Neural mechanisms of anhedonia in schizophrenia: a PET study of response to unpleasant and pleasant odors.

CONTEXT Loss of the capacity to experience pleasure (anhedonia) is a core clinical feature of schizophrenia. Although functional imaging techniques have been successful in identifying the neural basis of cognitive impairments in schizophrenia, no attempts to date have been made to investigate neural systems underlying emotional disturbances. OBJECTIVE To study the neural basis of emotional processing in schizophrenia by exploring the pattern of brain responses to olfactory stimuli in patients and healthy volunteers. DESIGN Positron emission tomographic study of patients with schizophrenia and healthy volunteers. Positron emission tomographic data were collected between July 21, 1995, and September 11, 1997, and data analyses were conducted in 1999-2001. SETTING The Mental Health Clinical Research Center at the University of Iowa, Iowa City. PARTICIPANTS Sixteen healthy volunteers with a mean age of 29.5 years and 18 patients with schizophrenia and a mean age of 30.0 years. MAIN OUTCOME MEASURE Areas of relative increase or decrease in regional cerebral blood flow, measured using positron emission tomography and the [(15)O]water method while participants performed an emotion-induction olfactory task to determine response to pleasant (vanillin) and unpleasant (4-methylvaleric acid) odors, compared between patients and healthy volunteers. RESULTS Patients with schizophrenia subjectively experienced unpleasant odors in a manner similar to healthy volunteers but showed impairment in the experience of pleasant odors. The analysis of the regional cerebral blood flow revealed that patients failed to activate limbic/paralimbic regions (eg, insular cortex, nucleus accumbens, and parahippocampal gyrus) during the experience of unpleasant odors, recruiting a compensatory set of frontal cortical regions instead. CONCLUSION Abnormalities in the complex functional interactions between mesolimbic and frontal regions may underlie emotional disturbances in schizophrenia.