Psychosomatic Medicine JOURNAL OF THE AMERICAN PSYCHOSOMATIC SOCIETY
Editorial Are "Psychosomatic" Diseases Diseases of Regulation? Evidence has begun to accumulate that four of the diseases that have been a major focus of concern of investigators in the field of psychosomatic medicine are characterized by specific disturbances of physiological regulatory mechanisms that may constitute a predisposing risk factor. However, general statements of this kind must be made with caution: The same diseases have also been called stress diseases, or diseases of homeostasis. Although such concepts have been fruitful for research, they lack specificity. Therefore, it is incumbent on anyone who proposes some new term for these diseases to specify what is meant by a disease of regulation. Elevations of pepsin and hydrochloric acid occur in peptic ulcer disease even when the disease is not active. However, it is not the raised levels of hydrochloric acid that are of moment but rather it is an altered relationship between gastrin and hydrochloric acid that may be the interesting variable in some forms of the illness. Normally, as hydrochloric acid levels rise in the stomach, gastrin levels fall— a classical example of a negative feedback system. In peptic ulcer disease, it now has been shown that this negative feedback system has failed: In the presence of high levels of hydrochloric acid, gastrin levels are normal, not depressed (1). In essential hypertension, plasma renin activity is distributed in a Gaussian manner. Theoretically, the distribution of urinary aldosterone levels should follow a similar distribution, as plasma renin activity determines levels of angiotensin II activity, which is the main (but not the only) regulator of aldosterone levels in plasma and urine. The regulation of aldosterone occurs in a positive feedback manner: Low levels of plasma renin activity should bespeak low urinary aldosterone levels. Yet Brunner and his colleagues (2) have found that 14%-23% of 219 hypertensive patients with plasma renin activity at the low end of the distribution curve had either normal or elevated levels of urinary aldosterone. Conversely, in 8 %-12 % of hypertensive patients with high plasma renin activity, normal (not the expected elevated) levels of urinary aldosterone were found. Depending on the strictness of the criteria employed, 29%-53% only of 219 patients showed the expected relationship between plasma renin Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975) Copyright ° 1975 by the American Psychosomatic Society, Inc. Published by American Elsevier Publishing Company, Inc.
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activity and urinary aldosterone levels. This result suggests that in a proportion of patients with essential hypertension the regulatory reJationship between renin, angiotensin II and aldosterone is altered. The serum of many patients with rheumatoid arthritis contains rheumatoid factors. These heterogeneous antibodies of the IgG class that complex with other antibodies (in other words, they act as if they were antigens) are also present in other illnesses, in patients who have no arthritis but may have rheumatoid skin nodules, and they occur more frequently in the well relatives of patients with rheumatoid arthritis than in the general population. The incidence of rheumatoid arthritis is much enhanced in diseases characterized by a dejiciency in the production of IgG antibodies. Thus, persons who are predisposed to produce excessive or deficient amounts of IgG antibodies are at risk for rheumatoid arthritis. But it is not the excess or deficiency that may be the crucial factor but rather an imbalance between the amount of antigen (in this instance the IgG antibody) and the amount of antibody may be of crucial significance in such instances. The consequence of such an imbalance is a failure to clear the antigen-antibody complexes from the body and their deposition, e.g., in blood vessels (3). One might conclude that the regulation of the disposition of these complexes may place their host at risk for the illness. There is a considerable body of evidence that, at least, in some patients with bronchial asthma, there is an inherent tendency to bronchoconstriction due to a deficiency in /3-adrenergic receptor activity and bronchoconstrictor activity due to a-adrenergic receptor and parasympathetic activity. Thus, when the functioning of the /3-adrenergic system is inadequate or deficient, the balance of these regulating mechanisms is biased in various degrees toward bronchoconstriction, which is easily demonstrated, at least, in asthmatic children (5-7). We do not know why these autoregulatory or regulatory systems in these four diseases are altered or biased in one or the other direction. If they are studied following the onset of the disease one cannot ascertain whether they antecede the disease, are present at its inception or are a consequence of some other process. With our present techniques it should, however, be possible to determine which of these three possibilities actually obtain. HW
REFERENCES 1. Trudeau WL, McGuigan, JE: Relations between serum gastrin levels and rates of gastric hydrochloric acid secretion. New Engl J Med 284:408^412, 1971 2. Brunner HR, Laragh JH, Baer L, et al.: Essential hypertension: Renin and aldosterone, heart attack and stroke. New Engl J Med 286:441-449, 1972 3. Dixon FJ, Feldman J, Vazquez J: Experimental glomerulonephritis. J Exp Med 113:899-920, 1961 290
Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975)
EDITORIAL 4. Szentivanyi A: Beta adrenergic theory of atopic abnormality in bronchial asthma. J Allerg 42:203-232, 1968 5. Jones RS: Assessment of respiratory function in the asthmatic child. Br Med J 2:972-975,1966 6. Pinkerton P: Correlating physiologic with psychologic data in the study and management of childhood asthma. J Psychosom Res 11:11-25, 1967 7. Pinkerton, P, Weaver CM: Childhood asthma, in Hill OW, Modern Trends in Psychosomatic Medicine, Vol 2. New York, Appleton-Century-Ciofts, 1970
Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975)
