Upregulation of the Platelet Serotonin_2A Receptor and Low Blood Serotonin in Suicidal Psychiatric Patients

Abstract

Suicidality has been found to be associated with low pre- and postsynaptic serotonin functioning. The purpose of this study was to examine whether in acutely suicidal psychiatric inpatients, the blood serotonin concentration was related to the underlying psychiatric disorder and whether it was associated with changes in the affinity (dissociation constant, K_D) or in the maximal binding capacity (B_max) of the platelet serotonin_2A receptor. We therefore determined the blood serotonin concentrations and the platelet serotonin_2A receptor activities of 45 suicidal psychiatric patients and 20 healthy subjects. We found that the blood serotonin concentrations were significantly lower in suicidal patients compared to healthy subjects. In all diagnostic categories (affective disorder, schizophrenia and adjustment disorder) we noted a significantly higher maximal binding capacity of the platelet serotonin_2A receptor. These findings support the notion that a reduction in the availability of serotonin and an upregulation of the serotonin_2A receptors in psychiatric patients are associated with a loss of control over suicidal impulses.

Decreased Serotonin 5-HT2A Receptor-Stimulated Phosphoinositide Signaling in Fibroblasts from Melancholic Depressed Patients

“…For example, some studies of 5-HT 2A receptors in platelets have found significant elevations (Pandey et al, 1990(Pandey et al, , 1995Hrdina et al, 1995Hrdina et al, , 1997Rao et al, 1998;Alda and Hrdina, 2000), while others have not (McBride et al, 1994;Neuger et al, 1999;Rosel et al, 1999). Similar results have been shown in post-mortem brain specimens from depressed patients; in some studies, apparent 5-HT 2A binding was elevated (Stanley and Mann 1983;Mann et al, 1986;Hrdina et al, 1993;Arranz et al, 1994;Pandey et al, 2002a, b), but not in others (Cheetham et al, 1988;Rosel and Arranz, 1998;Gross-Isseroff et al, 1998;Rosel et al, 2000).…”

Genetics of suicide

“…108 The importance of 5-HT2A receptor upregulation as marker for suicidality was further underlined by a recent investigation showing that in suicide brains the lifetime aggression scores correlated positively with 3 H-ketanserin binding in all investigated prefrontal Brodman areas. 109 Further, several studies with platelets of suicide attempters showed an upregulation of 5-HT2A receptor as a peripheral marker for suicidality, 110,111 although a critical review claimed that methodological flaws limited the validity of platelets as biological model.…”

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

“…The direction of findings in the brain of suicides is consistent with some platelet findings in suicide attempters. For example, more platelet 5-HT 2A receptors are found in suicide attempters compared with non-attempters and healthy controls (Arora and Meltzer, 1993 ;Biegon et al, 1990 ;McBride et al, 1994 ;Pandey et al, 1990Pandey et al, , 1995Rao et al, 1998), and in individuals with suicidal ideation compared to non-suicidal psychiatric patients and controls (Alda and Hrdina, 2000 ;Bakish et al, 1997 ;Hrdina et al, 1997). Two studies observed no difference (Serres et al, 1999 ;Uchitomi et al, 2002).…”