealed 1) concern about the problem, 2) a lack of strategies for addressing it, and 3) willingness to adopt new strategies to decrease diversion potential. This application proposes to test the implementation of brief clinical practice strategies, designed to prevent stimulant diversion that pediatricians may use with their teenage patients receiving stimulant prescriptions and their parents. In response to RFA-DA-15-010, Interventions for youth who misuse/abuse prescription stimulant medications in high school and/or college-attending youth (U01), we will conduct a randomized trial to examine the effect on patient diversion, attitudes, and intentions, of an intervention to be delivered by pediatric providers at the time of stimulant prescribing. N=375 13-17 year old patients will be enrolled across six pediatric practices for assessment prior to, and following, provider training in stimulant diversion practices. Following baseline assessment, providers at half of the practices, randomly selected within matched pairs, will receive training in the Stimulant Diversion Prevention (SDP) protocol; the remainder will implement Treatment as Usual (TAU). Providers and parents will also participate in the assessments and electronic medical record data will be collected for participating patients. We will also characterize prescribing patterns in all participating and non participating practices in the UPMC pediatric provider network independent of study participation (543 pediatricians) for comparison to regional trends. The results of this study will provide the first empirical test of a brief provider-led intervention for stimulant diversion reduction in primary care. The goals are innovative given the complete absence of such strategies in evidence-based ADHD treatment guidelines. The project addresses an immediate public health concern and is based on developmental work (R34 DA035464) that includes stakeholders (providers) as consultants to develop feasible strategies with a high likelihood of delivery. Thus, the impact of the work is expected to be high, with the result being a pragmatic, low cost, and highly disseminable means by which prescription stimulant diversion may be decreased.

This is a renewal application for five years of continuing support from an established T32 (AA07453) that was first funded in 1982. This application seeks support for three postdoctoral fellows per year. The Alcohol Research Training Program at the University of Pittsburgh is a small, strong, and consistently productive T32 that has trained 41 postdoctoral fellows, 84% of whom are in academic or research positions. Further, the trainees have exceptional success obtaining research funding compared to the national average. The trainees? scholarly output addresses areas of central importance in alcohol research such as onset of alcohol use among children and ontogeny of risk factors for alcohol disorders, long-term effects of prenatal alcohol exposure, effectiveness of prevention and treatment programs for dually-diagnosed patients, and the relation between alcohol abuse and the natural history of AIDS. In response to current research needs in the field of alcohol research, we have re-titled this T32 to Developmental Alcohol Research Training (DART) to establish a new focus: addressing alcohol use and addiction from a developmental perspective focusing on gestation to young adulthood. This emphasis fits entirely with the NIAAA strategic plan to prioritize research on alcohol use disorders as developmental in nature. The DART Program is unique in the NIAAA training portfolio both in its focus on development and the large number of resources available to trainees. The faculty of the training program are highly experienced and can offer direction and mentorship in areas of high priority to NIAAA such as the developmental stages of alcohol use and abuse, timing and consequences of alcohol use, racial and gender differences, and the effects of health disparities on the development of alcohol use and misuse. The faculty have expertise in developmental, epidemiological, clinical, and neurobiological approaches, and advanced quantitative methods. A significant strength of the Program is access to an unusually large number of NIH-funded research projects that include large, longitudinal cohorts and allow analyses across multiple developmental points. The identification of supporting faculty who are not specifically alcohol researchers, but who have parallel expertise in fields such as emergency medicine, nutrition, pediatrics, and statistics, allows trainees to develop their research using novel combinations of methods and expertise. Training involves active participation on research projects with mentors, supplemented by courses in Addictive Behaviors, Developmental Psychopathology, Epidemiology, and Biostatistics, and by the required Integrated Addictions Research Seminar and the Career and Research Development Seminar. The DART program faculty are committed to training researchers to become independent investigators with the skills and tools for collaborative, multidisciplinary research in developmental studies of alcohol use and abuse in order to accomplish excellence and innovation in developmental alcoholism research.

Project Summary Alcohol misuse (e.g., binge drinking) in mid-adulthood and its negative consequences, including alcohol use disorder (AUD) are prevalent, increasing, and expensive. In the last decade, high risk drinking increased 37% and AUD 47% among 30-44 year olds (and even more at older ages). Excessive drinking cost the U.S. $249 billion and is among the leading preventable causes of death in this country. Psychiatric comorbidity is the rule rather than the exception among problem drinkers, particularly after age 30. Given the trajectory of this societal burden, NIAAA has prioritized a developmental approach to the identification of mechanisms underlying alcohol misuse and problems and co-occurring mental health conditions across the lifespan (Goals 1-2, Objective 1a). The Pittsburgh ADHD Longitudinal Study (PALS) was designed to prospectively study the onset, course, and causes of AUD in a large cohort of children at risk for alcohol problems---those diagnosed with one of the most prevalent childhood psychiatric disorders, Attention-Deficit/Hyperactivity Disorder (ADHD). ADHD predicts early onset (adolescent) alcohol use, increased alcohol-related problems, and AUD in emerging adulthood but mechanisms of alcohol problem risk into mid-adulthood are unknown. Moreover, ADHD complicates AUD treatment (e.g., relapse rates are much higher). Research on adult ADHD has exploded, but amply powered longitudinal studies of childhood ADHD into mid-adulthood, when drinking problems become entrenched and mediating variables have recently been shown to change, are absent from the literature and are now even more crucial given the proliferation, and limitations, of cross-sectional studies of adult ADHD and AUD. Moreover, data are needed on the dynamic nature of within-person, daily risk processes not captured in traditional infrequent assessments (e.g., daily fluctuations in, and effects of, impulsivity and mood on alcohol use as a function of context) that may be unique and incrementally informative for individuals with ADHD. The PALS is a well-characterized, well-retained (>90% retention) sample (365 ADHD, 227 nonADHD) prospectively studied from childhood to age 29 with ongoing age-targeted assessments; age 35 assessments are partially collected. We propose a novel continuation of our cohort-sequential design to age 39 that includes an embedded 17-day ecological momentary assessment (EMA) at age 37 to assess short- and long-term within-person developmental pathways from childhood ADHD to mid-adulthood alcohol problems. The PALS has the capacity to test pathways to alcohol problems (including negative affect-related) that are more likely to emerge in older adulthood. Findings have the potential to identify novel and malleable contributors to mid-adulthood AUD and inform intervention opportunities for a prevalent, intractable comorbidity.

