Wendy K. Silverman - US grants

The present proposal details a psychosocial treatment outcome study for childhood phobias, that draws upon psychological theories of fear reduction. Specifically, the study is concerned with devising and evaluating the relative effectiveness of two psychosocial treatments, a self-control and a contingency management program, against an educational-support comparison group. The contingency management program involves reinforcement for approach behavior, shaping, extinction, and repeated practice, and instruction. The self-control condition focuses directly on the modification of faulty cognitions. The study also compares the relative effectiveness of these two programs for children of varying ages (8 to 11 versus 12 to 15), both in the short term and in the long term, through systematic follow-up procedures. The ultimate goal of the research is the development of a psychosocial treatment, i.e., either contingency management or a self-control program, that can be used by therapists for purposes of childhood fear reduction, which has been proven to be relatively efficacious in treating simple phobia, in children of specific ages.

The proposed research project will experimentally test the effectiveness of Group Cognitive-Behavioral Therapy (GCBT) with anxiety disordered children. The specific disorders that GCBT targets include Social Phobia (SOP), Overanxious Disorder (OAD), and Avoidant Disorder (AVD). Recent surveys of the literature indicate that anxiety and phobic disorders of childhood and adolescence is one of the most prevalent if not the most prevalent disorder of childhood and adolescence. A total of 150 children (ages 8-12) and their parent(s) will be admitted to the study. Children who are admitted to the study will meet DSM-III-R criteria for a primary diagnosis of SOP, OAD, AVD. The proposed research study will use a pre-post experimental research design with a "waitlist" control group with random assignment to condition. The primary research question for the study concerns the effectiveness of GCBT relative to a waitlist control condition. Effectiveness will be evaluated on two levels: global and specific. First, the effectiveness of GCBT in reducing global level of distress as it interferes with overall functioning will be evaluated relative to the control condition. Second, the effectiveness of GCBT in reducing specific target symptomatology for SOP, OAD, AVD respectively will be evaluated relative to the control condition. Additional hypotheses will be tested with respect to variables that may either be related to or may moderate the effects of treatment. The data analytic strategies will include LISREL, repeated multivariate analysis of variance, and multivariate multiple regression analysis. A treatment manual (child and parent) has been developed for GCBT, thereby rendering the modality replicable by other researchers and accessible to clinicians upon its evaluation.

DESCRIPTION (Adapted from applicant's abstract): The proposed research project will experimentally test the effectiveness of parent-child Dyadic Cognitive Behavioral Therapy (DCBT) for children with anxiety and phobic disorders. DCBT is designed to enhance effectiveness relative to "standard" individual child treatment in both producing and maintaining treatment gains. DCBT is based on a "transfer of control" model for use in treating a broad spectrum of anxiety and phobic disorders in children. Briefly, this model is based on the premise that treatment effectiveness is maximized by the use of clear and direct pathways of transfer of control (in this case, from the therapist to the parent to the child). To render the pathways more clear and direct, this intervention systematically targets parent-child relational processes and parental anxiety and/or phobic disorders and/or symptoms (as necessary) in a dyadic format. A total of 120 children (ages 8-12) will be admitted to the study over the three years of the study. This study uses a clinical trials design with two conditions: 1) DCBT-Dyadic Cognitive Behavioral Treatment and 2) ICBT-Individual Cognitive Behavioral Treatment. The primary outcome analyses will evaluate the relative effectiveness of DCBT in terms of both producing and maintaining child treatment gains. Effectiveness will be evaluated on three levels: global child functioning, specific anxiety/phobic symptomatology, and parent-child relations. First, the relative effectiveness of DCBT in reducing specific children's global level of distress as it interferes with their overall individual functioning and positive end-state functioning will be evaluated. Second, the relative effectiveness of DCBT in reducing specific children's anxious/phobic symptomatology will be evaluated. Third, the relative effectiveness of DCBT in improving parent-child relations will be evaluated. Supplemental analyses will investigate the role of parent symptomatology, and therapist/client expectancies as predictors/moderators of treatment outcome. The data analytic strategies will include repeated multivariate analysis of variance, and multivariate multiple regression analysis. A treatment manual for the conditions has been developed and will be further refined during the course of the study, thereby rendering the intervention replicable by other researchers and accessible to clinicians. This treatment outcome study utilizes rigorous experimental controls and systemic follow-up procedures.

