Diagnosis of schizophrenia

68

T U C S - S e p t e m b e r 1978

concentration, depolarize the Schwann cells and induce the release of acetyicholine from them. The subr~quent activation of the cholinergic receptor~ increases -~- + Depolarization the potassium permeability of the plasma membrane, and this results in the longlasting Schwann cell hyperp~lafization. Clearly, the interactions between the Disputes tend to be prolonged by allowing ~- ~ ; ~ H.~pc~polar~/ation Schwann cells and the axon are not the participants to use different definitions simple. Without a complete understanding of the probelm in dispute, and so state ~'I ('¢,fllr,,, + of the mechanisms involved, the functional cases which appear totally incompatible a -H(iT significance of the Schwann cell hyper- and yet remain logically consistent within polarizations cannot be assessed. Never- their own terms of reference. Such is the T~m¢ ( m i n i theless, the experiments herein reviewed debate set out in the first issue of Trends Fig. 4. Effect of the addition o f glutamate (L-zindicate that the acetylcholine system is in Neurosciences. between Professors ~'lutamic acid) at a final concentration o f i0 ~ M Kendell t and SzasE on the meaning of the to the e~ternal medium, on the membrane directly involved in the genesis of the potential of Schwann cells attached to axon.fre~ ~ long-lasting Schwann cell byperpolariza- diagnosis of schizophrenia. An analogy nerve ~bre sheaths exposed to control artificia~ tions following axonal excitation. They might be to set two sociologists to discuss ~ea ~ ater or to a !0 " M a-bungarotoxin (~-BGT~ also indicate the existence of special the place of the cat in our society, the first containing artificial sea water solution. The Schaann cell membrane potential response to structural links between Schwann cells defending its value in keeping down gtut~mate is biphasic. An initial transient hyper- and the axon in sites where the enzymatic vermin and providing company for the polarizing phase, sensitive to the toxin, is folloN "d activities of acetyicholinesterase and lonely, and the second decrying the use of by a sustained and rapidly reversible depolarizing adenosine triphosphata~ also appear to corporal pumshment as a means of #base insensitive to the toxin. be loctted. In addition, they show that maintaining naval discipline. The dispute hinges or h e value and u~s sechons, a diagram of a possible mechan- the Schwann cell membrane potential is which are attributed to a diagnosis. If a sensitive to glutamate, the putative neuroism of axon-Schwann cell chemical interdiagnosis is, in effect, a social definition of actions such as the one shogn in Fig. 5 transmitter of the giant axon. mental incapacity alone, then Professor ,na) be constructed: the etflux of potassium Szasz is right in that it will be used to label Acknowledgements from the excited axon is accompanied by The author is deeply grateful to Dr. subjects which a society wishes to reject. glutamate relea~. These two agents, in and also be used by the individual who the presence of a r,ormal external calcium Carlos Sevcik for his critical reading of the manuscript, and to Miss Isabel wishes to avoid responsibilit-, for his behaviour. Professor Szasz seems to wish Otaegui for her secretarial help. to simplify matters further by his curious Sea ~,ater Sch~.anncell [I A~,OII I statements that disorders of mental funcI Reading list' produced by clear physical d:~orders. ?j , I. Brzin, M.. Dettbarn, W. D., Rosenberg, P. tion and Nachmansohn, D. (1965J J. Cell Biol. and thereby not coming under the definition of a social diagnosis, are v.ever 26, 353-364. ' A c c [ " c h ° ' ' 1| c ")II'l 1 2. Dale, H. (1938) J. Mr. Sinai Hasp. N.Y. 4, treated against the patient's will and such F :cep~o~ I 401-429. sufferers are not generally excused fro=l the 3. Frankenhaeuser. B. and Hodgkin, A. L. responsibility for their actions. One -xon(1956) J. Physiol. (London) 131,341-376. 4. Kufflcr,S. W. and Nicholls, J. (3. (1976) in: ders whether he ever served as a medictl From Neuron to Brain. Sinauer Assoc. Inc., house officer if he can really believe that Sunderland, Ma~bachusetts, pp. 274-280. orgaaically confused patients calmJy ask $. Rawlins, F. A. and Villegas, J. 0978) J. the c~octor to set up a drip to return their Cell BioL (in press). met,~bolic s:ate to normal and restore their 6. Villegas, G. M. and Villegas, J. (1974) J. senses, and then wait quietly in the ward Hyperpolarization I Uitrastruct. Res. 46, 149--163. +.-,v,,,-f
~. . . . . . . . . .

"]

-

"

.............

