The International Journal of Neuropsychopharmacology

Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in depressed in-patients

Kevin M. Malone a1, Steven P. Ellis a1a2, Dianne Currier a1 and J. John Mann a1a2c1
a1 Department of Psychiatry, Columbia University, New York, NY, USA
a2 Division of Neuroscience, New York State Psychiatric Institute, New York, NY, USA

Article author query
malone km   [PubMed][Google Scholar] 
ellis sp   [PubMed][Google Scholar] 
currier d   [PubMed][Google Scholar] 
john mann j   [PubMed][Google Scholar] 


In depressed patients, high-lethality suicidal acts are accompanied by serotonin system abnormalities analogous to those seen in completed suicides. We have previously reported greater platelet 5-HT2A receptor density, and impaired serotonin enhancement of ADP-induced platelet aggregation, an indirect measure of signal transduction, in high-lethality suicide attempters. We hypothesized that serotonin-activated phosphoinositide (PI) hydrolysis, a direct measure of platelet serotonin 5-HT2A receptor responsivity would be lower in depressed high-lethality suicide attempters. Twenty-three depressed in-patients that had previously made suicide attempts (low-lethality, n=6; high-lethality, n=17) had platelet 5-HT2A-mediated serotonin-simulated PI hydrolysis assayed. Platelet 5-HT2A receptor responsivity in high-lethality suicide attempters was 41% that of low-lethality suicide attempters (p<0.05). A seasonal effect was also observed. High-lethality suicidal acts are associated with more 5-HT2A receptors but impaired signal transduction.

(Received November 18 2005)
(Reviewed January 19 2006)
(Revised April 12 2006)
(Accepted May 13 2006)
(Published Online August 8 2006)

Key Words: Attempted; depression; 5-HT2A receptor; suicide.

c1 Division of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA. Tel.: (212) 543-5571 Fax: (212) 543-6017 E-mail: