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Prefrontal Cortex 5-HT₂ Receptors in Depression: An [¹⁸F]Setoperone PET Imaging Study

OBJECTIVE: Widespread disturbances of serotonin (5-HT) are implicated in the pathophysiology of depression. Of 5-HT receptor abnormalities reported, the most replicated finding is increased 5-HT₂ receptor binding in the postmortem prefrontal cortex of depressed suicide victims. The extent to which these findings exist in depressed persons without recent suicide attempts is uncertain. The objective of this study was to evaluate 5-HT₂ receptors in depressed patients who were medication-free and who had not made recent suicide attempts. METHOD: With the use of [¹⁸F]setoperone and positron emission tomography (PET), 5-HT₂ receptor binding potential was assessed in 14 depressed and 19 healthy subjects. Exclusion criteria for depressed patients included use of antidepressant medication within the past 6 months, a history of suicide attempts within the past 5 years, other current axis I disorders including bipolar disorder, and the presence of psychotic symptoms. The 5-HT₂ (setoperone) binding potential in the two groups of subjects was compared by analysis of covariance with age as the covariate. RESULTS: Age had a significant effect on 5-HT₂ binding potential, but depression did not. The interaction of age and depression was not significant. CONCLUSIONS: The 5-HT₂ binding potential is not increased in untreated depressed subjects who have not made recent suicide attempts. This negative finding does not rule out the possibility that there is a role for 5-HT₂ receptors in treatment or that 5-HT₂ receptors are increased in highly suicidal states.

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