Carla K. Danielson, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): This proposal for a Mentored Patient-Oriented Research Career Development Award is intended to develop the career of Carla Kmett Danielson, Ph.D. as a clinical researcher in the field of risk reduction for drug use and sexual revictimization in adolescent sexual assault victims. The training and research plan proposed in the current application will build on Dr. Danielson's prior experience in child clinical psychology, traumatized populations, and treatment of high risk adolescents. The training has five components: 1) Mentoring and formal training experiences with senior scientists whom will serve as sponsors: Dr. Heidi Resnick as primary sponsor and Drs. Scott Henggeler and Cynthia Cupit Swenson as secondary co-sponsors; 2) Formal coursework and tutorials in qualitative and biostatistical analysis, substance abuse, design and conduct of clinical trials, protection of human subjects in clinical research, and the Spanish language; 3) Design and execution of a research project: a) Developing an early intervention, Risk Reduction through Family Therapy (RRFT), for adolescent sexual assault victims by adapting and integrating empirically-supported interventions that target substance abuse, trauma-related symptoms, and revictimization risk; b) Testing the feasibility of the application of RRFT through a pilot feasibility trial; c) Evaluating the efficacy of RRFT by conducting a small randomized clinical trial; 4) Training in recruitment and retention of Hispanic adolescent sexual assault victims and their families for such risk reduction-based treatment; 5) Preparation of an R21 and an R01 grant application based on the training and research that is performed during the award period. The proposed research plan will adhere to the treatment development recommendations made in the Stage Model of Behavioral Therapies (Onken, Blaine, & Battjes, 1997), with a focus on Stage 1a and 1b research. The activities performed during the award will provide the training necessary for the applicant to transition into an independent substance abuse patient-oriented researcher specializing in the areas of adolescent sexual assault and treatment. The proposed project has implications for several ongoing public health problems, particularly the high rates of adolescent substance abuse in the United States and the negative sequelae related to substance abuse in this vulnerable population. Specifically, by reducing risk of substance abuse in adolescent sexual assault victims, their risk of revictimization, HIV sexual risk behaviors, and mental health problems resulting from the sexual assault also likely will be reduced. Further, the proposed training and research in this application related to the recruitment and retention of Hispanic families will help address health care disparities in this traditionally underserved population. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Disaster-exposed youth, in comparison to adult samples, are at significantly greater risk for Posttraumatic Stress Disorder (PTSD), with symptoms often persisting for many months and years post-disaster. However, other disaster-exposed youth show resilience and rapid recovery without PTSD development. Efforts have been initiated to identify specific PTSD risk and resiliency factors;however, this work has relied largely on self- report strategies. Although useful in many circumstances, the sole reliance on self-report for identified PTSD risk and resiliency factors can be problematic. Thus, the development of innovative behavioral technologies that draw upon the methods of translational research and experimental psychopathology, and that assess specific risk and protective factors not easily or reliably measured through self-report, would be a valuable contribution to PTSD risk assessment. In the current study, we propose to develop and evaluate a state of the art comprehensive tool for PTSD risk assessment among disaster-exposed youth through the use of novel behavioral assessment tasks targeting two factors theoretically and empirically linked with PTSD (distress tolerance and risk-taking propensity), in combination with the use of other empirically identified disaster, child, and parent risk factors. If successful, this tool will help improve the understanding of more basic mechanisms underlying the development of PTSD in relation to disaster-related trauma, and potentially to other types of trauma, and also will likely aid in targeted early intervention development, modification, and implementation efforts. To accomplish these goals, this project