Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in depressed in-patients.
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.
Malone
Kevin M
KM
Department of Psychiatry, Columbia University, New York, NY, USA.
Ellis
Steven P
SP
Currier
Dianne
D
John Mann
J
J
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000523:psychology; D001792:Blood Platelets / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D003865:Major Depressive Disorder / Q000097:blood* / Q000523:psychology*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007297:Inpatients; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010716:Phosphatidylinositols / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000097:blood*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D012621:Seasons; D015290:Second Messenger Systems / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000523:psychology*
D000316:Adrenergic alpha-Agonists; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D018341:Receptors, Adrenergic, alpha-2; D004837:Epinephrine