Motivational Negative Symptoms in Schizophrenia: Intervention and Biomarkers

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 DESCRIPTION: Negative symptoms significantly interfere with daily functioning and contribute to the poor community outcomes of Veterans with schizophrenia. There are two main types of negative symptoms: expressive (flat affect, alogia) and motivational (avolition and asociality). It is the motivational negative symptoms that interfere with obtaining and maintaining employment [1], forming social relationships [2] and living independently [3]. Negative symptoms in schizophrenia are considered an unmet treatment need. They also offer us a treatment target that would vastly improve the daily lives of many Veterans with SCZ. Treatment development is a primary goal of the current proposal, as is the examination of potential neurophysiological biomarkers of motivation. Biomarkers for motivational negative symptoms can be used as sensitive endpoints in clinical trials and can help us understand the causes and treatments of motivational negative symptoms. The current CDA proposal will assess the feasibility of a treatment for motivational negative symptoms adapted from established motivational enhancement (MI) techniques and augmented with cognitive-behavioral approaches, in a randomized controlled trial. I will assess the efficacy of MI with measures from multiple outcome domains: 1) clinically-rated motivational negative symptoms; 2) functional outcomes (real-world improvements in social, instrumental, and independent living); and 3) neurophysiological biomarkers (pupillometry and electroencephalography (EEG)). Veterans will be randomly assigned to the MI treatment or a control treatment for weekly 1-hour sessions for 12 weeks. The assessment battery will be administered at baseline, at completion of treatment, and at 3-month follow-up. We will enroll 100 Veterans with schizophrenia and high motivational negative symptoms across the 4 years of the study. This proposal is designed to examine group-based MI for reducing motivational negative symptoms and investigating biomarkers of motivation with pupillometry and EEG. It is expected that this recovery-oriented group MI treatment for Veterans with disabling motivational negative symptoms will yield results to inform larger treatment trials and enhance neurophysiological measurement of motivational negative symptoms in Veterans with schizophrenia.