Schizophrenia is a severe and persistent psychiatric disorder that is characterized by significant impairments in cognitive function. Deficits in social cognition, or the ability to process, interpret, and regulate socio-emotional information, have been recently shown to be key rate-limiting factors to functional recovery from the illness, making them critical targets for treatment. Social-cognitive impairments reflect a presumed deficit in fronto-temporal brain function, and are unresponsive to extant pharmacologic interventions. Recently, a comprehensive cognitive rehabilitation approach known as Cognitive Enhancement Therapy (CET) has been shown to greatly improve social cognition in two NIH-supported clinical trials with schizophrenia patients. The beneficial effects of CET presumably reflect a change in underlying brain function, and when applied early in the course of illness CET may be able to capitalize on a neuroplasticity reserve to alter functional brain deficits. Indeed, we have recently shown that social-cognitive improvement in CET is associated with an enhanced structural integrity of fronto-temporal brain networks in the early course of the disorder. Beyond these initial observations, however, remarkably little is known about the neurobiologic effects of social-cognitive rehabilitation on brain function in schizophrenia. Research on the neurobiologic effects of psychosocial interventions is aligned with the NIMH priority goal of identifying neural mechanisms of psychiatric treatments, yet such studies have rarely been conducted in schizophrenia due to a lack of translational investigators trained in both intervention and neuroscience research. The purpose of this Mentored Patient-Oriented Career Development Award (K23) is to provide the applicant, a trained social worker and psychosocial interventionist, with the skills in neuroscience needed to bridge the fields of psychosocial treatment and neuroscience research in schizophrenia. The long-term goal of the applicant is to advance the treatment of schizophrenia through evaluating the effects of psychosocial interventions on the brain and developing novel psychosocial treatments to enhance brain function in the disorder. To accomplish this long-term goal, a multidisciplinary training plan has been developed to provide the applicant with complementary expertise in: (1) neuroanatomy and the neurobiology of schizophrenia; (2) social-cognitive and affective neuroscience, and (3) functional neuroimaging methods. The applicant will receive mentoring in a strong multidisciplinary environment from accomplished experts in the field of neuroscience, which will be combined with formal training and coursework designed to develop his expertise in translational neuroscience methods and approaches. A complementary research plan will conduct a cross-sectional, post-treatment outcomes study of the effects of CET on social-cognitive brain function in 32 patients in the early course of schizophrenia. This research plan will proceed by first characterizing the nature of deficits in brain function during social-cognitie processing in early course schizophrenia patients (N = 16) and matched healthy controls (N = 16) using a field standard functional neuroimaging paradigm of emotion perception, along with two novel social cognition paradigms of perspective-taking and emotion regulation. Subsequently, 16 patients in the early course of schizophrenia who have been treated with CET in a ongoing clinical service at the institution will be studied along with 16 carefully matched early course patients who have not been exposed to CET. Post-treatment functional neuroimaging data using the emotion perception, perspective-taking, and emotion regulation paradigms will be collected on both CET-exposed and CET non-exposed patients to examine the effects of the intervention on fronto-temporal brain function and connectivity. Together, these activities will support an R01 application to conduct a subsequent longitudinal randomized trial of CET effects on social-cognitive brain function, and provide the unique training and research experiences needed to enable the applicant to achieve his long-term goal of becoming an independent investigator of the effects psychosocial treatment on the brain in schizophrenia. Results from this area of investigation are expected to lead to new discoveries regarding brain plasticity in schizophrenia, identify the neural mechanisms that can support social-cognitive enhancement, and pave the way for refining existing and developing increasingly effective interventions for this highly disabling condition.

Public Health Relevance

This project proposes to conduct a post-treatment investigation of the effects of social-cognitive rehabilitation on brain function in early course schizophrenia. The information gathered from the project is of significant public health relevance, in that it will begin to provide critical information on the neural mechanisms of social cognitive enhancement in the disorder and lead to the refinement of existing and development of novel interventions to address this highly disabling aspect of schizophrenia. In addition, this project is expected to begin to elucidate the capacity of the schizophrenia brain to respond to psychosocial intervention, which will mark an important advance in the understanding of brain plasticity and the pathophysiology of the disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH095783-04
Application #
8846670
Study Section
Interventions Committee for Adult Disorders (ITVA)
Program Officer
Chavez, Mark
Project Start
2012-09-01
Project End
2016-08-31
Budget Start
2015-06-01
Budget End
2016-08-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Social Welfare/Work
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Eack, Shaun M; Hogarty, Susan S; Greenwald, Deborah P et al. (2018) Cognitive enhancement therapy for adult autism spectrum disorder: Results of an 18-month randomized clinical trial. Autism Res 11:519-530
Haigh, Sarah M; Walsh, Jennifer A; Mazefsky, Carla A et al. (2018) Processing Speed is Impaired in Adults with Autism Spectrum Disorder, and Relates to Social Communication Abilities. J Autism Dev Disord 48:2653-2662
Bishop-Fitzpatrick, Lauren; Mazefsky, Carla A; Eack, Shaun M (2018) The combined impact of social support and perceived stress on quality of life in adults with autism spectrum disorder and without intellectual disability. Autism 22:703-711
Eack, Shaun M; Wojtalik, Jessica A; Keshavan, Matcheri S et al. (2017) Social-cognitive brain function and connectivity during visual perspective-taking in autism and schizophrenia. Schizophr Res 183:102-109
Bishop-Fitzpatrick, Lauren; Mazefsky, Carla A; Eack, Shaun M et al. (2017) Correlates of Social Functioning in Autism Spectrum Disorder: The Role of Social Cognition. Res Autism Spectr Disord 35:25-34
Bishop-Fitzpatrick, Lauren; Minshew, Nancy J; Mazefsky, Carla A et al. (2017) Perception of Life as Stressful, Not Biological Response to Stress, is Associated with Greater Social Disability in Adults with Autism Spectrum Disorder. J Autism Dev Disord 47:1-16
Eack, Shaun M; Wojtalik, Jessica A; Barb, Scott M et al. (2016) Fronto-Limbic Brain Dysfunction during the Regulation of Emotion in Schizophrenia. PLoS One 11:e0149297
Eack, Shaun M; Hogarty, Susan S; Bangalore, Srihari S et al. (2016) Patterns of Substance Use During Cognitive Enhancement Therapy: An 18-Month Randomized Feasibility Study. J Dual Diagn 12:74-82
Eack, Shaun M; Newhill, Christina E; Keshavan, Matcheri S (2016) Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Early Course Schizophrenia. J Soc Social Work Res 7:211-230
Bishop-Fitzpatrick, Lauren; Mazefsky, Carla A; Minshew, Nancy J et al. (2015) The relationship between stress and social functioning in adults with autism spectrum disorder and without intellectual disability. Autism Res 8:164-73

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