What the Nose Knows: Hedonic Capacity, Psychosocial Interventions and Outcomes in Schizophrenia - Modified Project Summary/Abstract Section While psychotic symptoms are the most florid manifestations of schizophrenia, impairments in social and cognitive functioning are the most disabling features, and represent critical targets for intervention. Cognitive Enhancement Therapy (CET) and Social Skills Training (SST) are established, evidence-based psychosocial interventions that target functional disability in schizophrenia, but outcomes can be heterogeneous. The potential important contribution of the brain’s reward system functioning to the heterogeneity of these effects has yet to be examined. The role of reward circuitry in the cognitive, emotional and behavioral deficits of schizophrenia has garnered increasing attention in recent years, particularly given the critical relationship of reward to learning and social interactions, and the substantial public health importance of its potential association with better functional outcomes. While there are several measures of reward processes, a growing number of studies have used the olfactory system to characterize the neural substrate of the reward system and probe hedonic capacity across the psychosis spectrum. This includes preliminary findings, in people with schizophrenia, that olfactory hedonic capacity (OHC; range of hedonic ratings between pleasant and unpleasant odors) is reduced, though not in those treated with clozapine, and that OHC moderates neurocognitive outcomes in a CET clinical trial. Additionally, these olfactory assessments have the advantages of low test burden in terms of time, tolerability, cost and ease of administration, along with strong reliability and less susceptibility to state-dependent variation than questionnaires and some behavioral indices. As such, to address heterogeneous treatment effects and strive to improve outcomes, this novel project proposes the first investigation of OHC as a moderator of CET and SST effectiveness with special attention to the relationship to other indices of reward and to the role of medication. One hundred-sixteen adults with schizophrenia will be recruited from a large, 19-site, randomized clinical trial of CET vs. SST in schizophrenia, with comparable enrollment between the treatments, and assessments at baseline, 6, and 12 months (end of intervention). Moderator analyses will evaluate the predictive effects of OHC on CET and SST outcomes of community functioning, neuro- and social cognition, and social skills. The relationship between OHC and other indices of reward and clinical symptoms will also be analyzed, as will the potential interaction between medication (clozapine vs. other) and OHC on outcomes. The preliminary data from this project are expected to inform a highly promising line of research that is critical for advancing the treatment of functional impairment in schizophrenia. In examining the predictive utility of OHC measurement for targeted psychosocial rehabilitation, this projects aligns with: a). R21 guidelines emphasizing novelty and innovation, b). RDoC principles of providing mechanistic knowledge about which individuals are most likely to benefit from these interventions, and c). NIMH strategic objectives to facilitate the tailoring of existing interventions and development of new approaches to optimize outcomes for people with schizophrenia.
