Altered Serotonin Function in Suicide

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 studes that implicate the serotonin (5‐HT) system in suicide. Initial evidence awas obtainded from observations of low 5‐hydroxyin‐doleacetic 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 sub‐types in postmorte brain tissues, and in platelets of suicidal patients. The neuroendocrine strategy, often termed teh “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 studes in platelets. Initial studeis in platelets foccussed on determining serotonin uptake and serotonin trasporter binding sites in platelets of depresed and suicidal patietns. Whereas several studes 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‐HT 2A receptors appear to be quite encourageing. Initialy several investigators indicated that they found an increase in platelet 5‐HT 2A receptors in depressed patients. Subsequently, it was shown that platelet 5‐HT 2A receptors in suicidaly depressed patients were significantly higher compared to nonsuicidally depressed patients and normal control subjects. It has also been shown that platelet 5‐HT 2A receptors are increased in suicidal patients independent of diagnosis, similar to platelets. 5‐HT 2A 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‐HT 1A 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 evidence sufficient to suggest serotonergic abnormalities in suicidal patients. Most earlier evidence is based on CSF 5‐HIAA studies, but it appears that 5‐HT 2A receptors in both platelet and postmortem brain samples are increased in suicidal patients. The observation that platelet 5‐HT 2A receptors are increased in suicidal patients independent of diagnosis provides a very useful potential biological marker for identifying suicidal patients.