Understanding Reward Pathways in Schizophrenia

Alcohol and other substance use disorders (A/SUD) are the most common co-occurring condition in patients with schizophrenia, and problems resulting from A/SUD contribute strikingly to the overall severity of schizophrenia. Earlier studies suggest that there may be a link between how patients with schizophrenia experience rewards and A/SUD. Dysfunctional reward circuitry in the brain may itself underlie the use of substances.

Investigators at the CRC have hypothesized that clozapine (CLOZ), unlike typical antipsychotics and risperidone (collectively referred to as OTHER), may help to normalize dysfunctional brain reward circuits in these patients. To explore this hypothesis further, brain reward functioning in schizophrenic patients with comorbid A/SUD, treated with either CLOZ or other medications, were evaluated through ratings of pleasurable and aversive odors, stimuli that are processed by several brain structures thought to play a key role in processing rewarding stimuli. This NARSAD-funded study sought to expand upon recent data revealing that patients with schizophrenia rated pleasant odors as significantly less pleasurable than did controls, and that their odor-induced reward system activation was abnormal. This investigation is the first to determine whether CLOZ-treated patients within this comorbid A/SUD population are less impaired than other-treated patients, and potentially comparable to healthy controls, in subjectively evaluating pleasant odors. Findings from this study may provide important new data in support of the hypothesis that CLOZ ameliorates abnormal brain reward functioning in schizophrenic patients who abuse alcohol and other substances, and may thereby advance treatment for this dual diagnosis patient group.

We have completed recruitment for this study and are in the midst of data analyses. An intriguing finding has been emerging from the data. Preliminary results from this study suggest that CLOZ strengthens the experience of rewarding olfactory stimuli, in that the CLOZ group has been rating both pleasant and unpleasant odors more intensely (in terms of hedonic value) than either the other medication or healthy control groups; that is, they rate the pleasant odor to be more pleasant and the unpleasant odor to be more unpleasant than the other two groups! Moreover, within the other group, average hedonic ratings have been similar between the neutral and pleasant odors. These preliminary findings are compatible with the study hypotheses and suggest that CLOZ seems to strengthen the hedonic experience of rewarding stimuli, both of a pleasant and unpleasant nature. Further, more detailed, results should be available in the near future.

To receive more information about this study, contact the Principal Investigator:

Dr. Raquelle Mesholam-Gately:
Phone: 617-626-9409