Considerable evidence has now accumulated demonstrating the efficacy of Individual Child Cognitive Behavior Therapy for reducing anxiety disorders in children. In growing recognition that the child's context affects the development, course, and outcome of childhood psychopathology and functional status, recent clinical research efforts have been directed toward evaluating whether cognitive behavior therapy when used with anxious children also is efficacious when particular contexts (i.e., family/parents, group/peer) are incorporated in the treatment program. As a result, there now exists considerable empirical evidence that childhood anxiety disorders also can be reduced in cognitive behavioral treatment programs that incorporate family/parents and peer/group contexts and target specific domains/content areas relevant to these contexts. Despite the above, there have been no studies that have directly evaluated whether family/parents and peer/group interventions that target specific domains/variables and content areas relevant to that respective intervention context actually produce specific effects on these domains/variables and, more importantly, whether changes produced on these variables mediate treatment response. Consequently, claims regarding the importance of incorporating (or not incorporating) family/parents and peer/groups and targeting respective variables relevant to each context in order to produce child treatment response are based more on speculation than on empirical data. Investigating whether incorporating family/parents or peer/group contexts and targeting specific domains/variables and content areas relevant to these respective contexts, and whether changes on these variables mediate treatment response in two cognitive behavioral treatments that each represent these distinct contexts (i.e., family/parents and peer/group) among children with anxiety disorders, thus comprise the specific aims of this project. The study targets the same DSM-IV anxiety disorders targeted in previous clinical trials and that are most common in children: social phobia, generalized anxiety disorder, and separation anxiety disorder. Using a controlled clinical trial design, 252 children (ages 8-14 years) and their parents will be admitted to treatment over the five years of the study, yielding an estimated 216 treatment completers at post-test and 180 at one year follow- up. Children and their parents will be randomly assigned to one of two treatment conditions: Family/Parents Cognitive Behavior Therapy (FCBT) and Peer/Group Cognitive Behavior Therapy (GCBT). All participants will be assessed at pretreatment, posttest, and one-year followup. Two sets of hypotheses will be tested. Because each condition represents a distinct treatment context (family/parents and peer/group) that targets the same two domains (skills and relationships) but in two different content areas within each domain (i.e., parenting skills and parent-child relationships in FCBT versus child social skills and peer-child relationships in GCBT), the first set of hypotheses is designed to establish empirically whether there are in fact treatment specific effects. Thus, the first set of hypotheses to be tested is that FCBT will produce significantly greater specific effects on parenting skills and parent-child relationships than on child social skills and peer-child relationships. GCBT, on the other hand, will produce significantly greater specific effects on child social skills and peer-child relationships than on parenting skills and parent-child relationships. The second and more theoretically and practically significant set of hypotheses will test whether or not it is the changes that are produced on these variables that mediate treatment response. Thus, the second set of hypotheses to be tested is that parenting skills, parent-child relationships, child social skills and/or peer-child relationships will be significant mediators of treatment response, i.e., anxiety reduction. To test the study's mediational models and to fully examine specificity effects, a multi-analytic approach that includes structural equational modeling and other complex data analytic strategies (e.g., growth curve modeling) will be used.

