Altered Serotonin Function in Suicide

Abstract

Significant progress has been made in understanding psychosocial, psychological, and environmental factors associated with suicide; however, it is only recently that attention has been paid to the understanding of the neurobiology of suicide. There are several studies that implicate the serotonin (5-HT) system in suicide. Initial evidence was obtained from observations of low 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) of depressed patients with a previous history of suicide attempts. Several strategies have been used to examine the serotonergic system in suicidal behavior, which include the determination of serotonin and its metabolites in CSF and postmortem brain tissues as well as serotonin receptor subtypes in postmortem brain tissues, and in platelets of suicidal patients. The neuroendocrine strategy, often termed the "window to the brain," has been extensively used for studying the serotonergic system in suicide. This chapter will review the results obtained from neuroendocrine and serotonin studies in platelets. Initial studies in platelets focussed on determining serotonin uptake and serotonin transporter binding sites in platelets of depressed and suicidal patients. Whereas several studies have found decreased imipramine binding sites of platelets of depressed patients, imipramine binding sites in platelets of suicidal patients showed inconsistent results. Similarly, no consistent changes in 5-HT uptake have been observed in platelets obtained from suicidal patients compared to nonsuicidal patients. On the other hand, studies of platelet 5-HT2A receptors appear to be quite encouraging. Initially, several investigators indicated that they found an increase in platelet 5-HT2A receptors in depressed patients. Subsequently, it was shown that platelet 5-HT2A receptors in suicidally depressed patients were significantly higher compared to nonsuicidally depressed patients and normal control subjects. It has also been shown that platelet 5-HT2A receptors are increased in suicidal patients independent of diagnosis, similar to platelets. 5-HT2A receptors have also been shown to be increased in the postmortem brain of suicide victims by several investigators, although some investigators do not find such an increase. The neuroendocrine strategy provides an important method for studying serotonin function in the central nervous system of depressed and suicidal patents. Using a serotonergic probe of 5-HT1A receptors, several investigators examined ipsapirone-induced prolactin release in suicidal patients and did not find it different that that of control subjects. On the other hand, fenfluramine, which causes release of serotonin and blocks serotonin uptake, causes a decreased release of prolactin in depressed patients compared to normal control subjects. Furthermore it has been shown by some investigators that fenfluramine-induced prolactin release is also decreased in suicidal patients compared to normal control subjects. In summary, platelet and neuroendocrine studies have provided initial evid...

Towards a possible aetiology for depressions?

“…That tri-peptide doubled the serotonin content of platelets when injected into pups subcutaneously [ 24 ]. 5 HT 2a receptors are increased in brain tissue and platelets in depression [ 25 ] which would agree with decreased levels in the synaptic cleft due to stimulated uptake. Also the decreased 5HIAA (5-hydroxy indole-acetic acid) in suicidal patients fit an increased uptake [ 26 ].…”

Effects of Imipramine and Bupropion on the Duration of Immobility of ACTH-Treated Rats in the Forced Swim Test: Involvement of the Expression of 5-HT_2A Receptor mRNA

“…[18][19][20][21] Using drugs with significant antagonistic properties toward the 5-HT 2A receptor (mianserin and mirtazapine), in addition to selective serotonin reuptake inhibitor (SSRI)s enhanced therapeutic responses in patients with major depression. 22,23) In an animal study, a reduction in the number of 5-HT 2A receptors caused by the administration of an antisense oligonucleotide decreased the duration of immobility in the forced swim test in mice.…”

An East Meets West Approach to the Understanding of Emotion Dysregulation in Depression: From Perspective to Scientific Evidence

“…They proposed that decreased levels of 5-HT in the synaptic cleft might result in depression. A study by Pandey (1997) found that suicidal patients had lower levels of 5-HT compared to normal subjects. A study by Wägner et al.…”