Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression.

BACKGROUND Lower serotonergic activity correlates with high-lethality suicide attempts in major depression. Postmortem studies of serotonin receptors in suicides localize changes to the ventral prefrontal cortex (PFC). We studied serotonergic response in ventral PFC in depressed patients surviving a high-lethality suicide attempt. METHODS Depressed patients with a history of a high-lethality suicide attempt (n = 16) were compared with those with low-lethality attempts (n = 9) for level of depression, suicidal intent and ideation, impulsivity, aggression, and neuropsychological test performance. Subjects were scanned while medication free after a single-blind placebo and after fenfluramine hydrochloride administration on a second day. Brain responses were measured by positron emission tomography imaging of fludeoxyglucose F 18 and serial prolactin levels. Scans were compared by means of statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical and neuropsychological measures were assessed. RESULTS Depressed high-lethality suicide attempters had lower rCMRglu in ventral, medial, and lateral PFC compared with low-lethality attempters. This difference was more pronounced after fenfluramine administration. Lower ventromedial PFC activity was associated with lower lifetime impulsivity, higher suicidal intent (planning), and higher-lethality suicide attempts. Higher verbal fluency was positively correlated with rCMRglu in the same regions. CONCLUSIONS Prefrontal localized hypofunction and impaired serotonergic responsivity are proportional to the lethality of the suicide attempt and may mediate the effects of suicide intent and impulsivity on lethality. Positron emission tomographic neuroreceptor studies are needed to determine whether postmortem serotonin receptor findings are also present in vivo and contribute to the abnormal rCMRglu responses.