DESCRIPTION (provided by applicant): This is an application for a K24 Midcareer Investigator Award in patient-oriented research. The candidate is a tenured Full Professor of Psychology at Florida International University, Miami. She is Director of the Child and Family Psychosocial Research Center, which houses the Child Anxiety and Phobia Program, wherein she conducts her main research activities and mentoring. Career Development Goals: The K24 award will serve to (1) To enhance the candidate's knowledge and expertise of data analytic issues involved in patient-oriented research, particularly mediational analyses for use in clinical trials; and (2) To enhance her knowledge and expertise in engaging and mentoring psychology and child psychiatry trainees in clinical research, with an emphasis on female Hispanic trainees. The K24 would thereby serve to facilitate both the candidate's scientific career development and research mentoring. Mentoring Goals: The K24 award will serve to (1) facilitate the refinement of the mentoring mechanism that the candidate has successfully used to mentor patient-oriented psychology research trainees and extend it to minority trainees in both psychology and child psychiatry (2) to publish at least two multi-authored "state of the art" empirical papers per year, each with a psychology and a psychiatry trainee, as the first author. Research Goals: The candidate's current RO1, Therapy Specificity and Mediational Effects, will serve as the main platform for the proposed K24. This "next generation" RO1 goes beyond whether treatment works to why treatment works. The specific aims are to evaluate the possible mediational effects of family/parents and peer/group contexts on child anxiety treatment response. Because of the intricacies of the study, a complex analytic plan has been designed to analyze this study's data. With this K award, the candidate will have an opportunity to enhance her data analytic skills and her trainees will also participate in the process of learning the advanced data analytic procedures and techniques.

[unreadable] DESCRIPTION (provided by applicant): This application proposes a mediation-outcome research study evaluating the specificity, mediation, and treatment outcome enhancement of parent involvement for reducing anxiety disorders in children. The study targets the same DSM-IV anxiety disorders targeted in previous clinical trials and that are most common in children: social phobia, generalized anxiety disorder, and separation anxiety disorder. Using a controlled clinical trial design, 336 children (ages 8-11 years) and their parents will be admitted to treatment over the five years of the study, yielding an estimated 236 treatment completers at one year follow-up. Participants will be randomly assigned to one of the three treatment conditions. Two parent involvement conditions (1) ICBT+Parent Reinforcement Skills Training (ICBT+RFST) (i.e., increasing parental use of positive reinforcement and decreasing negative reinforcement) and (2) ICBT + Parent Relationship Skills Training (ICBT- RLST) (i.e., increasing parental autonomy granting and increasing parental child acceptance), and (3) a "basic" ICBT without additional parent involvement components as a baseline comparison condition. Children and parents will be assessed at pretreatment, midtreatment, posttreatment, and one-year follow up with questionnaire measures, the child and parent versions of the interview schedules, and observational measures. Three sets of hypotheses will be tested. The first set tests for "specificity of effects," i.e., whether the addition of specific treatment components has the expected specific effects on the appropriately targeted parenting skills; the second set for "mediation," i.e., whether the effects of changes in the hypothesized mediators are related to significant positive change in child treatment outcome. The third set tests for differential treatment outcome (i.e., whether positive change in child treatment outcome in the parent involvement conditions is significantly greater than positive change in child treatment outcome in the ICBT treatment condition, a baseline comparison condition).The multi-analytic strategies that will be used in the analysis of the data (including structural equation modeling and other complex data analytic strategies e.g., growth curve modeling) are described in detail under the Data Analysis Plan. This application proposes a mediation-outcome child anxiety treatment study that evaluates the specificity, mediation, and treatment outcome enhancement of two distinct strategies for involving parents in their child's treatment relative to individual treatment. