Decreased urinary output of tyramine and its metabolites in depression.

Despite dramatic clinical improvement in about one-third of a group of severely depressed, medication-resistant patients one year after modified leucotomy, their relative decrease in conjugated and free tyramine output after an oral tyramine load remained unchanged and abnormal. Whilst a direct deficit in intestinal tyramine-conjugating ability still needs to be finally ruled out, this appears most compatible with a deficit due to bodily metabolic failure, perhaps a deficit in membrane transport which could be an essential aspect of the depressive illness syndrome. Attention is drawn to a similar defect in migraine. The two illnesses may represent a common predisposition which an appropriate triggering mechanism may transform to the florid disease. Biochemical detection of such vulnerability may have important diagnostic and predictive significance.

Studies of endocrine activity, plasma tryptophan and catecholamine excretion on psychosurgical patients.

The Geoffrey Knight Psychosurgical Unit admits patients on a regular basis and thus offers special opportunities for studying severely ill psychiatric cases, all having one particular treatment under relatively controlled conditions. The opportunity has been taken to repeat various metabolic studies previously reported to be abnormal in some psychiatric illnesses. In the present investigation several measures of endocrinological activity were studied, as was plasma tryptophan, both free and bound. None of these data confirmed reports of abnormalities and neither did the values found at operation help to predict clinical outcome 1 year later, which was another possibility. Urinary catecholamines were also measured and 2 weeks after operation. Male patients, regardless of diagnosis, showed a mean increase in adrenaline output after operation compared with the pre-operative value and this was significantly different from the females, who showed a small mean decrease. The depressed patients showed a significant reduction in noradrenaline excretion after operation compared with before operation and this trend was enhanced in those of good outcome at 1 year, the difference from those who responded poorly being significant. It could be that the ventromedial lesion that is produced alters noradrenaline metabolism or autonomic activity in depression and this possibility merits further study.

Precursors and metabolites of 5-hydroxytryptamine and dopamine in the ventricular cerebrospinal fluid of psychiatric patients.

Tryptophan and 5-hydroxyindoleacetic acid (precursor and metabolite respectively of 5-hydroxytryptamine) were determined in ventricular CSF of psychiatric patients undergoing stereotactic subcaudate tractotomy. Tyrosine and homovanillic acid (precursor and metabolite respectively of dopamine) were also determined. Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate. This leads to lower 5-hydroxyindoleacetic acid concentrations in depression and higher concentrations in anxiety and agitation.