Schizophrenia is one of the most devastating diseases known to humankind and is one of the top 10 causes globally of profound functional disability. Negative symptoms of schizophrenia account for much of the poor functional outcome in schizophrenia and are an unmet treatment need in a large proportion of patients. We propose to use an experimental therapeutics approach to test a novel psychosocial intervention that combines in-person and smartphone-based cognitive behavior therapy (CBT) for experiential negative symptoms in schizophrenia called, Mobile-assisted CBT for Negative symptoms (mCBTn). mCBTn is a novel extraction and integration of the CBT components that target defeatist attitudes from our cognitive behavioral social skills training (CBSST) group therapy and mobile smartphone interventions from our prior clinical trials research. The primary aim of the project is to test whether mCBTn can reduce severity of a novel treatment target: defeatist performance attitudes. In a promising new model, Beck and colleagues proposed that defeatist attitudes (e.g., Why bother, I always fail, It's not worth the effort) contribute to experientil negative symptoms like amotivation and asociality, and ultimately poor functioning in schizophrenia, because defeatist attitudes lead to avoidance of effortful goal-directed activities. Our approach centers on the hypothesis that defeatist attitudes contribute to experiential negative symptoms, including diminished motivation and effort, which ultimately leads to poor functioning in schizophrenia. In addition, the field currently relies on symptom rating scales and subjective patient reports to measure motivation and effort; more objective measures are needed. The proposed project will determine whether pupillary responses can provide an objective psychophysiological biomarker of effort that is sensitive to change in a clinical trial fr negative symptoms. Greater pupil dilation indicates greater task effort allocation. We propose two sequential clinical trials of mCBTn in consumers with schizophrenia spectrum disorders with persistent moderate-to-severe experiential negative symptoms. In the R61 phase, we propose an open trial to determine whether mCBTn changes the defeatist attitude target and will identify the optimal dose to engage the target. In the R33 phase, we propose an RCT comparing mCBTn with a supportive contact control and will determine whether mCBTn produces greater reduction in defeatist attitudes that mediates improvement in experiential negative symptoms. Pupillary responses will be recorded as a secondary outcome in both trials to determine its potential as an end point in clinical trials of motivation and effort.

Public Health Relevance

Negative symptoms of schizophrenia are an unmet treatment need in a large proportion of patients and are related to poor functioning and quality of life. The psychotherapy intervention tested in this project that uses smartphones to strengthen the intervention may reduce negative symptom severity and increase productive community contributions. From a public health standpoint, this could have significant personal, societal, and economic impact.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Special Emphasis Panel (ZMH1-ERB-D (03))
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Morris, Sarah E
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University of California San Diego
Schools of Medicine
La Jolla
United States
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