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Updated: Aug 21, 2026

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System
Published on: April 25, 2012
PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression
Martin Reivich1, Jay D Amsterdam, David J Brunswick
1Cerebrovascular Research Center, Department of Neurology, University of Pennsylvania School of Medicine, Room 415 Stemmler Hall, Philadelphia, PA 19104-6063, USA. mreivich@mail.med.upenn.edu
Background:
Alterations in the brain serotonin (5-HT) system have been found in patients with depression. We used the selective 5-HT transporter site ligand [11C](+)McN5652 and positron emission tomography (PET) to examine the hypothesis that alterations in 5-HT transporter levels may be present in selected regions of the brain in depressed patients.
Methods:
Four drug free depressed patients and four healthy control subjects were studied using [11C](+)McN5652 and PET. The distribution volume (DV) ratio of the PET ligand in selected regions of interest (ROIs) compared to cerebellum were calculated for the ROIs.
Results:
Patients showed significantly larger DV ratios in the left frontal cortex (P=0.013) and right cingulate cortex (P=0.043) compared to control subjects.
Limitation:
The sample size was modest with gender differences between the subject groups. The PET agent, [11C](+)McN5652, may have a lower binding affinity for the 5-HT transporter in the cortical regions compared to other brain regions.
Conclusion:
These findings suggest that 5-HT transporter sites may be increased in the frontal and cingulate cortices of depressed patients. These alterations in 5-HT transporter sites may be of pathophysiologic significance in the etiology of depression and its treatment.
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