Multicompartmental analysis of amino acids. III. Tyrosine in affective disorder.

Multicompartmental studies of tyrosine in patients suffering from affective disorders and controls gave estimates of 2 major pools of amino acid, together with the associated fractional clearance rates and fluxes. The 2 pools were considered provisionally to represent extracellular and intracellular tyrosine. The concentration of tyrosine in plasma (representing the extracellular pool) and fractional clearance rates from this compartment were normal in ill and recovered patients. The observed abnormalities were confined to the intracellular compartment and consisted of low concentrations of tyrosine in both depressed and recovered patients. In addition, fractional clearance rates from the intracellular compartment were raised in the depressed patients but had returned to normal after recovery. A comparison of these data with those of a similar study of tryptophan described previously suggested that alterations in compartmental volume or dietary differences could not explain the 2 sets of findings. The disturbances in tryptophan metabolism in unipolar affective disorder had led to reduced amounts of this amino acid in the extracellular space. In contrast, the concentration of tyrosine in this compartment was normal, presumably as a result of a metabolic adjustment to the lower amounts found in the intracellular pool. The presence of illness-dependent and illness-independent alterations in tyrosine metabolism in unipolar affective disorder, together with the earlier findings for tryptophan, may have a bearing on the aetiology of the illness.

Tricyclic antidepressants and tryptophan in unipolar depression.

Depressed patients (unipolar) were given one of the following combinations in an attempt to test aspects of the 'amine hypothesis' and to find a preferential therapy: (1) clomipramine; (2) clomipramine and tryptophan; (3) desipramine and clomipramine, and (4) desipramine and tryptophan. Treatment (2) should have given optimal potentiation of 5-HT neurones and (3) and (4) should have acted similarly on both serotoninergic and adrenergic pathways. In no group was there any evidence of accelerated recovery, indicating that the process of conversion to normal mood may be more complex than suggested by most versions of the amine hypothesis.

Multicompartmental analysis of amino acid. 1. Preliminary data on concentrations, fluxes, and flow constants of tryptophan in affective illness.

The study of tryptophan metabolism using compartmental analysis suggested differences between males and females, and between control subjects and patients with affective illness, patients treated with tricyclic drugs, and those established on lithium therapy. The total mass of tryptophan in the body may be reduced in people prone to affective disorder, and in depressed patients(ill and well)turnover of tryptophan seemed to be reduced. The reduction of concentration of tryptophan in compartment S2 in affective illness could affect protein synthesis.

Uptake and release of 14 C-5-hydroxytryptamine by platelets in affective illness.

In the search for paradigms of postulated abnormalities in indolamine function in the brain in affective disorders, 5-HT uptake and release was estimated in platelets from patients suffering from severe depressive illness. Neither of these measures was altered by the illness and the most likely explanation for the negative findings was that in this setting platelets are not a suitable model.