Functional Significance of Structural Brain Change During Cognitive Remediation in Early Schizophrenia

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7. PROJECT SUMMARY/ABSTRACT Schizophrenia is characterized by severe functional disability, which places great burden on patients, their caregivers, and society. The available treatments for schizophrenia have not been overwhelmingly successful at reestablishing prior functional abilities. Cognitive remediation treatments display considerable promise for addressing poor functional outcome, but optimization of treatment protocols is impeded by a lack of knowledge of active neural mechanisms that can support improved functional recovery. Progressive loss of fronto-limbic gray matter is one of the most commonly replicated findings in schizophrenia, and is significantly predictive of long-term outcome. Cognitive remediation may achieve its effects, in part, by protecting against gray matter loss (or increasing gray matter) in early course schizophrenia, which can be targeted to improve functional recovery. An NIMH priority is to research the neurobiological effects of psychosocial treatments that will identify neural treatment targets and mechanistic pathways of improvement. Unfortunately, such studies are rare because translational investigators who can connect treatment, brain, and functional outcome data are exceedingly rare. Therefore, the purpose of this Predoctoral Individual National Research Service Award (F31) is to provide the applicant, a trained clinical social worker, with unique training in foundational cognitive neuroscience research and longitudinal neuroimaging data analysis. The training plan is considerably focused on providing the applicant with needed hands-on experience in the practical elements of conducting a neuroimaging study (e.g., data collection and generation) and the analysis of neuroimaging data within a clinical trial. Training and research goals will take place in the context of an ongoing NIMH-funded multi-site randomized-controlled trial of Cognitive Enhancement Therapy (CET; Brain Imaging, Cognitive Enhancement and Early Schizophrenia; R01 MH-92440; Keshavan and Eack, PIs; N = 86). The novel research plan proposed will examine the functional significance of fronto-limbic brain alterations associated with CET vs. an enriched supportive comparison therapy in early-course schizophrenia. Specific aims of the proposed research plan that will provide an excellent and unique training opportunity for the applicant are to (1) replicate the effectiveness of CET on functional outcome, (2) examine the structural neural correlates of improved functioning, and (3) identify structural neural mechanistic pathways toward improved functioning associated with CET. Together, these activities will support the applicant’s long-term career goal to become an independent researcher concentrated on advancing the treatment of schizophrenia by developing, refining, and testing neuroscience-informed interventions to enhance functional recovery. It is expected that this research will lead to new discoveries around neural targets and treatment biomarkers that will help refine cognitive remediation interventions. Findings from this research also have important implications for the understanding of brain dysfunction and plasticity in schizophrenia and their contribution to functional recovery.