[PDF] Tryptophan metabolism in depression | Semantic Scholar (2024)

The data in this report do not support the suggestion of increased metabolism of TRYP along the kynurenine pathway in depression, and there were no significant differences in the basal urinary excretion between the two patient populations.

It is concluded that the apparent volume of distribution of tryptophan is reduced in depressive individuals, consistent with other findings of increased protein-binding of plasma tryPTophan and reduced CSF tryptophile levels in depressive patients.

It is concluded that the absorption, the plasma clearance, and the degradation to kynurenine of loading doses of l-tryptophan are normal in depressed patients.

The results are discussed with reference to known abnormalities of tryptophan metabolism in depressive illness and in particular to the 5-hydroxytryptamine uptake characteristics of blood platelets in depressive patients.

The excretion of xanthurenic acid only at 2 weeks correlated significantly with the anxiety and depression scores at 4 weeks, making prediction of clinical impovement possible.

Findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects, and there is no evidence of altered production of serotonin as 5-HIAA concentration was unchanged.

It is strongly indicated that brain serotoninergic function can be disturbed in depressed patients and, thus, lend support to the serotonin deficiency hypothesis in depression.

Examining the concentration of 5HIAA in the lumbar CSF of patients suffering from affec¬ tive disorders found increasing evidence of an abnormality of indoleamines in the affective disorders, though the probenecid test showed evidence of decreased rate of 5-HT synthesis in these conditions.

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Two rapidly cycling manic-depressive patients were studied in the hospital by daily clinical assessment of their psychological state, and by daily measurement of 24-hour urinary 17-hydroxycorticosteroid excretion to further investigate adrenal cortical activity in manicdepressive illness.

The data suggest that the liver enzyme tryptophan pyrrolase has a circadian rhythm in man similar to that already described in mice in a previous study.

Recent researches in the affective psychoses did not reveal significant differences between patients and normal controls in the urinary output of 5-hydroxyindoleacetic acid (5-HIAA) before or after an oral 5-Hydroxytryptophan load.

The existence of a definite relation between the metabolism of aromatic amino acids and mental disease, and between indole compounds and schizophrenia is suggested, and the fraction of ingested tryptophan which is metabolized via serotonin to give 5hydroxyindoleacetic acid is studied.

Findings suggest that elevation of one or both of the above amines is responsible for the therapeutic effect of MAOI, and that their insufficiency may be responsible for symptoms of the disease.

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.

The simplest explanation of the findings is that they are a nonspecific stress response, but they have found normal results in patients equally ill from other causes, and suggest that there might be an alternative mechanism, possibly outside the pituitary-adrenal axis.

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