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Increased 5-HT_2A Receptor Binding in Euthymic, Medication-Free Patients Recovered From Depression: A Positron Emission Study With [¹¹C]MDL 100,907

OBJECTIVE: A previous positron emission tomography (PET) study reported increased serotonin 5-HT_2A receptor binding in unmedicated depressed patients with high scores on the Dysfunctional Attitudes Scale. The purpose of the present study was to use the highly selective 5-HT_2A receptor ligand [¹¹C]MDL 100,907 in a PET imaging paradigm to assess 1) 5-HT_2A receptor binding potential in euthymic subjects with a history of recurrent depression and 2) the relationship between receptor binding and scores on the Dysfunctional Attitudes Scale. METHOD: Cortical 5-HT_2A receptor binding was measured in 20 unmedicated, fully recovered unipolar depressed patients and 20 age- and gender-matched comparison subjects. Regional estimates of binding potential were obtained using a reversible plasma input function compartmental model and the cerebellum as a reference region to estimate the free and non-specifically bound [¹¹C]MDL 100,907 in brain tissue. RESULTS: Relative to the comparison subjects, the recovered depressed patients demonstrated significantly higher 5-HT_2A receptor binding potential in the frontal cortex (mean increase: 19%), parietal cortex (mean increase: 25%), and occipital cortex (mean increase: 19%). 5-HT_2A receptor binding potential correlated negatively with age in both patients and comparison subjects and positively with the Dysfunctional Attitudes Scale in the recovered patients. CONCLUSIONS: These findings should be considered preliminary but suggest that recovered subjects with a history of recurrent major depression have elevated binding potential of cortical 5-HT_2A receptors. The correlation of increased 5-HT_2A receptor binding potential with increased scores on Dysfunctional Attitudes Scale supports earlier work suggesting that increased 5-HT_2A receptor availability characterizes a group of depressed patients with high levels of dysfunctional attitudes.

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