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): This application proposes a pilot test of Attention Bias Modification Training (ABMT) among children and adolescents who have completed a full protocol of cognitive behavior therapy (CBT) for anxiety and still meet criteria for a primary diagnosis of Social Phobia (SOP), Separation Anxiety Disorder (SAD), or Generalized Anxiety Disorder (GAD) a full year after completion of CBT. There is currently not a single empirical study in the youth anxiety treatment literature that has systematically examined a treatment augment for youth who fail to respond to a full course of CBT. Empirical efforts to address this issue are important because youths who do not respond to CBT continue to suffer emotional distress and impairment associated with anxiety disorders, experience frustration and demoralization by perceived failure, and likely pose a financial burden on the health care system. ABMT is a novel translational treatment for anxiety based on experimental and neuroscience research findings on attention processes. Research demonstrates that ABMT leads to reductions in anxiety and its disorders. Based on recent theory and research demonstrating an attention bias toward threat predicts CBT nonresponse among anxious youth, researchers have postulated that ABMT may hold promise as an augment to CBT because of its specific focus on attention bias that targets both frontal-cortical and subcortical circuitry. Thi study will recruit an estimated 70 children and adolescents who have completed a 12-14 week CBT trial for anxiety disorders (Silverman, R01 MH079943) and at the one year follow-up continue to meet criteria for a primary diagnosis of SOP, SAD, or GAD. These 70 children and adolescents (ages 8-16 years) will be randomly assigned to complete eight biweekly sessions of either ABMT or a placebo control (PC) task. Clinician ratings on youth anxiety severity will be collected and evaluated as the primary outcome. Youth self ratings on anxiety symptoms and parent ratings on youth anxiety symptoms will be collected and evaluated as secondary outcomes. All measures will be collected before condition assignment (pretreatment), at immediate posttreatment, and at an eight week follow up. The following specific aims will be addressed. Aim 1: Test whether ABMT leads to significantly lower levels of anxiety at posttreatment as compared to a Placebo Control Task. Aim 2: Examine whether ABMT leads to significantly lower levels of anxiety as compared to a Placebo Control Task at a follow up evaluation eight weeks posttreatment. This would suggest the maintenance of ABMT effects after eight weeks of no treatment. Aim 3: Gain perspective on the viability of variables as potential mediators and moderator of ABMT so as to inform decisions about whether to pursue these variables in a future R01. The variables proposed as potential mediators are attention bias toward threat and threat-related interpretation bias. The variable proposed as a potential moderator is attention control. Overall, this project will provide critically needed data on ABMT as a treatment augment for youth with anxiety disorders who do not respond CBT. With these data in hand, the field will be in a better position to determine whether and how ABMT may be used optimally among anxious youth who are likely to need more than CBT.

Project Summary This is an exploratory/developmental research proposal which seeks to build on and to enlarge our data into the role of fibroblast growth factor 2 (FGF2) in Fear (Acute Threat) and Approach Motivation, two constructs within the Negative Valence System and Positive Valence System, respectively, in the NIMH Research Domain Criteria (RDoC) project. FGF2 is one of a family of growth factors that impact neural development and that play neuromodulatory roles throughout life, shaping the organism's response to the environment. Disruptions in the Negative Valence and Positive Valence Systems characterize anxiety and depressive disorders, which account for the majority of psychiatric disability over the lifespan. The animal and sparse adult human studies implicating FGF2 in models of anxiety and depression led to FGF2's inclusion in RDoC as a target biological unit of analysis of the Fear construct. We know of no study that has examined FGF2 in humans with anxiety and its disorders, nor do we know of a study that examined FGF2 in clinical and nonclinical pediatric samples, anxious and/or depressed. Our team collected pilot data of FGF2 levels in a clinical sample of 50 anxious and depressed children and their mothers in addition to self-report and behavior data that corresponded with Fear, and Approach Motivation, respectively. We examined the associations between FGF2 levels, self-reports, and behavior in the children and mothers and found significant associations between the measurement units, and in the expected directions. These data, consistent with the animal and human studies, suggest FGF2 may play a role in modulating Fear, and Approach Motivation, which can lead to exciting, new research directions. We have since accumulated serum samples in 150 anxious and/or depressed children and mothers, and self-report and behavior data. We request R21 funds to conduct immunoassay analysis to measure FGF2 concentrations in this sample data. We also propose to broaden our sampling frame by collecting FGF2, self-report, and behavior data on 100 additional children who represent ?normal? controls, and subclinical or subthreshold anxiety and/or depression, and mothers. With these cumulative, dimensional data, we will study these measurement units' associations with Fear, and Approach Motivation in a measurement model using confirmatory factor analysis. Our final, exploratory aim is on the question of stability of FGF2, in relation to self-reports and behavior.

