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 intracellular 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 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.

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.