Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge and Lethality of Suicide Attempts in Major Depression

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Abstract
SUICIDE ATTEMPTERS have decreased serotonergic function compared with psychiatric control subjects as measured by prolactin response to fenfluramine hydrochloride1,2 and lower cerebrospinal fluid levels of 5-hydroxyindoleacetic acid.3,4 Higher-lethality suicide attempts in depressed subjects are associated with even lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels5 and a more blunted prolactin response to fenfluramine.1 Postmortem serotonin receptor binding mapping studies indicate that cortical serotonergic abnormalities associated with suicide are localized to the ventral prefrontal cortex (PFC).6 Neuroendocrine challenges and cerebrospinal fluid measures do not provide information about the anatomic location of abnormality. We did not find any studies of glucose metabolism in response to fenfluramine and suicidal behavior with the use of positron emission tomography (PET). However, changes in glucose metabolism in the PFC have been reported in impulsive murderers compared with nonimpulsive murderers,7 impulsive aggressive subjects compared with normal controls,8 and subjects with borderline personality disorder compared with healthy volunteers. Typically in these studies either there is a large proportion of suicide attempters9 or the attempter status of the subjects is not described.7,8 Therefore, we studied regional brain serotonergic function in depressed patients with a history of a high-lethality suicide attempt compared with that of depressed patients with a history of low-lethality suicide attempt by PET of relative regional cerebral uptake of fludeoxyglucose F 18 (18F) (rCMRglu) in response to serotonin elevation after a fenfluramine challenge relative to a placebo challenge.