Sarah Pedersen, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Considerable research evidence shows that alcoholism prevalence (Breslau, et al., 2006) and alcohol use topography (Bachman, et al., 1991; Wallace, Bachman, et al., 2003) differ for African Americans compared to Caucasians. Despite these differences, relatively little research has examined what factors contribute to the alcoholism risk process in African Americans. Based on an integrative model of cross-cultural research (Smith, et al., 2006; Spillane & Smith, 2007), the goal of the proposed study is to test a model examining both potential common (disinhibited personality, response to alcohol, alcohol expectancies) and specific (social/contextual) risk factors that could account for the racial differences seen in drinking behavior. It is hypothesized that African Americans will have lower mean levels of common risk factors (e.g., disinhibition) compared to Caucasians and that contextual factors (e.g., religiosity) will differ in both mean levels and association with drinking across races. These contextual factors are thought to constrain the relation between common risk factors (e.g., disinhibition) and drinking. African American (n = 140) and Caucasian (n = 100) participants will be included in the study. One hundred and forty African American participants (mean age = 21.87, SD = 1.17; 45% male) have completed the study as part of a project examining genetic factors in African American drinking behavior (R21 AA015218, PI: Dr. Denis M. McCarthy). Caucasian participants will complete the same alcohol challenge protocol. Participants are administered a structured interview (SSAGA-II: Bucholz, et al., 1994) and complete paper and pencil questionnaires assessing drinking behavior, disinhibition, and alcohol expectancies during their first visit. On their second visit, participants consume vodka and tonic in a laboratory setting, to achieve an estimated peak BAG of 80 mg/dl (0.08%). Subjective and physiological responses to alcohol are measured every 15 minutes for the first hour and three more assessments are completed every half an hour. [unreadable] [unreadable] PUBLIC HEALTH RELEVANCE: African Americans exhibit a different drinking pattern than Caucasians, but relatively little is known about how risk and protective factors differ between these groups. Examining both risk factors that are common across racial groups and factors that may be culturally specific could provide a more complete picture of the alcohol risk process for African Americans. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The overarching aim of this Mentored Research Scientist Development Award (K01) is to provide a 5-year career development and research program that will enable the candidate to conduct innovative research on the alcoholism risk process of African Americans. African Americans are more likely to abstain from alcohol compared to European Americans. However, among those who drink alcohol, African Americans are more likely than European Americans to experience problems. The proposed project will study this discrepancy by utilizing laboratory and naturalistic assessments to examine racial differences in two widely studied risk factors for alcohol use disorders: response to alcohol and behavioral disinhibition. Research participants will be drawn from a population of young adults with maximal variability in behavioral disinhibition: adults with (and without) histories of Attention-Deficit/Hyperactivity Disorder (ADHD). The addition of naturalistic assessments will increase the ecological validity of the findings which is especially important when studying racial group differences. Participants will be recruited from ongoing longitudinal studies of children with ADHD (PI: Molina; AA11873; DA85553; MH53554). An even number of European (n = 60) and African American (n = 60) adult drinkers will be recruited and matched across race on recent drinking behavior. An even number of participants with and without ADHD histories will be recruited. Participants will complete 3 behavioral disinhibition tasks in two laboratory sessions (alcohol and non-alcohol beverage control) and questionnaires. Response to alcohol will be assessed 7 times after alcohol consumption. Participants will then complete a 10- day ecological momentary assessment period in their natural environment. T hey will respond to random prompts throughout the day to report mood, risky decision making, and environment. Participants will also initiate responding upon drinking alcohol to capture subjective response to alcohol and consequences of alcohol use. Follow-up assessments will be conducted 6 months later. The proposed project has three specific research aims: 1) Test racial differences in acute response to alcohol. 2) Test racial differences in behavioral disinhibition while sober and intoxicated. 3) Examine racial differences in the association between acute response to alcohol and intoxicated behavioral disinhibition; incorporate context-specific factors that may facilitate this association. The candidate will receive in-depth trainingin the multi-modal assessment of behavioral disinhibition, ecological momentary assessment techniques, advanced statistics, and multi-cultural training with an emphasis on the African American culture. Upon completion, the candidate will be poised to conduct high-impact research that links lab and naturalistic assessments to understand the etiology of alcohol use disorders across races. Results will inform future intervention efforts designed to decrease alcohol-related problems experienced by African Americans. PUBLIC HEALTH RELEVANCE: African American drinkers compared to European American drinkers are at increased risk for experiencing alcohol-related problems. The proposed project assesses individuals both in the laboratory and in their own natural environment to study behavioral disinhibition and acute response to alcohol as a way to understand these racial differences. Results of the project can help inform intervention and prevention efforts that will ultimately lead to a reduction in these health disparities.

