DURING our investigations on the protein metabolism of schizophrenic patients, a number have been found who exhibited a specific, pathological pattern of emotional response to stress and abnormally high concentrations of a proteolyticenzyme inhibitor in the serum. The studies of West and associates 1 have demonstrated a relationship between the concentrations of this substance, rennin (human pepsin) inhibitor, and those of another, chymotrypsin inhibitor, and the rate of growth of cancer. The higher the titer of rennin inhibitor and the lower that of chymotrypsin inhibitor, the slower is the growth of the neoplasm. On the other hand, if the concentration of chymotrypsin inhibitor approaches or exceeds that of rennin inhibitor, the rate of growth is proportionately increased. Comparable relationships have been found between the relative concentrations of these enzyme inhibitors in active and in arrested pulmonary tuberculosis.2 Acute infections, physical traumas, and burns are accompanied by high chymotrypsinand low rennin-inhibitor titers. Anxiety states, as reactions to immediate, acute stresses, also follow this pattern when unaccompanied by hysterical defenses.3 On the contrary, high rennin-and low chymotryspin-inhibitor titers occur in a variety of chronic diseases. Pregnancy, hyperthyroidism, and, in some cases, hypertension are associated with significantly elevated rennin-inhibitor titers with a somewhat increased chymotrypsin-inhibitor titer.4 West and associates, in establish¬ ing the normal values for these proteolytic-enzyme inhibitors, noted the consistent occurrence of high rennin-and normal chymotrypsin-inhibitor titers in childhood.4The observation by one of the authors (C. E. T.) that the high concentrations of rennin inhibitor in the sera of schizophrenic patients occurred most frequently in the catatonic group suggested the importance of defining precisely the psychiatric From the Psychiatric Section, Neuropsychiatric Service, Veterans Administration Hospital.
Studies of protein metabolism have revealed well-defined deviations in the Concentrations of certain protein-splitting enzymes in the sera of patients with cancer( 1-3). This report concerns the existence of analogous enzymatic disturbances in the presence of emotional disorders. The enzymes in question are accompanied in the blood by excesses of their inhibitors. Measurements of the latter permit valid deductions referable to the particular enzyme systems. Chymotrypsin-inhibitor is one element of an enzyme system which correlates with the rate of protein destruction. For example, abnormal concentrations have been noted in the presence of cancer, infections, physical trauma and wasting diseases. The relief from anxiety afforded by prefrontal lobotomy (4) for the alleviation of intractable pain of cancer, is often followed by significant reductions in abnormally increased concentration of chymotrypsin-inhibitor. Electric convulsivetherapy provides comparable results.Therefore it becomes important to know the * Reviewed in the Veterans Administration and published with the approval of the chief medical director. The statements and conclusions published by the authors are the result of their own study and do not necessarily reflect the opinions or policy of the Veterans Administration.effect of emotional status alone upon the titer of chymotrypsin-inhibitor. Under certain circumstances its concentration in the serum correlates with the intensity of emotional reaction. In a series of 102 patients, the degree of anxiety experienced by each was estimated clinically (Fig. 1.) A graded scale of 5 divisions was employed: absence of anxiety and panic represented the extreme categories; slight, moderate and severe anxiety were defined in :the intermediate groups. Only schizophrenic psychotics, conversion hysterics and patients with acute anxiety states were included. A direct correlation between the degree of anxiety and elevations of chymotrypsin-inhibitor concentrations was found to exist in the last group alone. Patients with conversion hysteria exhibited no such relationships, and furthermore seldom demonstrated more than slight elevations in titer. On the other hand, schizophrenic psychotics showed highly variable enzymatic changes, some of which were directly related to the level of anxiety, while the majority were not. But, in this group high titers were obtained. I t then became imperative to investigate the possibility that the changes in protein metabolism might be associated with variations in adrenal function. The demonstration that the urinary excretion of the proteolytic enzyme, uropepsin, is an appropriate measure of adrenal activity, the titer directly paralleling adrenal function (5) , provided a satis-5. Spiro, H. M., Reifenstein, R. W., and Gmy, S . J.,
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