will recruit a population-based sample of 3,000 disaster- exposed youth and their parents participating in an NIH-funded longitudinal, web-based intervention study (R01MH081056). Youth and parent participants will complete an initial phone-based, baseline assessment, where information regarding disaster exposure, other traumatic event experiences and incident characteristics, family-related variables, and PTSD and other mental health symptomatology will be gathered. Participants also will be asked to complete an additional web-based assessment following the baseline interview, which will involve both youth and parents completing novel computerized behavioral assessment tasks targeting distress tolerance and risk-taking propensity, as well as an additional self-report measure of trait anxiety. Phone-based interviews will be readministered at four- and twelve-months post-baseline to reassess PTSD symptoms. Sophisticated statistical procedures, including Receiver Operating Characteristics Tree methods, will be used to further examine the relation between the factors assessed and PTSD symptoms, to determine sensitive and specific cut-scores on the aforementioned tasks, measures, and variables for clinical decision-making, and to develop a decision algorithm that includes all significant PTSD predictors. Specifically, we seek to create an optimized, staged approach to PTSD risk assessment that balances accuracy against feasibility and costs to provide a practical, functional assessment battery that will generalize to multiple clinical settings. Given the high prevalence of disasters world-wide and the costly, debilitating impact of PTSD on disaster- exposed youth and their families, the proposed work is highly relevant to public health needs. Specifically, if successful in attaining the aims proposed for the current study, the sophisticated development of a PTSD risk assessment clinical tool would aid in the accurate and cost-effective identification of youth who are at greatest risk for PTSD. Such identification would help target post-disaster risk-reduction efforts and would likely reduce the incidence of full diagnostic PTSD and its associated costs and suffering.

Individuals exposed to a traumatic event at any time in their life, particularly those who develop posttraumatic stress disorder (PTSD), have a higher incidence of problematic drinking. However, little is known about the relationship between trauma, PTSD, and drinking in "emerging adults" (ages 21-30 years), in spite of this age group being at highest risk of developing subsequent drinking problems. The proposed clinical laboratory project will use a three group design. The target population will have no trauma exposure [Control group], trauma exposure without PTSD [TE group], and trauma exposure with PTSD [PTSD group]. The type of traumatic event exposure history included will be limited to interpersonal trauma. This project will use a well-established clinical laboratory paradigm of stress induction employed during the current Center funding period, the Trier Social Stress Test (TSST), to investigate the role of a history of exposure to trauma on reactivity to the TSST and on stress-induced voluntary drinking. Subjects will not meet diagnostic criteria for alcohol dependence. Half of each group will receive the TSST and the other half will be randomized to the no stress condition. Using subjective as well as biological indices of stress, the first specific aim examines the effect of trauma history on stress reactivity, using subjective, neuroendocrine, and physiological measures of stress. The second specific aim will examine the effect of trauma history on subsequent drinking behavior and subjective response to alcohol using established procedures in a clinical laboratory paradigm. Exploratory analyses will also be conducted to examine the correlation between trauma history group and subjective response to stress, and trauma history group and drinking. Two additional exploratory analyses will evaluate the effect of the personality trait of distress tolerance (high and low), and the effect of carrying the 'S'or the rare 'L{G}'allele of the 5-HTTLPR polymorphism on the stress response and on voluntary drinking following stress induction. This study will advance our understanding of the relationship between a history of interpersonal trauma, stress, and drinking. The ultimate goal of this line of research is to identify "at risk" groups early in their drinking careers, before unhealthy drinking practices and/or dependence develop. This information has the potential to inform prevention and intervention alcohol research.

Child Sexual Abuse (CSA) is one of the strongest and most consistent predictors of adolescent problems. Youth who have experienced CSA are at significant risk for early initiation, use, and abuse of substances. For example. research has indicated that adolescent CSA victims are over 3.5 times more likely to report marijuana abuse/dependence compared to non-CSA victims. Other negative sequelae, such as posttraumatic stress disorder (PTSD) and HIV sexual risk behaviors, also have been clearly linked with CSA. Remarkably, no behavioral interventions have been developed and rigorously evaluated for this population that: a) take an integrated approach to targeting such sequelae through use of existing empirically supported interventions; and b) incorporate risk reduction for less symptomatic youth. Risk reduction and treatment tailored to adolescent CSA victims, which addresses the individual, family, and community risk and resiliency factors for adolescent substance use problems and incorporates exposure-based treatment for PTSD symptoms, as well as evidence based prevention interventions for HIV-related sexual behaviors, and is warranted. Risk Reduction through Family Therapy (RRFT) has been developed by the PI, a NIDA-K awardee (K23DA018686) and Early Stage Investigator, for this purpose. Preliminary findings from a Stage 1a feasibility trial and a Stage 1b pilot randomized controlled trial (RCT) are promising, indicating that RRFT can be readily learned and implemented with fidelity, and that it can lead to improvements in drug use and drug use-related risk and protective factors, PTSD symptoms, and HIV sexual risk behaviors (Danielson et al., 2010). In following NIDA's recommended stage model of behavioral therapy development, the overall goal of this application is to conduct a Stage II RCT to more rigorously evaluate the efficacy of RRFT (vs. Treatment As Usual) from pre-treatment through 18 months. The first specific aim of the proposed study is to evaluate the efficacy of RRFT in reducing substance use problems and prognostic factors among CSA victims experiencing trauma-related symptoms. The second specific aim is to evaluate the efficacy of RRFT in reducing PTSD and HIV sexual risk behaviors among this population. In order to better make maximum use of the data from this proposed efficacy trial and to inform potential next steps in this line of treatment research (per NOT-DA-019), preliminary investigation on mechanisms of action in RRFT also will be pursued as an exploratory aim. Specifically, intermediate targets of RRFT, such as parenting practices and emotional reactivity, as putative mechanisms of action for improvements in substance use and PTSD and risky sexual behaviors will be explored. The results of the proposed study will have a significant impact on public health by informing intervention efforts for the multifaceted clinical needs of adolescent CSA victims, who are at high risk for drug use, HIV infection, other problems in adolescence and adulthood. Demonstrating the efficacy of this promising risk reduction and treatment approach could provide a valuable clinical tool for community-based therapists.

DESCRIPTION (provided by applicant): This application proposes a 5-year continuation (Yrs 26-30) of an NIMH National Research Service Award (T32 MH018869) entitled, Traumatic Stress Across the Lifespan: A Biopsychosocial Training Program, at the Medical University of South Carolina. We seek support for 6 postdoctoral positions per year and anticipate each postdoctoral appointment will be for 2 years. The primary goal of this training program is to provide postdoctoral fellows (PhDs, MDs or MD/PhDs) with the research acumen, resources and career opportunities necessary for their development into productive, independent clinical scientists, conducting traumatic stress- related mental health research of high

? DESCRIPTION (provided by applicant): The purpose of this K24 proposal is to enhance exponentially Dr. Carla Kmett Danielson's mentorship and research program in innovative approaches to risk reduction of HIV infection and addiction among adolescents, with a particular focus on trauma-exposed populations. Dr. Danielson, a clinical psychologist and scientist, is the ideal candidate for this mechanism. She has sustained continuous federal-funding of her patient oriented research (POR) since 2005, which has provided the framework for her mentorship of 19 junior investigators contributing to the science of substance abuse comorbidity with high-risk sexual behaviors and trauma. Her mentees, who have included early career faculty, postdoctoral fellows, and predoctoral psychology interns, have made significant contributions to the HIV prevention, substance abuse, and traumatic stress fields through high-impact publications and independent lines of NIH-funded research. Dr. Danielson's long-standing dedication and achievements in POR mentorship are further evidenced through her leadership roles as PI of an NIH-funded T32 Program dedicated to clinical research training in traumatic stress and its sequelae across the lifespan and as Co-Chair for the Faculty Mentorship Program in MUSC's Department of Psychiatry and Behavioral Sciences (currently ranked 7th in the country for NIH funding). The proposed K24 award will be essential in providing time and resources necessary for the