Neural Mechanisms of Anhedonia in Schizophrenia

A PET Study of Response to Unpleasant and Pleasant Odors

Crespo-Facorro, Benedicto MD, PhD
Paradiso, Sergio MD, PhD
Andreasen, Nancy C. MD, PhD
O'Leary, Daniel S. PhD
Watkins, G. Leonard PhD
Ponto, Laura L. B. PhD
Hichwa, Richard D. PhD

Author Affiliations: Mental Health Clinical Research Center, Department of Psychiatry, College of Medicine, University of Iowa Hospitals and Clinics, Iowa City (Drs Crespo-Facorro, Andreasen, and O'Leary); Hospital Universitario Marques de Valdecilla, Santander, Spain (Dr Crespo-Facorro); University of Iowa, Department of Psychiatry (Dr Paradiso), and The Positron Emission Tomography Imaging Center, University of Iowa Hospitals and Clinics, Department of Radiology (Drs O'Leary, Watkins, Ponto, and Hichwa), Iowa City.

Corresponding Author and Reprints: Nancy C. Andreasen, MD, PhD, University of Iowa Hospitals and Clinics, Mental Health Clinical Research Center, Room 2911 JPP, 200 Hawkins Dr, Iowa City, IA 52242-1057 (e-mail: [email protected]).

JAMA: The Journal of the American Medical Association 286(4):p 427-435, July 25, 2001.

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 [¹⁵O]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.

JAMA.2001;286:427-435