DESCRIPTION (provided by applicant): Borderline personality disorder (BPD) is extremely debilitating and costly to the individual and larger community. Additionally, BPD is highly comorbid with alcohol use disorder with prevalence estimates around 50% and an even higher percentage of individuals with BPD experiencing alcohol-related problems. This comorbidity significantly worsens treatment outcomes. To date very little research has examined mechanisms that may underlie both BPD and alcohol-related problems. The proposed project examines two hallmark features of BPD, affective instability and impulsivity/disinhibition, which have also been widely studied in relation to alcohol problems to test two pathways for why individuals with BPD engage in heavier alcohol use and experience more problems while drinking. Importantly, the disinhibition and anxiolytic/stress reducing effects of alcohol have been modeled successfully in the laboratory and our current proposal utilizes cutting edge research methodology to examine this important topic. Aims: The current application tests hypotheses about differences in response to alcohol both between groups comparing individuals with and without BPD and intra-individual differences in these responses as predictors of heavy alcohol use and alcohol-related problems. Specifically, we are hypothesizing that individuals with BPD will have heightened sensitivity to the anxiolytic effects of alcohol which in turn will increase their engagement in heavy drinking behaviors as a way to regulate their affective instability. We are also hypothesizing that individuals with BPD will be more sensitive to the disinhibiting effects of alcohol compared to individuals without BPD and that this acute response will partially account for the higher number of alcohol-related problems seen in this population. Further, by examining individual differences in response to alcohol we are able to examine a continuum of these constructs which takes into account the notable heterogeneity of individuals with and without BPD. Approach: We will use a tightly controlled within-subjects laboratory alcohol administration to model change in stress response and disinhibition from sober to intoxicated. Young adult drinkers (21-30 years of age; 50% female) with and without a diagnosis of BPD will be recruited to participate (N = 100; 50 BPD and 50 non-BPD) from both the community and treatment clinics. All participants will complete Axis I and Axis II semi-structured interviews, a control and alcohol lab session, and a three-month timeline followback interview to allow us to examine how lab-based response to alcohol relates prospectively to heavy alcohol use and alcohol-related problems. In accordance with NIAAA strategic priorities on identifying mechanisms of comorbidity the proposed work takes a critical step by increasing our understanding of why BPD and alcohol-related problems are highly linked and will ultimately inform future intervention efforts designed to decrease problematic drinking behaviors for this population.

PROJECT SUMMARY Significance: Sleep disturbances are related to increased alcohol use (AU) and alcohol problems. The mechanisms that account for this association are not well understood. The proposed study will be the first to examine an integrative model including both a positive reinforcement pathway (i.e., higher impulsivity and increased sensitivity to the stimulating effects of alcohol) and a negative reinforcement pathway (i.e., higher anxiety and increased sensitivity to the anxiolytic effects of alcohol) that may link sleep disturbances and alcohol problems. We will use a rigorous multi-method approach that extends the laboratory into the real world. Results may directly inform AU treatment by identifying which specific sleep factors contribute to risk and why. Aims: For the positive reinforcement pathway, we hypothesize that later sleep timing and shorter sleep duration will predict higher impulsivity and greater increases in impulsivity and stimulation while intoxicated. For the negative reinforcement pathway, we hypothesize that lower sleep efficiency, a marker of insomnia, will predict higher anxiety while sober and increased anxiolytic response to alcohol. These processes will account for the association between sleep factors and concurrent and prospective AU outcomes. Specificity of the positive and negative reinforcement pathways will be examined. We will also explore if sex or diagnostic status (alcohol use disorder (AUD), sleep disorders) moderate the relationships between sleep characteristics and reinforcement pathways to AU. Approach: Young adult drinkers (21-30 years of age; 50% female; N = 150) will complete a protocol that includes ecological momentary assessments (EMA), laboratory sleep and alcohol response assessments, and 6-month follow-up. Participants will be current heavy episodic drinkers (i.e., 5+ days in past 30 days of consuming 5+/4+ for males/females; SAMHSA) to ensure sufficient range in alcohol outcomes of interest. We will use two 10-day EMA/actigraphy protocols to track daily sleep characteristics (timing, duration, and efficiency), anxiety, AU (freq. of 5+/4+ drinks/occasion), impulsivity, and subjective alcohol response in the real world. Each EMA protocol will conclude with an overnight sleep laboratory assessment followed by a within-subjects laboratory alcohol administration (counterbalanced: placebo/alcohol sessions) to examine alcohol response. During the chronobiology lab visits, we will use salivary DLMO to assess physiological circadian timing. During the alcohol lab visits, we will measure positive and negative reinforcement pathways via subjective response (stimulation/anxiety) and impulsivity (self-report, tasks). A 90- day timeline follow-back interview delivered 6 months later will allow for the prospective examination of associations between sleep characteristics and later AU (freq. of 5+/4+ drinks/occasion) and problems. The proposed study will provide novel information about how sleep disturbances, a set of modifiable factors, affect alcohol response and impulsivity. These findings may directly translate to prevention/treatment efforts for AUD.

