Motivational Negative Symptoms in Schizophrenia: Intervention and Biomarkers

Despite significant advances in pharmacological treatments for schizophrenia (SCZ), the rate of disability among Veterans diagnosed with SCZ remains high. Functional disability among Veterans with SCZ creates a huge and costly burden on the national VA healthcare system, and interferes with community integration and quality of life. In particular, SCZ is associated with low rates of employment, few social relationships, and poor independent living skills. The negative symptoms of SCZ (i.e. avolition, anhedonia, asociality) are primary determinants of functional impairments, and they have no validated treatments. Extensive work has been devoted to treating positive symptoms and cognitive deficits, but much less has been done to develop pharmacological and psychosocial treatments for negative symptoms. Developing such interventions is a critical public health goal, as it would benefit one of the largest groups of disabled Veterans. The recently-emerging recovery-oriented approach to serious mental illness reflects a fundamental shift from a focus on symptom reduction to a focus on patients' goals and community functioning. Developing treatments for negative symptoms to augment community functioning is a strong reflection of this shift. Importantly, preliminary research suggests that motivational negative symptoms respond to novel evidence-based psychosocial interventions. The primary goal of this proposal is to adapt and implement a recovery-oriented evidence-based intervention, Motivational Interviewing (MI), for the treatment of motivational negative symptoms in Veterans with SCZ. MI, originally developed for substance use disorders, is effective to increase commitment to new behaviors in a range of areas including treatment adherence, exercise, gambling, and depression. Importantly, it has been shown to be applicable to Veterans with psychosis, but it is not known if MI can reduce functional deficits that are attributable to motivational negative symptoms. More specifically, the scientific goals of this proposal are to: 1) evaluate the efficacy of a group-based MI intervention on motivational negative symptoms for Veterans with SCZ, and 2) to examine potential biomarkers of negative symptoms and treatment response. I will assess the efficacy of MI with measures from two outcome domains: 1) negative symptoms (clinical ratings) and 2) functional outcomes (real-world improvements in social, instrumental, and independent living). I will assess the relationship between these outcomes and neurophysiological biomarkers (pupillometry and electroencephalography (EEG)). To address these questions, 60 Veterans with SCZ who have at least moderate levels of motivational negative symptoms will be randomly assigned in a 1:1 ratio to MI or a standard treatment (relaxation skills training). Both treatments will consist of weekly 60-min group sessions for twelve weeks. The assessment will be administered at baseline, at completion of treatment, and at 6-month follow-up. Specific Aim #1: To adapt the existing MI approach for group-based MI treatment for Veterans with SCZ. Specific Aim #2: To examine the treatment effects of MI compared to the control procedure on motivational negative symptoms and functional outcomes. Hypothesis 2a: Individuals who receive MI will have significant improvements in motivational negative symptoms, compared to those who receive the control. Hypothesis 2b: Individuals who receive MI will have significant improvements in aspects of functioning including social, instrumental, and independent living domains, compared to those who receive the control. Specific Aim #3: To examine neurophysiological biomarkers (i.e., EEG and pupillometry) of motivational negative symptom severity and treatment response. Hypothesis 3a: At baseline, subjects with more negative symptoms at baseline will have more aberrant EEG and pupillary measures. Hypothesis 3b: For subjects in the treatment group, change in the biomarkers (toward normalization) over study duration will correlate with treatment related improvement in motivational negative symptoms. Exploratory Aim: To explore a causal model by examining whether MI improves defeatist beliefs compared to a control procedure. Although MI is a well-established intervention for a range of clinical populations and conditions, the proposed project will be the first examination of MI in a group format for motivational negative symptoms in SCZ. If validated, it could be disseminated throughout the VA for other patient populations with motivational and functional deficits (e.g., traumatic brain injury, post-traumatic stress disorder). Therefore, this CDA application will facilitate my research independence and provide me with a unique combination of skills that will equip me to be a local professional resource and long-term VA researcher.