Schizophrenia and co-occurring substance use disorder: reward, olfaction and clozapine

Co-occurring substance use disorders (SUD), including alcohol, are common in schizophrenia (SZ) and are associated with poor outcome. Emerging data suggest that individuals with SZ have a dysfunctional brain reward circuit that may underlie their frequent use of alcohol and other substances, and further, that the atypical antipsychotic, clozapine (CLOZ), limits alcohol/substance use in these individuals, potentially by ameliorating this brain reward circuit dysfunction. To explore this hypothesis, reward functioning in a SZ sample with a history of co-occurring SUD, treated with either CLOZ (n=13) or typical antipsychotic agents (TYP), haloperidol or fluphenazine (n=14), as well as healthy controls (n=16), was evaluated through ratings of pleasurable and aversive odors, stimuli that are processed by several neural structures thought to play a key role in processing rewarding stimuli. Results suggest that CLOZ treatment is associated with broadening and strengthening the hedonic experience of these rewarding olfactory stimuli, both of a pleasant and unpleasant nature. This hedonic appraisal of odors appeared to be independent of odor perception (intensity ratings) and clinical symptoms. These preliminary findings provide important new data in support of the hypothesis that CLOZ ameliorates some aspects of abnormal brain reward functioning in individuals with co-occurring SZ and SUD. Further research may have valuable treatment implications for this population including interventions for other reward-associated deficits in learning, social interactions and other aspects of behavior and cognition.