Increased 5HT2A Receptors and Impaired Phosphoinositide Signaling in the Postmortem Brain of Suicide Victims

Abstract

Abnormalities in the serotonergic system have been implicated in suicidal behavior; however, the neurobiology of teenage suicide is relatively unexplored. We have studied 5HT2A receptors, phospholipase C (PLC), and protein kinase C (PKC), which are important components of the phosphoinositide (PI) signaling system and to which 5HT2A receptors are linked, in the postmortem brain of teenage suicide victims and nonpsychiatric controls. We found that the number of binding sites (Bmax) for the 5HT2A receptor were increased without any change in the affinity in the membrane fraction and that [3H]PDBu binding to PKC was decreased in the membrane and cytosol fractions of prefrontal cortex of teenage suicide victims as compared to nonpsychiatric control subjects. We also found that the mean PI-PLC activity was significantly decreased in both the membranal and cytosolic fractions of the prefrontal cortex of teenage suicide victims as compared to nonpsychiatric control subjects, and this decrease was accompanied with selective decrease in the immunolabeling of PLC β1 isozyme without any significant change in PLC-δ1 or PLC-γ1 These studies thus indicate that the 5HT2A receptors, PKC, and PLC are altered in teenage suicides such that the phosphoinositide signaling system to which 5HT2A receptors are linked appear to be impaired in these individuals.