The earliest signs of schizophrenia and other psychotic disorders typically emerge during adolescence and early adulthood. Yet we know little about how to intervene during this critical period to avert the onset of illness and associated disability. An NIMH priority, now with heightened public support, is to have well trained investigators capable of developing new interventions for these youth at clinical high risk (CHR). Their task is to develop tools to better define risk and protective factors for mental illness and o develop interventions targeting the most robust and malleable factors. Altering the trajectory of major mental illness through targeted intervention for CHR youth will have high public health impact, reducing suffering, burden, and expense. The proposed integrated training and research project entitled, """"""""Innovative intervention for reducing stress reactivity and risk for psychosis"""""""" i designed to prepare the candidate, Dr. Kristen Woodberry, to be one of these researchers. A Harvard-trained research psychologist in the Commonwealth Research Center (CRC) at Beth Israel Deaconess Medical Center (BIDMC) and Instructor in Psychology at Harvard Medical School (HMS), she has directed studies of CHR youth for the past 3.5 years, developing a rich community referral network. She has over 17 years of clinical experience with CHR youth and their families, experience designing and managing clinical trials, and eight first author publications, including one that has become a classic. Thus, Dr. Woodberry is well positioned to become an investigator of new interventions for this high priority population. Her long-term career goal is to test psychosocial mechanisms for reducing risk and enhancing protective factors for CHR youth. Her specific interest is in developmentally informed interventions that harness the protective function of the family and enhance resilience to stress. To pursue this line of research, Dr. Woodberry needs the statistical skills for analyzing complex longitudinal data, expertise in the science and strategies for reducing stress reactivity, and advanced training in clinical trial design and grant-writing. The proposed training will be facilitated by a truly world-class team of mentors and include formal courses, workshops, directed study and mentored research corresponding to three major training goals. These are to 1) develop expertise in longitudinal and multilevel data analysis to test models of change over time, 2) enhance her grasp of the science of stress reactivity and strategies for reducing it, and 3) obtain advanced training in clinical trial design and grant-writing to secure research funding as an independent clinical investigator. Two of the potential mechanisms for interrupting the link between stress and psychosis are to 1) improve interpersonal effectiveness (reducing interpersonal conflict and improving social support) and 2) improving executive control of emotion (reducing stress reactivity through emotion regulation). The proposed research builds on evidence from developmental psychopathology research, physiological studies of schizophrenia and adolescents at familial high risk for schizophrenia, and the science of social cognition and emotion regulation. Its primary aim is to establish the feasibility of a novel multiuser biofeedback game intervention using """"""""Emotional Manipulatives"""""""" with CHR youth and family members. Measures of enrollment, engagement, credibility, satisfaction, and the direction and standard deviation of effects will be collected to achieve this aim. Its secondary aim is to conduct preliminary analyses of relationships between changes in stress, interpersonal experience, and symptoms to further develop the underlying model and intervention design. Importantly, in addition to measures of ANS arousal during rest and during the course of the Emotional Manipulatives, measures of stress, affect, and symptom data from daily life and measures of physiological reactivity in the context of a stressful family interaction will be collected. These longitudinal and multilevel data will not only provide opportunity to examine the relationship of successful arousal reduction during the intervention to reduction of affective and physiological reactivity in real-life contexts, they will provide opportunity for mentored practiceof new statistical methods integrating and exploring the interaction of physiological, behavioral, psychological, and environmental processes. This feasibility trial of 34 CHR youth ages 13-23 and their parents will yield new knowledge related to the malleability and relevance of stress reactivity in CHR youth and facilitate training in research methods and clinical trials. Dr. Woodberry's primary mentor, Dr. Larry Seidman, is a renowned schizophrenia researcher with substantial funding success and experience mentoring early career scientists. Dr. Woodberry's successful transition to independence will be supported by the enriched academic environment and resources of the CRC, BIDMC, Massachusetts Mental Health Center, and HMS/Longwood Medical Area. These include the infrastructure of the Psychosis Research Program led by Drs. Larry Seidman and Matcheri Keshavan, exemplary academic training, including training and support specific to K Awardees, and collaborators at nearby Boston Children's Hospital, the developers of the Emotional Manipulatives adapted for use with this new population. In summary, this project combines the talent of an outstanding early investigator, a superb scientific environment with relevant resources, a world-class team of mentors and a highly innovative, theory- driven line of research in an area of high priority for NIMH and for public health. This combination of talent and resources hold high promise for making a meaningful contribution to the prevention of psychosis.

Public Health Relevance

The urgent need for new approaches to engage and treat youth with emerging mental illness has been highlighted by tragic events covered by the media. To address this major public health concern, the candidate's career development proposal would prepare her to develop and test new strategies for preventing the full expression of psychosis and the disability that so often accompanies it. The specific project proposed will explore whether a new intervention integrating videogames, biofeedback, and family involvement can 1) engage young people in the earliest stages of mental illness in strategies that build resilience and strengthen natural supports, and 2) shed light on how stress reactivity contributes to the emergence of psychosis.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Interventions Committee for Disorders Involving Children and Their Families (ITVC)
Program Officer
Sarampote, Christopher S
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Beth Israel Deaconess Medical Center
United States
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Kline, Emily R; Chokran, Cole; Rodenhiser-Hill, Janine et al. (2018) Psychosis screening practices in schools: A survey of school-based mental health providers. Early Interv Psychiatry :
Friedman-Yakoobian, Michelle S; West, Michelle L; Woodberry, Kristen A et al. (2018) Development of a Boston Treatment Program for Youth at Clinical High Risk for Psychosis: Center for Early Detection, Assessment, and Response to Risk (CEDAR). Harv Rev Psychiatry 26:274-286
Woodberry, Kristen A; Seidman, Larry J; Bryant, Caitlin et al. (2018) Treatment Precedes Positive Symptoms in North American Adolescent and Young Adult Clinical High Risk Cohort. J Clin Child Adolesc Psychol 47:69-78
Li, Huijun; Zhang, TianHong; Xu, LiHua et al. (2017) A comparison of conversion rates, clinical profiles and predictors of outcomes in two independent samples of individuals at clinical high risk for psychosis in China. Schizophr Res :
Thermenos, Heidi W; Juelich, Richard J; DiChiara, Samantha R et al. (2016) Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis. Schizophr Res 173:1-12
Stone, William S; Mesholam-Gately, Raquelle I; Giuliano, Anthony J et al. (2016) Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers. Schizophr Res 172:106-13
Woodberry, Kristen A; Shapiro, Daniel I; Bryant, Caitlin et al. (2016) Progress and Future Directions in Research on the Psychosis Prodrome: A Review for Clinicians. Harv Rev Psychiatry 24:87-103
Gonzalez-Heydrich, Joseph; Enlow, Michelle Bosquet; D'Angelo, Eugene et al. (2016) N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth. Neural Plast 2016:4209831
Zhang, TianHong; Li, HuiJun; Woodberry, Kristen A et al. (2015) Interaction of social role functioning and coping in people with recent-onset attenuated psychotic symptoms: a case study of three Chinese women at clinical high risk for psychosis. Neuropsychiatr Dis Treat 11:1647-54
Zhang, TianHong; Li, HuiJun; Stone, William S et al. (2015) Neuropsychological Impairment in Prodromal, First-Episode, and Chronic Psychosis: Assessing RBANS Performance. PLoS One 10:e0125784

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