ABSTRACT Childhood obesity is a significant public health problem that predisposes to adult obesity and serious obesity-related diseases. Obesity is particularly common in low-income families and children of obese parents, who also report higher levels of stress. High stress in parents is associated with decreased physical activity, overeating, and increased weight in parents and their children. While nutrition and behavioral preventions have been tested for low-income families, parent stress has not been targeted in highly stressed, low-income obese parents of at-risk preschoolers. In a previous pilot R21 project, we developed a novel program, Parenting Mindfully for Health, that targets parent stress and includes Nutrition and physical activity counseling (PMH+N), to reduce stress, improve parenting and healthy family choices to prevent childhood obesity in 2-5-year-old children. Findings indicated that PMH+N is feasible, acceptable, and improved parent stress and parenting to prevent increases in child body mass index (BMI) percentile relative to the contact Control with Nutrition (C+N). Building on promising preliminary findings, we now propose a 5-year R01 project to assess PMH+N vs. C+N in a large sample of parent-child dyads, and including a long-term 2-year follow-up to establish enduring effects of PMH+N on reducing parent stress, improving parenting to promote healthy eating and physical activity (PA) in parents and children, and in turn, prevent childhood obesity risk in preschoolers from highly-stressed, low- income families. Low-income, highly-stressed, obese parent-child dyads (N=240, children aged 2-5) will be randomly assigned to receive a 12-week PMH+N or C+N intervention and participation in a Toy Wait Task(TWT) challenge to assess observed parent-child interaction as a bio-behavioral measure pre/post intervention to assess parenting and stress responses. The following specific aims will be addressed: (1) test the efficacy of 12-week PMH+N vs. C+N in reducing parent stress and improving parenting and health behaviors in parent and child to decrease childhood obesity risk; (2) examine parent stress response, observed parenting, and family food intake and physical activity as mediators of PMH+N vs. C+N effects on parent and child BMI; (3) examine the enduring effects of PMH+N vs. C+N on parenting and health behaviors and child BMI percentile in reducing obesity risk over a 2-year follow-up period; and (4) examine the enduring effects of changes on parent stress, parenting and health behaviors, parent weight and metabolic functioning post intervention during 2-year follow-up. Successful completion of the proposed interdisciplinary project will provide support for an innovative approach to decrease early childhood obesity risk in low-income, stressed families while also addressing stress and obesity in high-risk adult parents. Findings will provide critical longitudinal data on parent stress and family and parenting factors in the development of obesity in at-risk children, that may inform future public health interventions to curb the growing epidemic of obesity in children and adults.

