FUNCTIONAL SIGNIFICANCE OF GRAY MATTER PLASTICITY FOLLOWING COGNITIVE ENHANCEMENT IN EARLY SCHIZOPHRENIA

This dissertation conducted the first examination of the degree to which changes in gray matter volume during a social work-developed cognitive remediation intervention, Cognitive Enhancement Therapy (CET), mediated improved functional outcomes in the early course of schizophrenia. Schizophrenia is a severe, chronic, and neurobiological-based mental health condition characterized by considerable functional disability. Cognitive remediation has displayed promise for addressing poor functional outcomes in the condition. Despite evidence of the neuroplastic effects of cognitive remediation, connections have yet to be made between brain and functional outcome changes during treatment. This information is vital for refining treatments to target the neural systems that have the strongest effect on functioning. Data for this research came from an NIMH-funded multi-site clinical trial investigating the neurobiological effects of CET in early course schizophrenia (R01 MH-92440). A total of 106 early course schizophrenia outpatients were randomized to either 18 months of CET (n = 61) or an Enriched Supportive Therapy (EST; n = 45). Participants completed functioning measures and MRI scans at baseline, 9, and 18 months. Intent-to-treat linear mixed-effects models were used to investigate differential change trajectories in functioning and gray matter volume between CET and EST. Mediation models examined the indirect effect of CET-related gray matter volume changes on the relationship between treatment assignment and functional outcome changes. Results indicated that CET had a significant beneficial impact on functional performance and social functioning relative to EST. A significant neuroprotective effect of CET was observed on an accelerated rate of increasing left posterior cingulate cortex (PCC) gray matter volume, relative to an accelerated decline in EST. Significant longitudinal relationships were observed between accelerated left PCC gray matter volume increases and accelerated improvements in functional performance and social functioning across the entire sample. Differential effects between CET and EST on social functioning were partially mediated by CET-related accelerated increases in left PCC gray matter volume. These results establish a new understanding of how cognitive remediation-related brain changes contribute to meaningful changes in functioning, which has important implications for improving the effectiveness of cognitive remediation, in addition to social work practice and the larger mental health field