Diagnosis of schizophrenia

],

i

o

~

.\,

EINvier/Nocth.Hoiland ~

Prea 1978

69

T I N S - September 1978

(laboured breathing), it describes a consis*.cnt pattern of behaviour which will be ex3erienced by the patient and observed h} the physician, it can, of course, be caused by different diseases in much the same way as can schizophrenia, but it remainsaserious symptom which generally responds to treatment. Since we know more about exertional dysponea than schizt,phrenia most doctors would want a more exact description which may be any of the following: (!) Based on organic pathology, e.g. bronchitis. (2) On metabolic pathology, e.g. reduced POz, raised pCO=. (3) Physiological pathology, e.g. carbon dioxide narcosis. (4) Acute precipitant, e.g. infection by Haemophilus influenzi. (5) Chronic exacerbate, e.g. addiction to tobacco. (6) Social effects, e.g. inability to work or to manage stairs. (7) Social complications, e.g. r e ~ i o n by faro :y leading to ex~ essive drinking and exposure to cokl air on returning from pubs, etc. Each of these descriptior, s would be of value to different specialists: thus diagnoses (2) and (3) would be of w=lue ~o doctors in the Intensive Care Unit treating the patient on artificial ventilation, d:agnosis (4) to the general physician prescribing antibiotic% diagnoses (I) and (6) to the general practitioner, and diagnosis (7) to the social worker. A similar set of descriptions could be applied to patients with schizophrenia. Nevertheless, most of these description~ are only of relevance to the individual professional within his clinical speciality, and when communicating with the general public doctors are more likely to use the general shorthand of chronic bronchitis, or schizophrenia. The fact that such a diagnosis may be then haken up by non.professionals and used for political purposes does not invalidate its medical function. For schizophrenia, the diagnosis serves three important medical functions: (I) It isolates a group of mental symptoms which appear together sufficiently consistently to suggest that they are produced by the same common physiological dysfunction. (2) By so defining the syndrome it becomes possible to study the nature of the dysfunction and to find treatments which restore the function to normal. (3) It provides a knowledge of ~he natural history of the condition against

which the treatments can be assessed and through which effective counselling given. It is no small triumph that a condition defined by its complex effects of perception should, many years later, be found to respond to a variety of drugs which all block dopamine transmission. Of course, there are exceptions, just as there are cases of exertional dysponea which do not respond to bronchodilation, but these exceptions do not invalidate the use of the diagnosis. We may then return to the attack on the diagnosis presented by Professor Szasz. He appears to Ix: rightly attacking the misuse of the term, but, in so-doing, rejects its medical value, a conclusion which is just as curious as if the second sociologist mentioned above recommended the mass extermination of pet cats because of his dislike of the whipping of sailors. J. KELLE'Vr

Department of Psychiatry. St George's Hospital Medical School, London .~WI7, U.K. I Kendell, R. E. (1978) Trends NeuroSci. I. 24--26. 2 Szasz,T. (1978) Trends Neuro.$cl.. I. 26 28.

Concept of Schizophrenia I was qmte flattered to be. taken to task by Thomas Szasz (Trends AeuroSci I, 27) for making "a fundamental categorical error" in relatmg disorders of the mind to disorders of the human brain. Dr Szasz says that the relationship of brain to mind is of a different order than the relationship of kidney to urine. I was not aware that the mind was a transudate of the brain, if Dr Szasz wants to regard the mind as something as tangible as urine he Js most welcome to do so, but those of us attempting to develop a scientific psychiatry prefer to concentrate on the brain as the target of our researches. M. H. LADER

Institute o f Psychiatry, London, U.K.

T I N S E d i t o r i a l Office 14A R e g e n t S t r e e t Cambridge CB2 IDB, U.K.

Carnosiae as a transmitter The biochemical evidence indic.tting a transmitter role for carnosine in the mammalian olfactory bulb presented by Frank Margolis ~ is indeed compelling. However, electrophysiological evidence obtained in thisz.4 and other laboratories (R. A. Nicoll; S. M. Crain: unpublished observations) suggest that carnosine is not the transmitter released from primary olfactory nerve (PAN) terminals. Although the response of mitral cells (the major olfactory neurones) is rather complex l.s, electrical stimulation of ihe P a N induces a clear monosynaptic excitation of these cells=.3.L Thus they usually fire a single short latency spike in response to an electrical shock appl;,.d to the nerve. Mitral cells would therefore be expected to be excited by carnosine when applied iontophoreticaily into the vicinity of their cell bodies (or more especially their primar/ dendritic tufts). The responses observed, however, have been extremeb variable, more closely r~.'sembling response:, to natt~ral rather than electrical stimulation of the system. Carnosine did indeed increase the firing rate of some mitral cells. but decreased the activity of others, whil,,t many did not respond at all. Using a similar experimeata! design, Roger Ntcoll has obtained ~ompa:able results and Stanley Crain has found carnosine to be without effect on mJtral cell activity when "bath applied' to an in vitro preparation of an olfactory bulb explant The role of carnosine in the olfactory system thus remains unclear in common with many other peptides in the central nervous system whose electrophy, iological action doesn't live up to the expectation ot' anatomical and biochemical colleagues. I. MacL.~od. hl. K. (1976) Fxp. Brain Res 25, 25f~266. 2. MacLeod, N. K. (1978) in: R. W. Ryall ane J. S. Kelly(eds) lantophoresis and Transmitter mechanisms in the Mammalian Central Nervous System, Elsevier/ Noft h-Holland Biomedical Press, Amsterdam and New York, pp. !17 119. 3. MacLeod, N. K. and Lowe, G. A. (1976) Exp. Brain Res. 25, 267 278. 4. MacLeod, 'q. K. and Straughan, D. W. (1978) Exp. Brair, Res. (in p?ess). 5. Margohs, F. L. (197~) Trends He;,roSci. !, 42-44. 6. Mathews, D. F. (1972) Brain Res. 47.,3r,9--400. 7. Shepherd, G. M. (1963) 3'. P.~ysioi. ~London) 168. 89-100. t~. K. MACLEOD

Department of Pharmacology, School o[ Pharmacy. l.omtbn WCIN lAX. U.K.