Project Summary Diversion of ADHD stimulants, by sharing, selling, or trading, is the primary conduit by which these Schedule II controlled drugs reach their peak prevalence of misuse in early adulthood (use without a prescription, overuse of prescribed medication). Yet, understanding of stimulant diversion and contributing factors is limited to speculation from small cross-sectional studies. Dramatically increased rates of stimulant prescribing in recent years (from ~49.2 to 62.8M people), mainly in adults, has heightened concern. The state- of-science on this important topic precludes development of prevention efforts based on variables with inferred causal influence. Additionally, although primary care is the most common treatment setting for ADHD, this population and its risk for diversion in adulthood, including when diagnosis and treatment occurs after childhood, is poorly understood. Due to concern about these trends and reports of associated physical dangers and legal consequences, the FDA recently established a public docket requesting comments on the potential role of abuse- deterrent stimulant formulations. The accompanying review stated a need for information on factors that would inform their decision-making, including characterization of longitudinal pathways to misuse. The proposed study prospectively examines stimulant diversion and hypothesized risk factors among young adults at peak age for stimulant diversion: those initially diagnosed and stimulant-treated in early adulthood, and those stimulant-treated as adolescents by pediatricians and aging now into early adulthood. The combined sample will provide a unique opportunity to examine associations between timing of ADHD treatment, stimulant diversion, and hypothesized risk factors. N=357 adolescents stimulant-treated for ADHD in primary care (U01 DA040213), and 150 newly recruited young adults first diagnosed and treated in adulthood, will be studied (total n = 507). Three annual assessments will span ages 18-24 to allow prospective study of stimulant diversion during the age period of its greatest prevalence. Self- and parent-report and behavioral economics tasks will be used to assess intrapersonal, attitudinal-behavioral, and social-normative risk factors and environmental moderators (parenting and provider factors). The results of this study will aide Priority Focus Area #3 of NIDA?s 2016-2020 Strategic Plan, ?Addressing Real World Complexities? by generating findings that will apply to two of the largest, least understood segments of the treated ADHD population?those treated in primary care, and those young adult-diagnosed. Findings will provide crucially needed prospectively gathered data to inform the development of stimulant diversion prevention efforts.

There is a striking dearth of longitudinal studies of alcoholism ontogeny to mid-adulthood from earlier developmental periods. The extent to which heavy drinking in adolescence and early adulthood persists into later life, and the reasons for its progression to mid-adulthood when employment and family responsibilities are approaching the ?ascendant? midlife phase, is vastly under-studied. This is particularly problematic considering that high-risk drinking has increased 37% and AUD 47% among 30-44 year olds. NIAAA has prioritized a developmental approach to the identification of mechanisms underlying alcohol misuse and problems and co- occurring mental health conditions across the lifespan (Goals 1-2, Objective 1a). Cross-sectional research suggests shifting mechanisms of vulnerability with age, from positive to negative reinforcement processes. The Pittsburgh ADHD Longitudinal Study (PALS) is uniquely suited to address these important questions for a high-risk population: adults with a childhood diagnosis of Attention Deficit Hyperactivity Disorder (ADHD). The PALS was designed to prospectively study the onset, course, and causes of AUD in a large cohort of children with ADHD -- an established risk factor for adolescent and young adult AUD. The sample is currently aging through their 30s with > 90% retention (360 ADHD, 224 nonADHD) and provides a unique opportunity to test hypotheses about changing mechanisms of AUD risk and recovery over a large age span, into the late 30s, without empirical precedent. We propose to capitalize on the current age of the PALS sample to take advantage of this opportunity, with a novel emphasis on understanding the intersection of impulsivity and mood as it relates to ADHD risk for AUD. In addition to a wealth of prospectively assessed self- and informant-reported variables collected longitudinally in the PALS, the proposed new, expanded assessments stretching into mid-adulthood will include an ecological momentary assessment protocol (EMA) and behavioral task indices of impulsivity. The proposed 20-day EMA burst embedded in the prospective longitudinal design will characterize the dynamic nature and temporal ordering of alcohol risk processes (e.g., shift in impulsivity) not captured in traditional assessments and will integrate environmental (e.g., interpersonal stress) and individual factors (e.g., negative mood, sleep disturbances) to which individuals with ADHD may be more sensitive. Coupled with integrated examination of etiological processes across important developmental windows (adolescence, young adulthood, mid-adulthood), the prospective, expanded assessments (at ages 35, 37, and 39, with a 20-day EMA at age 35 or 37) will enhance understanding of developmental processes in relation to worsening and improving course of heavy drinking and alcohol problems through mid-adulthood when life altering consequences become especially costly. Results hold promise for developing personalized medicine treatment targets that may be particularly efficacious for reducing AUD risk among adults with a history of ADHD.