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A Positron Emission Tomography Study

Lakshmi N. Yatham, MBBS; Peter F. Liddle, PhD, MBBS; I-Shin Shiah, MD; Gayle Scarrow, BA; Raymond W. Lam, MD; Michael J. Adam, PhD; Athanasios P. Zis, MD; Thomas J. Ruth, PhD

Arch Gen Psychiatry. 2000;57:850-858.

Background  Postmortem and brain imaging studies that measured brain serotinin₂ (5-HT₂) receptors in major depression reported an increase, decrease, and no change compared with controls. In this study, we assessed brain 5-HT₂ receptors in 20 depressed patients (mean ± SD age, 40.1 ± 9.5 years; range, 22-60 years) and 20 healthy controls similar in age (37.2 ± 12.6 years; range, 19-59 years) using positron emission tomography and setoperone labeled with fluorine 18 ([¹⁸F]setoperone).

Methods  Patients with DSM-IV major depression and healthy controls underwent scanning with [¹⁸F]setoperone. All study subjects were drug free for at least 2 weeks. The 5-HT₂ binding images were created using region-to-cerebellum ratios. The differences in 5-HT₂ receptor binding potential between the two groups were determined with statistical parametric mapping software and region of interest analysis.

Results  There was a significant negative correlation between 5-HT₂ receptor binding potential and age in both patients and controls, and the magnitude of this correlation was similar in both groups. Both statistical parametric mapping and region of interest analyses showed that, compared with healthy controls, depressed patients had significantly lower 5-HT₂ receptor binding potential in frontal, temporal, parietal, and occipital cortical regions. Statistical parametric mapping analysis showed that the mean decrease in 5-HT₂ receptor binding potential for the entire cluster in these regions was 22%, and it ranged from 22% to 27% for local maxima within the clusters of significant voxels.

Conclusion  This study suggests that brain 5-HT₂ receptors are decreased in patients with major depression.

From the Division of Mood Disorders (Drs Yatham, Shiah, Lam, and Zis and Ms Scarrow), Division of Schizophrenia, Department of Psychiatry (Dr Liddle), and TRIUMF Positron Emission Tomography Program (Drs Adam and Ruth), The University of British Columbia, Vancouver; and Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (Dr Shiah).

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