candidate to formalize, expand, and sustain her mentoring program and capacity, further stimulate the research program of her mentees (e.g., through a proposed trainee pilot award program and new training opportunities) and augment her research skills and growing program of research in e- and m-health technologies for traumatized adolescents at risk for HIV infection and addiction. Innovative research proposed by Dr. Danielson under the K24 involves development and evaluation of a dynamic, technology-based prevention tool-kit (electronic HIV-sex Education and Addiction Risk for Traumatized Teens; eHEARTT). The toolkit will enhance the quality, accessibility, and efficacy of HIV- risk and substance use prevention interventions for adolescents receiving trauma-focused treatment. Specific aims of the research are to: 1) Develop the eHEARTT toolkit to support delivery of evidence-based HIV and substance use prevention interventions during the delivery of trauma-focused treatment (TF-CBT); 2) Conduct usability tests of the eHEARTT toolkit with teens, caregivers, and clinicians to guide refinements; and 3) Conduct a randomized controlled feasibility trial with 40 families to evaluate TF-CBT plus eHEARTT in comparison to TF-CBT plus a risk behavior electronic Resource List through a 6-month post-treatment follow- up assessment. These aims harmonize well with Dr. Danielson's proposed mentorship activities and current federally-funded research projects in the areas of HIV prevention, substance use risk reduction, and trauma among teens. The proposed research affords rich training opportunities for her mentees (early career faculty, postdoctoral fellows, and predoctoral psychology interns with an emphasis on trainees from groups under- represented in clinical science) and will invigorate new directions in POR with teens at risk for HIV infection and addiction. The proposed work is directly in line with NIDA priorities and funding announcements that call for research designed to evaluate the application of new technologies for delivering adapted prevention interventions targeting drug and alcohol use and prevention of HIV acquisition.

Interpersonal violence (IPV) exposure affects 1 in 2 youth and levies tremendous physical and mental health burdens on victims and society. Childhood IPV exposure is a well-established risk factor for anxiety and other mental health problems across the lifespan. There is great variability among youth in the nature and timing of IPV exposure and considerable heterogeneity in mental health outcomes. Such heterogeneity in outcomes may be explained by various Research Domain Criteria (RDoC) constructs, including Negative Valence Systems (NVS) involving responses to threat. That is, disruptions in the functioning and development of neural and physiological systems associated with threat processing may account for heightened anxiety symptoms commonly observed following IPV. A paucity of longitudinal studies assessing multiple threat-related mechanisms, across multiple units of analysis, and at key times in development has been a critical barrier to informing the design of personalized treatments to target root causes of post-IPV psychopathology. The overarching goal of this project is to examine developmental trajectories of threat-related NVS measures into adolescence, as a function of exposure to IPV, in an effort to better link IPV and anxiety through changes in these measures. The specific aims of this project are: 1) to identify threat-related NVS constructs that connect lifetime IPV to anxious symptoms in youth cross-sectionally; 2) to investigate longitudinally the degree to which IPV sensitizes trajectories of NVS measures over a two-year period across three age cohorts (grades 3, 6, 9 at baseline); and 3) to investigate the degree to which trajectories of NVS measures predict anxiety symptoms over a 2-year period after accounting for initial anxiety symptoms and IPV status. An exploratory aim is to examine how amygdala activity and ACC functioning at baseline and overtime predict changes in other threat- related NVS measures (ERP, startle, ERN, cortisol reactivity) over time. To accomplish the aims, the approach involves studying the contributions of three threat-related NVS constructs, including responses to acute threat, potential threat, and sustained threat. These constructs will be measured across multiple units of analysis (neural circuitry, physiology, behavior/self-report) and over time using a battery of well-validated translational neuroscience laboratory paradigms and assessment tools. An accelerated longitudinal cohort design will be used to test key developmental questions (e.g., whether pubertal status moderates the effect of IPV on potential threat or sustained threat). Three cohorts of children (total n=360) and their caregivers will be enrolled and prospectively across 3 annual in-person lab assessments, with phone-based assessments in between. A community sample representing a broad continuum of IPV experiences and a wide range of anxiety symptoms will be recruited. By studying multiple NVS constructs over time across multiple units of analysis, findings will clarify the timing and developmental course of psychobiological vulnerabilities to anxiety problems in IPV- exposed youth, and will impact clinical care and future clinical research classification.  

