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

Abstract

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.

Neuroplasticity, Neurotransmission and Brain-Related Genes in Major Depression and Bipolar Disorder: Focus on Treatment Outcomes in an Asiatic Sample

“…When investigating the association with disease risk, CHL1 (rs4003413) and HTR2A (rs643627) were found to ne significantly associated with BD in case–control analysis, and with MDD as trends (other SNPs involved; see supplementary Table 2). These findings are in line with some previous evidence of the involvement of CHL1 in BD [ 49 ] and HT2A in both BD [ 50 , 51 ] and MDD [ 52 – 55 ].…”

Network science approach elucidates integrative genomic-metabolomic signature of antidepressant response and lifetime history of attempted suicide in adults with major depressive disorder

“…Kynurenine is a biogenic amine produced via tryptophan metabolism ( Peters, 1991 ) which has been separately associated with a) circadian disturbance (e.g., sleep disruption) ( Bhat et al, 2020 ), b) suicidal behavior and ideation ( Rujescu et al, 2003 ; Lin and Tsai, 2004 ; Pitchot et al, 2005 ; Lopez et al, 2007 ; Malone et al, 2007 ; Yeh et al, 2014 ; Setoyama et al, 2016 ), and c) antidepressant response ( Sun et al, 2020 ). Suicidal patients exhibit dysregulation along the tryptophan metabolism pathway at the level of enzymes (e.g., tryptophan hydroxylase I, II (TPH1, TPH2)) ( Rujescu et al, 2003 ; Lopez et al, 2007 ), receptors (5-Hydroxytryptamine Receptors 5HT1A, 5-HT2A) ( Pitchot et al, 2005 ; Malone et al, 2007 ), and transporters (serotonin transporter (5-HTTLPR)) ( Lin and Tsai, 2004 ; Yeh et al, 2014 ). Sleep deprivation activates enzymatic degradation of tryptophan along the kynurenine pathway, resulting in decreased production of melatonin and neuroprotective metabolites (e.g., kynurenic acid) and increased production of inflammatory and neurotoxic metabolites (e.g., 3-hydroxykynurenine, quinolinic acid) ( Bhat et al, 2020 ).…”

Psychological Peculiarities of Physical Rehabilitation of Patients with Ischemic Stroke

“…The multifunctionality of brain formations is manifested in the paradigm of the ability of the neurophysiological systems of the cortex and subcortex in new specific conditions to assume the functions of the loss of functional capacity of certain structures. Thus, in response to the alternative cessation of regional cerebral blood flow, the central nervous system develops as active structure and, in the most of its actions, facilitates health-generating activity (Malone, Ellis, Currier & Mann, 2006). The ability to restore functions has been lost as a result of damage to the motor cortex (locomotor acts, purposeful movements with the help of a hand (or both hands) of paralyzed people in extreme vital situations).…”