1024

Letters

to

the Editor

C.S.F. &bgr;-ENDORPHIN IN SCHIZOPHRENIA

SIR,-Involvement of &bgr;-endorphin in schizophrenic disorders has repeatedly been speculated on’ though the evidence in support of this hypothesis is only indirect: p-endorphin injected intraventricularly into rats induced catatonia;2.3 blockade of endogenous endorphins by naloxone reduced auditory hallucinations in some schizophrenic patients;4.Sand in the cerebrospinal fluid (c.s.F.) of patients with chronic schizophrenia, variations of enkephalin-like material (unidentified degradation products probably formed from endorphins) have been reported, depending upon phase and treatment of the disease.6-8 We have directly assessed the role of radioimmunoassayable C.S.F. p-endorphin in schizophrenia. We investigated five schizophrenics in the acute state of the disease: the patients were paranoid with auditory hallucinations (mean age 42 years, range 29-75). C.S.F. samples were kindly provided by Dr Untereiner, Psychiatric District Hospital, Ansbach. We also studied seven chronic schizophrenics (mean age 71, range 62-77) diseased for more than 10 years and presenting in a predominantly defective residual state. All patients had been receiving neuroleptic drugs. Ten patients (mean age 50, range 21-71) with neurological symptoms mainly due to discal hernia and seven subjects (mean age 41, range 21-60) in whom neurovertebral disease could be excluded were studied as controls. c.s.F. samples were taken by lumbar puncture and immediately frozen with dry ice and stored at -20°C until 3-endorphin analysis. In a first step, p-endorphin was extracted from samples using adsorption to silicic acid, washing with ether, and desorption by acidic acetone, essentially as described by Hollt et al.9 Subsequently, extracts were analysed C.S.F.

*Student’s

t-test

&bgr;-ENDORPHIN

(mean+s.E.mt.)

on

LEVELS

comparison with normal controls.

for -endorphin by a specific and sensitive radioimmunoassay. Antisera were raised by immunisation of rabbits with synthetic -endorphin (Paesel, Frankfurt/Main) coupled to bovine albumin with carbodiimide. At a final dilution of 1/32 000, approximately 50% of radioiodinated -endorphin label was bound by the antiserum used. The detection limit of the assay was 10 pg per tube. As the table shows, acute schizophrenics presented with im1. Lancet, 1978, ii, 819. 2. Bloom, F., Segal, D., Ling, N., Guillemin, R. Science, 1976, 194, 630. 3. Jacquet, Y. E., Marks, N. ibid. p. 632. 4. Watson, S. J., Berger, P. A., Akil, H., Mills, M. J., Barchas, J. D. ibid.

1978, 201, 73. 5. Janowsky, D., Judd, L., Huey, L., Roitman, N., Parker, D., Segal, D. Lancet, 1978, ii, 320. 6. Terenius, L., Wahlström, A., Lindström, L., Widerlöv, E. Neurosci. Lett. 1976, 3, 157. 7. Lindström, L. H., Widerlöv, E., Gunne, L. M., Wahlström, A., Terenius, L. Acta psychiat. scand. 1978, 57, 153. 8. Dupont, A., Villeneuve, A., Bouchard, J. P., Bouchard, R., Mérand, Y., Rouleau, D., Fabrie, F. Lancet, 1978, ii, 1107. 9. Höllt, V., Przewlocki, R., Herz, A. Naunyn-Schmiedeberg’s Arch. Pharmacol. 1978, 303, 171.

munoreactive c.s.F. p-endorphin concentrations about ten times higher than those of controls. In contrast, -endorphm levels in chronic schizophrenics were about 50% of normal. These data are compatible with the view that altered endorphin homceostasis does play a role in the acute as well as in the chronic state of schizophrenia. c.s.F. p-endorphin analysis may prove to be a helpful differential diagnostic tool in clinical

psychiatry. Departments of Medicine and Pharmacology, University of Erlangen-Nürnberg, and Psychiatric District Hospital, Erlangen, Germany

W. DOMSCHKE A. DICKSCHAS P. MITZNEGG

RESEARCH INTO LEAD POLLUTION

SIR,-In their letter of Feb. 10 (p. 324) Professor Clayton and her colleagues state that the Department of Health and Social Security asked them to comment on two papers dealing with low-level lead and neuropsychological function. The papers in question were those of my group and that of Dr Oliver David. Clayton et al. then state: "We prepared a report that was critical, but adequate appraisal was difficult because full details of the work had not been published". Their fourpage mimeographed critique did not find that either report "supported a sound case for a major or minor effect of a moderate amount of lead on the intelligence or behaviour of children." Clayton et al. were right to refer to difficulties of appraisal; the only written report of my group’s work at that time was a 250-word abstract. Yet they faulted our study primarily because it overlooked certain variables reflecting parental attention and neglect. In fact, these important variables were the subject of particular and extensive scrutiny, and I would have been pleased to share these data (now published in the full paper2) with Clayton et al. had they asked me to. It seems to me that the task of criticising another’s work implies an obligation to maximum information before issuing an evaluation. The British and American postal systems are often the subject of abuse, but they periodically work. In October, two months after the critique of Clayton et al. was distributed, I received two copies by airmail from U.K. colleagues, but none from Clayton et al. A subject as significant to the public health as low-level lead and brain function deserves careful and open review. I hope that all students of the subject will judge the conclusions of my group’s work, and that of others, on the basis of the fully published record. Children’s Hospital Medical Center, Boston, Massachusetts 02115, U.S.A.

HERBERT L. NEEDLEMAN

SIR,- Thank you for providing

me with an opportumtv to Dr Needleman’s letter and his published Firstly, I should like to congratulate Dr Needleman and his co-workers on the comprehensiveness of their study. It has already been acknowledged that he should have been sent a copy of comments prepared for the Department of Health once it had been agreed these could be circulated more widely, and I should like to repeat my regret that this did not happen. The comments incidentally, did refer to the fact that they were based on a preliminary report. Nevertheless, many of the reservations I have expressed earlier remain now that I have seen the fuller version of this

comment on

paper.

Needleman, H. L., Gunnoe, C., Leviton, A., Peresie, H. Society for Pedatric Research, New York, April 26, 1978; abstr. 2. Needleman, H. L., Gunnoe, C., Leviton, A., Reed, R., Peresie, H. Mahen C., Barrett, P. New Engl. J. Med. 1979, 300, 689. 1.

C.S.F. beta-endorphin in schizophrenia.

1024 Letters to the Editor C.S.F. &bgr;-ENDORPHIN IN SCHIZOPHRENIA SIR,-Involvement of &bgr;-endorphin in schizophrenic disorders has repeatedly...
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