Plasma amino acids in patients with senile dementia and in subjects with Down's syndrome at an age vulnerable to Alzheimer changes.

Plasma concentration of tryptophan, tyrosine, leucine and thiamine were reduced in senile dementia of Alzheimer type. In Down's syndrome, where Alzheimer-type histology appears consistently at an early age, there was a definite type of abnormality, raised concentrations of isoleucine, leucine, phenylalanine and cystine. Because of the competition between amino acids for transfer into the brain, either or both of these types of change could lie in the aetiological chain underlying the development of Alzheimer pathology. Alternatively, these patterns could reflect the requirements of aberrant central/peripheral protein turnover.

The effect of carbamazepine and lithium on remission from affective illness.

Times in remission from affective illness were prolonged during treatment with lithium carbonate and carbamazepine, but lithium was the more effective. Similar global scores for the two drugs suggested that other factors may determine their acceptability.

Tryptophan and nutritional status of patients with senile dementia.

The nutritional status of 23 severely demented patients was compared with that of 23 similarly aged controls in the community. A 3-day weighed intake on all subjects showed lower mean intakes of energy, protein, ascorbic acid and nicotinic acid in the mean intakes of energy, protein, ascorbic acid and nicotinic acid in the patient group. This group had lower levels of plasma ascorbic acid and red cell folate and of urinary N-methylnicotinamide excretion relative to creatinine. Over a third of both controls and patients had evidence of thiamin deficiency, as judged by a raised percentage erythrocyte transketolase activity. An earlier finding in patients with senile dementia of reduced fasting plasma concentrations of tryptophan was confirmed for total and protein bound fractions. With the possible exception of ascorbic acid, the data could not be explained satisfactorily in terms of intake. It is suggested that the association between the phenomena of aging, senile dementia and nutritional status merits further investigation.

Tryptophan, affective disorder and stress. An hypothesis.

Patients suffering from unipolar illness and anticipating a complex investigation, or the first of a series of ECTs, had lower total tryptophan levels than control subjects under the former circumstances. This suggested a qualitative or quantitative difference in response to stress, associated with a fall in the amino acid level. It was hypothesized that this might selectively decrease synthesis of both protein and 5-HT in serotoninergic neurones.

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.

Distribution of tryptophan and tyrosine in unipolar affective disorders as defined by multicompartmental analysis.

As requirements for tryptophan for synthesis of protein and 5-hydroxytryptamine were comparable in rat brain, during depletion of tryptophan there could be competition between the two pathways for the amino acid. This implied that tryptophan should be rate-limiting for protein synthesis and this was found in the short term when concentrations of the amino acid were reduced in rats. Multicompartmental studies of tryptophan and tyrosine in controls and patients subject to unipolar depression defined two main pools of the amino acid provisionally assigned to extracellular and intracellular spaces. For tyrosine, mean values for the extracellular space were comparable to those of controls. The concentration of tyrosine was low in the intracellular space in both depressed and recovered patients, but the raised fractional clearance rates for this compartment during depression had returned to normal on remission. Plasma tryptophan concentrations were significantly reduced in depression with intermediate values after recovery. This suggested that the procedure used may have been mildly stressful and that this had evoked an idiosyncratic response to the stress in the depressed patients, which was characterized by inability to maintain concentrations of this amino acid in plasma. The findings for both amino acids may have a bearing on the aetiology of unipolar affective disorder.

Multicompartmental analysis of amino acids: II. Tryptophan in affective disorder.

Two of the tryptophan pools in the body and their associated fluxes, as defined by multicompartmental analysis, were studied in patients with unipolar affective disorder, bipolar patients (manic) and control subjects. The 2 pools were tentatively associated with extra- and intra-cellular compartments. The investigations were performed fasting and may have been mildly stressful. Under these conditions the concentration of tryptophan in plasma and perhaps amounts in the extracellular space were reduced in unipolar depression, with intermediate values after recovery. Some model parameters were lower in females than in males. The results in unipolar affective disorder were interpreted in terms of a previously presented hypothesis that this illness may result in an idiosyncratic response to stress in which patients are unable to maintain normal amounts of tryptophan in the body. In manic patients extracellular levels of tryptophan were unchanged but intracellular and total quantities of 'freely available' tryptophan may have been reduced.