Project Summary The primary goal of this unique training program is to equip postdoctoral fellows with the research skills, resources, and career opportunities necessary for their development into independent clinical scientists producing mental health research that will have a sustained influence on the traumatic stress field. The NIMH T32 Traumatic Stress Research Program, housed in the National Crime Victims Research and Treatment Center (NCVC) at MUSC, has trained postdoctoral fellows in state-of-the-art scientific methods in basic and translational traumatic stress research?in both child and adult populations?for the past 29 years. This application proposes 5 years continuation (Years 31 through 35) of this program, in which support is sought for five postdoctoral positions of two-year duration. Through mentorship and training with a large number of talented and prolific faculty who have made a career commitment to traumatic stress-related mental health research and its associated sequelae, the objectives of the program are to develop competence in several areas, such as: (1) sampling methods and data collection modes; (2) familiarity in the measurement and integration of neural, psychophysiological, and genetic units of analysis; (3) foundational skills in working with `big data'; (4) evaluation and dissemination of evidence-based interventions; (5) ethical and cultural issues in trauma research; and (6) translating findings to inform public policy. Fellows will select specialized training in one of two tracks ? Epidemiology Risk and Resiliency (ERR) research or Treatment Development, Evaluation, and Dissemination (TED) research. Training will be outlined in each fellow's Individualized Development Plan and guided by the fellow's selection of a Primary Mentor in the area of traumatic stress and a Secondary Mentor from among other MUSC faculty and additional academic institutions. Secondary Mentors add great breadth to training opportunities through their complementary expertise in areas of translational or clinical science spanning: addiction, brain stimulation, neuroimaging, genetics, dissemination and implementation science, minority health disparities, psychopharmacology, and HIV prevention. Fellows also will benefit from a full array of core, selective, and elective training options that include formal course work, workshops, training in the responsible conduct of research, disability training to enhance diversity, and retreats. The caliber of the training program is clearly reflected in the record of notable accomplishments and scientific contributions made by its previous fellows, both within the most recent 5-year funding period and over its 29-year duration: 100% of postdoctoral fellows who have completed training over the most recent renewal funding period and > 90% of trainees who have completed the Program in the past 15 years are employed in research positions. A primary strength of the training program is the innovative program of research among the NCVC and affiliated T32 faculty that includes a number of ongoing, federally-funded projects that address some of the most significant questions facing the traumatic stress field and that closely align with NIMH Research Strategic Priorities.  

Interpersonal violence (IPV) exposure affects 1 in 2 youth and levies tremendous physical and mental health burdens on victims and society. Childhood IPV exposure is a well-established risk factor for anxiety and other mental health problems across the lifespan. There is great variability among youth in the nature and timing of IPV exposure and considerable heterogeneity in mental health outcomes. Such heterogeneity in outcomes may be explained by various Research Domain Criteria (RDoC) constructs, including Negative Valence Systems (NVS) involving responses to threat. That is, disruptions in the functioning and development of neural and physiological systems associated with threat processing may account for heightened anxiety symptoms commonly observed following IPV. A paucity of longitudinal studies assessing multiple threat-related mechanisms, across multiple units of analysis, and at key times in development has been a critical barrier to informing the design of personalized treatments to target root causes of post-IPV psychopathology. The overarching goal of this project is to examine developmental trajectories of threat-related NVS measures in adolescence, as a function of exposure to IPV, in an effort to better link IPV and anxiety through changes in these measures. The specific aims of this project are: 1) to identify the threat-related NVS mechanisms that connect IPV to anxious symptoms in youth cross-sectionally; 2) to investigate longitudinally the degree to which IPV sensitizes trajectories of NVS measures over a three-year period; and 