NEUROENDOCRINE RESPONSES TO LEVODOPA IN AFFECTIVE ILLNESS
SIR,—We have recently reported’ that the growth hormone
prolactin suppression following levodopa significantly greater in bipolar depressed patients than in unipolar depressed patients or controls. Dr Langer and Dr Sachar (March 19, p. 652) note that these results differ from their earlier study in which no unipolarbipolar difference was found, and suggest that the discrepancy might be due to the fact that in their study monoamines in the diet were not controlled, whereas we controlled (i.e., restricted) the intake of foods that contain large amounts of preformed amines (or foods which can alter amine metabolism). As
Langer and Sachar noted, other work from shown that in
bipolar depressed patients, shifting from
trolled to an uncontrolled monoamine diet resulted in a significant increase in the excretion of 3-methoxy-4-hydroxyphenylglycol (M.H.p.G. the urinary metabolite thought best to reflect brain noradrenaline metabolism) whereas M.H.P.G. excretion in normals is unaffected by dietary factors.2 Langer and Sachar cite this work as evidence that we may have inadvertently introduced a confounding variable by utilising a controlled monoamine diet in our study; in fact we chose to control monoamines in the diet because of evidence that uncontrolled variation in amine intake by depressed patients could introduce an extraneous source of variance, perhaps making subgroup differences more difficult to clarify. Langer and Sachar also note that other workers have shown that the G.H. response to insulin-induced hypoglycsemia is significantly different between unipolar depressed patients and controls,3 while we found no difference in G.H. response to levodopa between unipolar patients and controls. However, G.H. response to levodopa occurs primarily by means of a dopaminergic mechanism, whereas G.H. response to insulin-induced hypoglycxmia is mediated primarily through serotonergic and noradrenergic systems.4 Different neuroendocrine indices cannot be compared if the neuroendocrine responses are mediated by different monoaminergic neurotransmitters. Dr Mendlewicz and his colleagues (March 19, p. 652) did not find that the G.H. and prolactin responses to levodopa differed significantly between bipolar and unipolar depressed groups. They suggested that the differences between their study and ours might be secondary to differences in the sex and ovarian status of the two series of patients. In view of their emphasis on this issue (an issue which was highlighted in our paper’), it is curious that they did not state the relative numbers of premenopausal and postmenopausal women in their unipolar subgroup, thus making it difficult to assess to what extent ovarian status affected their unipolar-bipolar comparison. As we noted, G.H. response to levodopa is partly related to the level of circulatmg oestrogens,s and is highest in premenopausal women, intermediate in men, and lowest in postmenopausal women. The bipolar group studied by Mendlewicz et al. consisted largely of postmenopausal women; if their unipolar group was primarily premenopausal a unipolar-bipolar comparison might not be possible. In our series sex and overian status were unequally divided in the patient subgroups, so we analysed the premenopausal women separately and noted that the G.H. and prolactin responses to levodopa were significantly greater in bipolars than in unipolars or controls. Among premenopausal females, Mendlewicz et al. also noted a substantially higher G.H. response in bipolar compared with unipolar patients, although the number of patients was too small for statistical
analysis. 1. Gold,
P. W., Goodwin, F. K., Wehr, T., Rebar, R., Sack, R. Lancet, 1976, ii, 1308. 2 Muscettola, G., Wehr, T., Goodwin, F. K. Presented at the annual meeting of the American Psychiatric Association, held in Miami, Florida, in May, 1976. (New Res. Abstr. p. 8). Gruen,PH. and others. Archs gen. Psychiat. 1975, 32, 31. Frohman, L. A., Strachura, M. E. Metabolism, 1975, 24, 211. 5. Frantz, A. G., Rabkin, M. T. J. clin Endocr. Metab 1965, 25, 1470.
Our latest work suggests that some neurotransmitter metabolites in the cerebrospinal fluid differ significantly among males, premenopausal females, and postmenopausal females. Thus, in addition to oestrogen effects on G.H. responsiveness, there may be a primary neurotransmitter difference in depressed subjects based on sex and ovarian status, further underlining the need to consider this factor in the analysis of neuroendocrine data obtained from patients with a primary affective disorder. Other sources of variance in biological investigations in psychiatry (such as severity and phase of illness, stress, activity, time of -day, and time of year) should also be considered in the interpretation of neuroendocrine studies. These methodological issues can profoundly affect the outcome of any neuroendocrine study of affective illness. Clinical Psychobiology Branch, National Institute of Mental Health, Bethesda, Maryland 20014, U.S.A.
PHILIP W. GOLD FREDERICK K. GOODWIN
PSYCHIATRY, POLITICS, AND ETHICS SIR,—Your review (March 19, p. 632) of the book Psychiatry for Students of Medicine by Dr Lionel Corbett and me objects to the contention that a consideration of politics and ethics should play a small part in the education of the medical student in psychiatry. This is surely an "ivory tower" attitude in an era when, for example, Soviet psychiatry is under constant attack in the West for its alleged political abuses of psychiatry. The medical student is entitled to some information about the general development of psychiatry in both East and West, so that he can judge this and related issues for himself. You also object to our statement that "the Welfare State in Britain saps initiative and morale". The student of psychiatry should be aware also of the general political background to the lives of his patients, for one powerful factor in determining the mental health of a community is the political system or flux of contending political systems under which it operates. Since the present state of British society suggests to even the most sympathetic friend that initiative and morale are indeed sorely sapped in the managerial and professional classes, this must surely be relevant to doctors aiming to treat its citizens. It may be also a matter of concern for doctors in more fortunate countries such as the United States, whose influence can and should be exerted to prevent British mistakes, if only those made in health care and delivery, from being repeated over here. My excuse for calling some of the intellectual heroes of the New Left in psychiatry half-baked and evil is that it is about time someone said that they are, in a vein neither more nor less polemical than that used by Karl Popper in his discussion of the spiritual fathers of the totalitarian New Left-Plato, Hegel, and Marx.1 Department of Psychiatry, School of Medicine, University of Alabama in Birmingham, Birmingham, Alabama 35294, U.S.A.
D-PENICILLAMINE IN PRIMARY BILIARY CIRRHOSIS
SIR,—As former medical director of Dista Products I
read the paper by Dr Jain and his colleagues (April 16, p. 831). I would suggest that in any further studies of penicillamine in primary biliary cirrhosis early losses from adverse reactions to the drug might be reduced by using lower doses, at least in the early months of treatment. Jain et al. used 900 mg daily within a month, and it is not surprising that 3 patients had soon to be withdrawn because of rashes and nausea and vomiting.
1. Popper, K.
Open Society and Its Enemies. London,
same sort of thing used to happen when patients were given penicillamine for rheumatoid arthritis, until the drug was introduced more slowly.’Rheumatologists now introduce penicillamine at doses of 125 mg or 250 mg daily and step this up by similar amounts every 4-8 weeks. Unfortunately this regimen will not prevent late proteinuria, the frequency of which becomes low only if the daily dose is less than 500 mg. Some patients with rheumatoid arthritis have derived benefit from such low doses,2 and perhaps a low-dose regimen should be tested in primary biliary cirrhosis.
The Limes, 77 Southworth
25% of children with C.A.H. and normal in 21% of children with Wilson’s disease. Although hepatic copper content is occasionally increased in children with C.A.H., no untreated patient with C.A.H. in our series had a hepatic content >300 µg/g dry weight, while no untreated patient with Wilson’s disease had a hepatic copper content