PROJECT SUMMARY/ABSTRACT
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. Eighty 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.