title: Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression.
abstract: 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.
authors.affiliation: Department of Psychiatry, Columbia University, New York, USA. mao4@columbia.edu
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.forename: Giovanni P A
authors.initials: GP
authors.lastname: Placidi
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Malone
authors.forename: Carl
authors.initials: C
authors.lastname: Campbell
authors.forename: John
authors.initials: J
authors.lastname: Keilp
authors.forename: Beth
authors.initials: B
authors.lastname: Brodsky
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Cooper
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.forename: Ronald L
authors.initials: RL
authors.lastname: van Heertum
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D000328:Adult; D000367:Age Factors; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007175:Impulsive Behavior / Q000378:metabolism / Q000523:psychology; D008297:Male; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012701:Serotonin / Q000378:metabolism* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013406:Suicide, Attempted / Q000523:psychology* / Q000706:statistics & numerical data; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D005277:Fenfluramine; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D006897:Hydroxyindoleacetic Acid; D011388:Prolactin; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors