Cognitive impairment associated with schizophrenia (CIAS) is a major focus of treatment research because it is acknowledged as a core feature of the syndrome that is more reliably associated with functional outcomes than traditionally rated symptoms. Despite its centrality to current concepts of pathophysiology and treatment, there are no accepted clinical rating scales for CIAS. The proposed research will develop and assess reliability and validity of a new scale: Clinical Ratings of Neurocognition (CRON). CRON will provide: (1) face-valid measures of severity and change of cognitive dysfunction that will likely be needed for regulatory approval of agents targeting CIAS; (2) important information about real-world cognitive functioning and its relations to activities of daily living, complementing standardized cognitive tests; and (3) a new tool for clinicians that will enhance their sensitivity to cognitive deficits in schizophrenia, and increase their attention to features of the illness more relevant to long-term outcome and functional disability. Clinicians using CRON will base their ratings on interviews of patients and caregivers, sampling the seven domains of neurocognitive impairment important for schizophrenia treatment research as determined by the NIMH- MATRICS consensus process. Modern psychometric methods will be used to maximize CRON's sensitivity to cognitive impairment and change over the range most likely to be targeted in treatment trials. Phase 1 of the proposed research develops a beta version of CRON, using Classical Test Theory and Item Response Theory methods to refine an over-inclusive item-bank derived from assessments completed in 210 people with schizophrenia using first-generation instruments, the Clinical Global Impression of Cognition in Schizophrenia from UCLA, and the Schizophrenia Cognition Rating Scale from Duke. Phase 2 will deploy CRON in an independent study of 288 participants, to provide more detailed assessment of psychometric properties, preliminary evidence of inter-rater and test-retest reliability, and concurrent and discriminant validity with respect to standardized tests of neurocognitive function, proxy measures of functional capacity, measures of community function, and symptoms measured with traditional rating scales. The proposed developments are urgently needed to continue the momentum established by the MATRICS initiative, and facilitate regulatory acceptance and clinical awareness of new treatments for CIAS. ? ? ?