Project Summary This 2-site (Florida International University, Yale University) R01 project proposes to confirm attention bias modification treatment (ABMT) as an efficacious treatment for social anxiety disorder (SAD) in peripubertal youth ages 10 to 14 years, and examine the mechanisms of ABMT's clinical efficacy. SAD is prevalent, chronic, and impairing. Response rates to evidence-based treatments (EBTs) are markedly lower for SAD than other anxiety disorders, and limited insights exist about mechanisms of positive outcome for those youths who do respond to existing EBTs. Alternative treatment options are therefore critically needed, particularly for translational neuroscience approaches that arise from NIMH's experimental therapeutics approach. ABMT is such an approach, as it is grounded in cognitive neuroscience theory and methods to address perturbed attention that operates on extremely rapid time scales. In accordance with NIMH's experimental therapeutics approach, we collected data in our preliminary work that support ABMT's feasibility and acceptability, and identifies a putative target mechanism. We next collected data demonstrating an effect on the target (i.e., target engagement) and linking changes in the target to clinical improvements (i.e., target validation). Specifically, we collected data on targeted rapidly deployed processes in event related potentials (ERP), and found that youth with SAD show enhanced P1 amplitudes for socially threatening stimuli compared with typically developing controls, thereby indicating enhanced neural processing during attention orienting to social threat, providing a putative ABMT target. Our data further show ABMT to reduce both anxiety severity (i.e., signal of clinical efficacy) and P1 amplitudes, with these clinical and neural changes occurring together. These data position us to propose a confirmatory efficacy R01 to (1) re-demonstrate target engagement, (2) re-demonstrate the effects of ABMT on social anxiety symptom severity, (3) demonstrate target validation, and (4) evaluate the maintenance of outcomes. We also will (5) explore attention control as a moderator of outcomes. We will randomize 260 (N = 130 at each site) clinic referred youths ages 10-14 years who meet for SAD to either ABMT or a Neutral Control Task (NCT). We hypothesize that attention orienting to social threat, measured using P1 ERP amplitudes in the dot-probe task, and social anxiety symptom severity will be significantly lower at post-treatment and 6-month Follow-Up in the ABMT arm compared with the NCT arm. We further hypothesize that P1 amplitudes will mediate reductions in social anxiety symptom severity. This project will provide a rigorous, sufficiently powered mechanistic test of ABMT for SAD in youth. Supportive findings would position us to pursue an effectiveness trial of ABMT in community and practice settings. Findings will also provide insight on attention control's promise for future research relating to precision medicine approaches.

Project Summary This 2-site (Florida International University, Yale University) proposed funded Administrative Supplement to Pettit/Silverman R01, Targeting Attention Orienting to Social Threat to Reduce Social Anxiety in Youth, aims to increase the sustained impact of the project and falls within the scope of the current award. Our primary aim is to collect Supplemental data to firmly establish stability of the study's putative target mechanism, the rapidly deployed attention-associated neural processes measured via event-related potentials (ERPs) (i.e., P1 amplitudes for socially threatening stimuli in peri-pubertal youth ages 10 to 14 years). We will collect Supplemental data using a broadened sampling frame of 70 additional youths (35 per site) across a continuum of social anxiety symptom severity, in line with the Research Domain Criteria (RDoC) framework. We will use the same Parent Grant assessment points: PRE, MID (two weeks after PRE), POST (four weeks after PRE), and FOLLOWUP (6 Months after POST). The Supplemental participants will be involved only in the study's assessment procedures, unlike Parent Grant participants who are randomized to either (1) Attention Bias Modification Treatment (ABMT) or (2) Neutral Control Task (NCT). We will evaluate (1) within-subject stability among the Supplemental participants who receive no intervention, and (2) between-subject stability by comparing Supplemental participant data with Parent Grant participant data. There has never been a stability study of our project's putative target P1 amplitudes for socially threatening stimuli in youth (or adults), aside from our preliminary data (test-retest reliability of r = .50 over 8 weeks). Collecting these Supplemental data is therefore critical to establish firmly the target's stability and will benefit the experimental therapeutics approach by providing novel confirmatory support for the mechanistic role of ERP P1 amplitudes in attention training protocols in a broad sample of youth whose social anxiety symptoms are assessed dimensionally. Data documenting within-subject stability among Supplemental participants, together with data from the Parent Grant demonstrating P1 reductions in youth who receive attention training, would provide novel convergent data, establishing more firmly the stability and plasticity of this target in the critical developmental window of peri-puberty. These data will further facilitate our efforts to translate ERP effects from the Parent Grant into clinically interpretable effects. This is because these Supplemental data from a broadened sample of youth across a continuum of social anxiety severity will provide a benchmark against which to compare ERP P1 amplitudes in youth with social anxiety disorder prior to attention training. They also will allow us to determine whether attention training in youth with social anxiety disorder results in ERP P1 amplitudes comparable with those found in a broadened, nonreferred sample of youth, and whether this occurs after 4 (MID) or 8 sessions (POST).