3) to investigate the degree to which trajectories of NVS measures predict anxiety symptoms over time after accounting for initial anxiety symptoms and IPV status. An exploratory aim is to identify moderators (e.g., puberty) of IPV, threat-related NVS, and anxiety symptom associations. To accomplish the aims, the approach involves studying the contributions of three threat-related NVS constructs, including responses to acute threat, potential threat, and sustained threat. These constructs will be measured across multiple units of analysis (neural circuitry, physiology, behavior/self-report) and over time using a battery of well-validated translational neuroscience laboratory paradigms and assessment tools (e.g., fMRI, EEG, startle, cortisol reactivity). An accelerated longitudinal cohort design will be used to test key developmental questions. Three cohorts of children (total n=360; grades 3, 6, 9 at baseline) and their caregivers will be enrolled and prospectively followed for 3 years. Consistent with RDoC priorities, a community sample representing a broad continuum of IPV experiences and a wide range of anxiety symptoms will be recruited. By studying multiple NVS constructs over time across multiple units of analysis, findings will clarify the timing and developmental course of psychobiological vulnerabilities to anxiety problems in IPV-exposed youth, impact clinical care and future clinical research classification, and test the validity of the RDoC threat-related NVS matrix (e.g., whether responses to potential vs. sustained threat are uniquely related to IPV and outcomes or explain the same variance) in youth.  

Psychosocial traumatic events, and interpersonal violence experiences in particular, during childhood serve as strong and consistent predictors of substance use problems (SUP) during adolescence and adulthood. PTSD that extends from such IPV often co-occurs with SUP. Despite this well-established link, standard care for adolescents with co-occurring SUP and PTSD for the last several decades has been to treat these problems separately. This compartmentalized approach to treatment creates burden on teens and families, raises unique challenges to clinicians in both mental health and addiction domains, and may contribute to high rates of SUP relapse among adolescents with co-occurring PTSD. To address this problem, our team recently completed a rigorous NIDA-funded randomized controlled trial (RCT) supporting the efficacy of an integrative, exposure- based treatment we developed, Risk Reduction through Family Therapy (RRFT), in greater long term reductions in SUP, as well as PTSD avoidance and hyperarousal symptoms, in comparison to standard treatment in a large teen sample. The proposed RCT, with an effectiveness-implementation Hybrid Type I design, substantially builds on that prior research by proposing to: 1) evaluate whether RRFT's clinical effectiveness for reducing SUP and PTSD can be extended to youth in outpatient substance use treatment settings?where youth are presenting for SUP treatment and where clinicians often have less experience treating PTSD (Aim 1); 2) evaluate the cost- effectiveness of RRFT and to explore inner context variables (e.g., perceived treatment acceptability, attitudes, and satisfaction among the participating adolescents, caregivers, agency leaders, and therapists and barriers to and facilitators of implementation) that might affect RRFT implementation in diverse practice settings (Aim 2). The proposed effectiveness-implementation trial will recruit adolescents (13-18 years) with a history of IPV presenting with SUP and PTSD symptoms for outpatient substance use disorder treatment at sites in Denver, Colorado affiliated with NIDA's Clinical Trials Network. Participants will be urn randomized to RRFT or Treatment as Usual. A multi-method, multi-respondent approach will track clinical outcomes (SUP, PTSD, and putative targets of treatment, such as emotional suppression) at 3, 6, and 12 months post-baseline. To reduce the science-to-practice gap, as an Exploratory Aim, we will assemble and engage an Advisory Board of leaders from Colorado state departments (Offices of Behavioral Health and Criminal/Juvenile Justice for Colorado, which have committed to participate) and community mental health organizations that oversee policy and decision- making in selection and implementation of psychosocial treatments for high-risk adolescents, with the goal of building capacity for large scale (e.g., state-wide) uptake of evidence-interventions for teen SUP and PTSD, like RRFT, upon completion of the grant. This proposal is directly in line with NIDA's recent release of NOT-DA-20- 004, a Notice of Special Interest encouraging research on comorbid substance use, substance use disorders, and other psychiatric disorders.