5-Hydroxytryptamine in the Hind-Brain of Depressive Suicides

Abstract

There is growing evidence of a connection between the metabolism of monoamines and severe depressive illness, but the exact role of these substances in affective disorders has yet to be defined. We know that reserpine depletes the brain of monoamines and that a proportion of patients treated with this compound develop a depressive illness. Conversely a number of compounds which raise the levels of amines in the brain by blocking the enzyme monoamine oxidase have been used in antidepressant therapy. The knowledge that loss of amines may be associated with depression, and that their replenishment in the brain may induce recovery, immediately leads to the question as to which of the biogenic amines is responsible for the affective changes. Pollin, Cardon and Kety (1961) observed the effect of giving various amino acids together with a monoamine oxidase inhibitor (M.A.O.I.) to patients suffering from chronic schizophrenia. They found that only tryptophan, the precursor of the monoamine 5-hydroxytryptamine (5HT), produced an elevation of mood. On the basis of their results, Coppen, Shaw and Farrell (1963) treated a number of patients suffering from severe depressive illness with M.A.O.I. and half of this group also received an oral dose of a suspension of D L-tryptophan (214 mg./kg. body weight) for one week. The patients taking tryptophan and M.A.O.I. recovered more rapidly than those receiving M.A.O.I. alone both while they were on tryptophan and also subsequently. One explanation for these findings was that the combination of M.A.O.I. and tryptophan increased the amount of amines derived from tryptophan in the brain, and that it was this which was responsible for the therapeutic effect. If this were so, then there were several possibilities. The first was that the level of 5HT in the brain was low in depression and the combination of amine precursor and enzyme inhibitor brought it back to normal. Alternatively it may be that recovery occurred as a result of the presence of abnormally large quantities of 5HT in the central nervous system or even following the production of tryptamine, another amine derived from tryptophan.

Fluvoxamine, a Specific 5‐hydroxytryptamine Uptake Inhibitor

“…According to this view, activation of the central adrenergic functions is responsible for the psychoenergetic and motor-stimulating effects of antidepressants, whereas activation of serotoninergic functions is responsible for their mood-elevating properties. Confirmation of a possible role of a disturbance of 5-HT metabolism in depression comes from studies in which a decreased 5-HT content in the brain and a decreased 5-HT turnover has been demonstrated in patients (Shaw, Camps & Eccleston, 1967;van Praag, Korf & Puite, 1970;van Praag, Korf & Schut, 1973). It must be stated however that not all studies are in agreement concerning the occurrence of a reduced level of 5-HT metabolites in the cerebrospinal fluid of depressed patients (Papeschi & McClure, 1971).…”

Increase in Serotonin-1A Autoreceptors in the Midbrain of Suicide Victims with Major Depression—Postmortem Evidence for Decreased Serotonin Activity

“…In most, but not all, studies the content of serotonin or its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), is decreased in the brainstem of suicide victims (Shaw et al, 1967;Bourne et al, 1968;Pare et al, 1969;Lloyd et al, 1974;Beskow et al, 1976;Cochran et al, 1976;Korpi et al, 1986). Suicidal behavior is associated with lower levels of 5-HIAA in the CSF, and there is evidence that suicide risk can be predicted by low 5-HIAA in CSF after a suicide attempt (Nordstrom and Asberg, 1992).…”

L-5-Hydroxytryptophan in Depression: the First Substitution Therapy in Psychiatry?

“…The concentration of 5-HIAA (principal 5-HT metabolite) was like wise decreased. This could indicate reduced 5-HT synthesis in the brain (9,23).…”