Tara S. Peris, Ph.D. - US grants

DESCRIPTION (provided by candidate): This is a request for a Mentored Patient-Oriented Research Career Development Award (K23). The candidate is a clinical child and adolescent psychologist whose long-term goal is to develop family-focused interventions to optimize treatment outcomes for youth with pediatric OCD and related disorders. Her more immediate career objective is to launch an independent patient-oriented research career by gaining specific training in developing standardized family-based interventions;clinical intervention trial design and implementation;and quantitative methods for assessing developmental processes and mechanisms of change in clinical trials. To accomplish these goals, the candidate's career development plan will consist of select coursework and tutorials as well as mentorship in the following areas: (1) Treatment development for family-focused interventions;(2) Clinical intervention trial design and implementation;and (3) Quantitative methods for analyzing longitudinal intervention data. Training in these three areas will facilitate the following specific research aims: (1) To refine treatment concepts and develop a formal manual for the Positive Family Interaction Therapy (PFIT) program;(2) To conduct an open case series using the PFIT manual;(3) To implement a small controlled trial of the PFIT intervention;(4) To practice the timing and assessment of putative family factors that serve as mechanisms of change in the treatment of pediatric OCD. RELEVANCE: Pediatric OCD is a pervasive, chronic, and highly impairing illness. Although cognitive behavioral and pharmacological therapies have proven efficacious, a large proportion of youth fail to respond to these treatments. Given this, the development of evidence-based treatments tailored to the needs of treatment refractory cases is a clear public health priority.

DESCRIPTION (provided by applicant): Families of youth with OCD are characterized by an array of stressful family dynamics that predict poor response to cognitive behavior therapy (CBT), the current treatment of choice for pediatric OCD. However, understanding of the specific mechanisms which family functioning interferes with treatment is limited. Youngsters in unstable home environments have been found to exhibit prolonged activation of stress response systems, and separate lines of research link this heightened reactivity to disrupted extinction learning and the maintenance of fear and avoidance behaviors. Thus, one possibility is that poor family functioning complicates specific tasks of CBT (e.g., exposure exercises, family disengagement from symptoms) via heightened stress reactivity. Building on an existing K23-funded clinical trial, this study examines parent and child stress reactivity and its role in the treatment process for pediatric OCD. Employing an integrated translational research battery, the proposed project examines parent and child stress reactivity over the course of CBT with the goal of understanding (a) how the pathophysiology of pediatric OCD changes with treatment; (b) how parent and child stress reactivity relate to ability to complete key tasks of treatment; and (c their role in treatment outcome. Stress reactivity is assessed via multiple methods, including measures of hypothalamus- pituitary-adrenal (HPA) axis reactivity (salivary cortisol) as well as established markers of sympathetic nervous system activity (salivary amylase, heart rate and skin conductance) during baseline and exposure tasks. Findings from this work have the potential to shed light on the biological underpinnings of pediatric OCD, to improve understanding of the mechanisms treatment non-response, and to guide efforts to improve interventions for refractory subgroups.

Abstract Anxiety occurs widely among adolescents, with one in three youth meeting criteria for an anxiety disorder before the age of 18. Although evidence-based treatments exist, rates of relapse are strikingly high and treatment does little to alter the chronic, fluctuating course of symptoms. To address these concerns and to achieve the mission of ?curative therapeutics? outlined in the current NIH strategic plan, factors linked to heterogeneity in the course of anxiety must be better understood. The goal of this application is to conduct a prospective longitudinal study of youth across the full continuum of anxiety symptoms, characterizing specific neural changes that underlie the evolution of illness and impairment. Existing cross-sectional research has specified a fear circuit encompassing the amygdala (AMY) and ventromedial prefrontal cortex (vmPFC) but has overlooked the role of other potentially important systems (e.g., striatum) in contributing to anxiety. Moreover, this work has failed to address multiple key questions for the field: How does identified circuitry change over time and how does this maturation relate to the course of anxiety symptoms? How do approach and avoidant processes interact and what is the role that the maturing regulatory cortex plays in modulating these limbic- based fear systems and influencing outcomes? In this study, we examine fronto-striato-limbic system development in a community sample (n=120) of youth ages 9-13, selected to exhibit the full range of anxiety symptoms with oversampling at the more severe end of the distribution. We choose this age range in light of robust evidence that it will capture significant worsening of anxiety symptom severity. Subjects will be followed annually for three years to track trajectories of change in approach/avoidance behaviors and the corresponding regulatory circuitry as well as anxiety symptom severity and related functional outcomes. We have a particular interest in tracking divergence from age-expected increases in novelty seeking and risk-taking behavior and its covariation with symptom course. At each time-point, participants will complete risky decision-making tasks while undergoing fMRI along with self-report, behavioral, and psychophysiological measures. These methods are complemented by innovative neuroimaging models that specifically test the direction of influence among target systems, which undergo substantial change in adolescence. Findings from the proposed research will shed light on the component and interactive processes by which approach-, avoidance-, and regulatory- circuitry contribute to the persistence/remittance of anxiety. The result will be a more holistic understanding of the mechanisms underlying heterogeneity in symptom course that may be used to guide the development of targeted interventions.