Project Summary Significance: Black drinkers experience more alcohol problems than White drinkers even at equivalent levels of alcohol use. These problems are pervasive, occurring across physical, social, and legal outcomes. The reasons that explain why Black drinkers are at elevated risk for experiencing alcohol problems are understudied and not well understood, but may involve differences in level of stress and acute response to alcohol. The proposed R01 examines these constructs both within the laboratory and in the natural environment using ecological momentary assessment (EMA) to identify proximal points of intervention for both Black and White drinkers. Aims: Aim 1 will examine racial differences in the anxiolytic effects of alcohol prior to and after a stress induction in the lab. Aim 2 will directly test if differential alcohol response measured in the lab strengthens the association between stress and alcohol cognitions (craving for alcohol, drinking motives), and accounts for racial differences in these cognitions. Aim 3 will examine the extent to which lab-based alcohol response and daily reports of stress explain racial differences in alcohol problems through 12-month follow-up. Hypotheses: We hypothesize that Black drinkers will have increased sensitivity to the anxiolytic effects of alcohol compared to White drinkers and that this sensitivity to alcohol as well as elevated stress will predict increased risky alcohol cognitions in EMA. Additionally, the association between stress and alcohol cognitions will be stronger for participants with the most sensitivity to the anxiolytic effects of alcohol. EMA alcohol cognitions will partially account for the association between alcohol response, stress, and alcohol problems during the EMA period and at the 6- and 12- month follow-ups. These processes and their transaction will partially account for why Black drinkers, relative to White drinkers, experience more alcohol problems. Approach: Young adult drinkers (N = 280; 21-30 years of age; 50% Black, 50% female) will be recruited from the community. Participants will first complete a semi-structured diagnostic interview and questionnaires and will then complete two laboratory sessions (placebo and alcohol; randomized order) with a standardized stress task to assess acute alcohol response. Next, participants will complete a 17-day EMA protocol to record fluctuations in stress, alcohol cognitions, alcohol response, alcohol use/problems. To allow for the prediction of prospective outcomes follow-up assessments at 6- and 12- months will be conducted and will include past 6 month self-reported alcohol use, alcohol problems, stress, and alcohol cognitions, as well as a 90-day timeline follow-back interview. This R01 proposal is directly in line with the NIAAA's strategic priorities to understand the role of stress in relation to alcohol problems and to decrease health disparities. The proposed research takes a critical step towards increasing our understanding of why Black drinkers are at greater risk for alcohol problems and will ultimately inform intervention efforts that are tailored to this under-studied, at-risk, population.

Project Summary Significance: Black relative to White young adults engage in heavier marijuana (MJ) use and are more likely to experience cannabis use disorder. The reasons for these disparities, including the role of stress caused by racism, are poorly understood and in critical need of empirical study. The proposed R01 examines the dynamic transactions between stressors, emotional reactivity, and MJ cognitions (craving, motives) within the laboratory and in the natural environment using ecological momentary assessment (EMA), to identify the processes that contribute to these health disparities. Aims: Aim 1 will examine racial differences in MJ cognitions, craving and motives, acute MJ effects, and MJ problems. Aim 2 will test if emotional reactivity tightens the association between experiencing a stressor and MJ cognitions and if this process differs across race. Aim 3 will examine prospective associations at the 6-month follow-up to examine the transactional nature of these processes. Hypotheses: We hypothesize that Black relative to White MJ users will report higher MJ craving and coping motives, greater acute MJ effects (indexed by reductions in negative mood) and more MJ problems. These differences will be partially driven by chronic and acute stressors, including institutional racism and discrimination events. Additionally, the association between stress exposure and MJ cognitions will be stronger for participants with higher emotional reactivity and within-person on days with heightened emotional reactivity. The role of emotional reactivity in this process will be more pronounced for Black MJ users. Black more than White MJ users will increase their MJ use at the 6-month follow-up and this increase will be partially driven by higher baseline MJ cognitions and acute MJ effects. Increases in MJ use from baseline to 6-month follow-up will be associated with heightened emotional reactivity at 6-month follow-up. In turn, heightened emotional reactivity will relate to tightened associations between acute stress exposure and MJ cognitions during the 6- month EMA. Approach: Young adult MJ users (weekly+ MJ use freq.; N = 440; 18-25 years of age; 50% Black, 50% female; matched across race on past 30-day MJ use freq.) will be recruited from the community. Participants will first complete a interview/questionnaires and a standardized stress task to assess emotional reactivity (subjective, physiological: HRV, HF-HRV) and craving. Next, participants will complete a 17-day EMA protocol to record stress and discrimination events, emotional reactivity (subjective and physiological), MJ cognitions, MJ use/problems. A parallel lab and EMA follow-up assessment will be completed at 6- months. This proposal is directly in line with NIDA?s strategic priorities on increasing health equity and NIDA?s focus on addressing real-world complexities that contribute to substance use problems. The proposed research takes a critical step towards increasing understanding of why Black young adults are at greater risk for heavy MJ use and problems and can inform intervention efforts tailored to this under-studied, at-risk, population.

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.