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Editorial Are "Psychosomatic" Diseases Diseases of Regulation? Evidence has begun to accumulate that four of the diseases that have been a major focus of concern of investigators in the field of psychosomatic medicine are characterized by specific disturbances of physiological regulatory mechanisms that may constitute a predisposing risk factor. However, general statements of this kind must be made with caution: The same diseases have also been called stress diseases, or diseases of homeostasis. Although such concepts have been fruitful for research, they lack specificity. Therefore, it is incumbent on anyone who proposes some new term for these diseases to specify what is meant by a disease of regulation. Elevations of pepsin and hydrochloric acid occur in peptic ulcer disease even when the disease is not active. However, it is not the raised levels of hydrochloric acid that are of moment but rather it is an altered relationship between gastrin and hydrochloric acid that may be the interesting variable in some forms of the illness. Normally, as hydrochloric acid levels rise in the stomach, gastrin levels fall— a classical example of a negative feedback system. In peptic ulcer disease, it now has been shown that this negative feedback system has failed: In the presence of high levels of hydrochloric acid, gastrin levels are normal, not depressed (1). In essential hypertension, plasma renin activity is distributed in a Gaussian manner. Theoretically, the distribution of urinary aldosterone levels should follow a similar distribution, as plasma renin activity determines levels of angiotensin II activity, which is the main (but not the only) regulator of aldosterone levels in plasma and urine. The regulation of aldosterone occurs in a positive feedback manner: Low levels of plasma renin activity should bespeak low urinary aldosterone levels. Yet Brunner and his colleagues (2) have found that 14%-23% of 219 hypertensive patients with plasma renin activity at the low end of the distribution curve had either normal or elevated levels of urinary aldosterone. Conversely, in 8 %-12 % of hypertensive patients with high plasma renin activity, normal (not the expected elevated) levels of urinary aldosterone were found. Depending on the strictness of the criteria employed, 29%-53% only of 219 patients showed the expected relationship between plasma renin Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975) Copyright ° 1975 by the American Psychosomatic Society, Inc. Published by American Elsevier Publishing Company, Inc.
289
EDITORIAL
activity and urinary aldosterone levels. This result suggests that in a proportion of patients with essential hypertension the regulatory reJationship between renin, angiotensin II and aldosterone is altered. The serum of many patients with rheumatoid arthritis contains rheumatoid factors. These heterogeneous antibodies of the IgG class that complex with other antibodies (in other words, they act as if they were antigens) are also present in other illnesses, in patients who have no arthritis but may have rheumatoid skin nodules, and they occur more frequently in the well relatives of patients with rheumatoid arthritis than in the general population. The incidence of rheumatoid arthritis is much enhanced in diseases characterized by a dejiciency in the production of IgG antibodies. Thus, persons who are predisposed to produce excessive or deficient amounts of IgG antibodies are at risk for rheumatoid arthritis. But it is not the excess or deficiency that may be the crucial factor but rather an imbalance between the amount of antigen (in this instance the IgG antibody) and the amount of antibody may be of crucial significance in such instances. The consequence of such an imbalance is a failure to clear the antigen-antibody complexes from the body and their deposition, e.g., in blood vessels (3). One might conclude that the regulation of the disposition of these complexes may place their host at risk for the illness. There is a considerable body of evidence that, at least, in some patients with bronchial asthma, there is an inherent tendency to bronchoconstriction due to a deficiency in /3-adrenergic receptor activity and bronchoconstrictor activity due to a-adrenergic receptor and parasympathetic activity. Thus, when the functioning of the /3-adrenergic system is inadequate or deficient, the balance of these regulating mechanisms is biased in various degrees toward bronchoconstriction, which is easily demonstrated, at least, in asthmatic children (5-7). We do not know why these autoregulatory or regulatory systems in these four diseases are altered or biased in one or the other direction. If they are studied following the onset of the disease one cannot ascertain whether they antecede the disease, are present at its inception or are a consequence of some other process. With our present techniques it should, however, be possible to determine which of these three possibilities actually obtain. HW
REFERENCES 1. Trudeau WL, McGuigan, JE: Relations between serum gastrin levels and rates of gastric hydrochloric acid secretion. New Engl J Med 284:408^412, 1971 2. Brunner HR, Laragh JH, Baer L, et al.: Essential hypertension: Renin and aldosterone, heart attack and stroke. New Engl J Med 286:441-449, 1972 3. Dixon FJ, Feldman J, Vazquez J: Experimental glomerulonephritis. J Exp Med 113:899-920, 1961 290
Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975)
EDITORIAL 4. Szentivanyi A: Beta adrenergic theory of atopic abnormality in bronchial asthma. J Allerg 42:203-232, 1968 5. Jones RS: Assessment of respiratory function in the asthmatic child. Br Med J 2:972-975,1966 6. Pinkerton P: Correlating physiologic with psychologic data in the study and management of childhood asthma. J Psychosom Res 11:11-25, 1967 7. Pinkerton, P, Weaver CM: Childhood asthma, in Hill OW, Modern Trends in Psychosomatic Medicine, Vol 2. New York, Appleton-Century-Ciofts, 1970
Psychosomatic Medicine Vol. 37, No. 4 (July-August 1975)
291
