In the world of mental diseases schizophrenia may well be termed “the sickness that destroyeth in the noonday.” Although the replacement of Kraepelin's nomenclature of “dementia praecox” by Bleuler's term, “schizophrenia,” has carried with it a general recognition that the chance of recovery is better than had been originally anticipated, the doom of those who do not recover is amongst the most dreadful meted out by any disease. It so frequently means a body apparently fully alive with a mind permanently impaired or virtually dead. Despite the obvious desirability of assessing the prognostic chances of the individual case, the statistical works published up to date have failed to establish agreement as to how this may be done. The object of this paper is to combine a detailed examination of the literature with a personal study of the histories of over 100 cases of schizophrenia in an effort to reach a definite conclusion in this matter. The paper will be divided into the following parts: I, a detailed survey of the literature; II, the outcome of 120 cases studied by myself; III, a comparison of remission rates and prognostic factors in cases treated by cardiazol.

In a study on chorea, tics and compulsive utterances, Creak and Guttmann (1) discussed some problems of the inter-relation of organic neurological and neurotic symptoms. They showed that residuals, latent or manifest, of neurological diseases of the motor system may be instrumental in shaping the clinical picture of neuroses. There is generally no difficulty in demonstrating such interrelations, if the neurological anomalies are of a well-known type and clear cut in onset. Pareses, peripheral or central, or aphasic disorders, are generally not difficult to recognize where they are the nucleus of a neurotic picture, and not much objection is encountered if one tries to assess their importance, pathogenetic or pathoplastic, in a given clinical picture. This, however, is difficult where less well known syndromes are concerned, such as apraxic or agnosic pictures, or where beginning or end are gradual and the whole picture less clearly defined, as in disturbances of the extra-pyramidal motor system. To recognize an early stage of Parkinsonianism within a depression or other “neurotic” illness is not easy. The same is true of mild extra-pyramidal hyperkinetic states, partly because they may be so similar to normal movements (pseudo-purposeful), and partly because the milder anomalies as seen in early or later stages (and in abortive cases) are little known.

The way in which schizophrenics react to physical illness and injury is a problem worthy of study, especially at the present time when schizophrenia is being so widely treated by methods which bring about profound changes of the physical state. Although schizophrenics, recent and chronic, are very susceptible to physical illness and form a considerable part of the sick population of the average mental hospital, this question has not attracted a great measure of attention. A survey of the schizophrenic population of a mental hospital suggests that there is an apparent lack of specific psychotic reactions to physical illness, so that it would seem as if schizophrenics react to physical illness either in a normal way or more commonly with indifference. It is true that certain paranoid patients include complaints of physical disturbances in their systems of delusions, but as a rule, even in these cases, there is no specific reaction to physical illness, which like other experiences enters into the world of imagination in which the patient exists.

The problem of the differentiation between neurosis and psychosis has given rise to much confused literature and discussion. This is particularly true of those cases in which anxiety or depression is the outstanding feature of the illness, and which do not show any gross symptoms of psychotic illness. Such confusion as exists appears to be due to a variety of causes. For example, the social implications of psychotic illness tend to favour a diagnosis of neurosis in many of the milder cases. Again, the same diagnostic terms are often used with quite different meanings by different workers. An even more potent cause of difficulty is the temptation to search for fixed disease entities in psychiatry which can be sharply separated one from the other.

During recent years so much has been written about convulsive therapy that it would seem rash to burden still further the very extensive literature on this subject. Nevertheless, in spite of the admirable work that has been done, it cannot be said that the implications of convulsive treatment are fully understood, nor that the fullest possible use has been made of this treatment for research into the pathophysiology of epilepsy. Furthermore, the recent introduction by Cerletti and Bini (1) of a method of treatment with electrically produced epileptic fits has increased still further the scope of research. I have had at my disposal case material provided by the treatment of various forms of mental disorder with cardiazol for more than two years, and with the electrical method in collaboration with Mr. Grey Walter for about six months. This has enabled me to conduct certain investigations of a sort that have received little or no attention hitherto, and to make observations covering various aspects of the physiology and psychopathology of induced epileptic states.

Unhydrolysed urine does not usually give a strong Millon's reaction in healthy people, but various workers have reported a strongly positive Millon's reaction in the unhydrolysed urine of mentally defective patients. Schemer (1927, 1928) worked up such urines for tyrosine with negative result, and also showed that the reaction was not due to free phenol or oxy-acid. He claimed (1929) to have isolated the substance responsible, but did not identify it. Lieb and Schadendorff (1929) showed that the substance isolated was impure sodium acetate formed in the method of isolation. The mystery of the substance giving the Milon's reaction was thus left unsolved.

The behaviour of animals and man may be approached from many points of view, but there is one feature of their behaviour which is outstanding in its importance and in its difficulty. I refer to the peculiar “adaptiveness” of animals' behaviour. The concept is vague, but everyone knows, roughly at least, what is meant by it. It is certainly one of the most remarkable features of animal behaviour. In psychiatry its importance is central, for it is precisely the loss of this “adaptiveness” which is the reason for certification.

Since the passing of the Mental Treatment Act in 1930 it has been noticed that a number of patients who have been discharged recovered from hospital seek readmission as voluntary patients within a comparatively short time of their discharge.

The nature of the action of insulin in producing cure in cases of schizophrenia is still quite obscure. One of the most striking features of insulin hypoglycaemia is the occurrence of phenomena pointing to disturbance of the autonomic nervous system, and many authors on this subject have expressed the belief that insulin produces cure by virtue of its action on the autonomic nervous system. There is, however, extensive contradiction in the literature as to what actually are the changes which take place in autonomic functions during hypoglycaemia. Some authors say that hypoglycaemia produces a generalized sympathetic stimulation, some say a generalized parasympathetic activity and others that there is dissociation of action of the two systems. Sakel (1) appears to believe that hypoglycaemia produces a vagotonia which underlies the curative effects of his treatment; Hadorn (2), that small doses of insulin stimulate the vagus, and large doses cause a primary secretion of adrenaline; Beno (3), that changes on the vegetative system cannot be sufficient to allow a reasonable understanding of the results; Pfister (4), that hypoglycaemia produces beneficial effects in schizophrenia because it damps the sympathetic; Wespi (5), that dissociation appears to prevail in the autonomic regulation; Gellhorn (6), that the treatment is successful because it leads to excitation of the sympathetico-adrenal apparatus through hypoglycaemia of the brain; and lastly, Heilbrunn (7), that his experiments are in favour of a sympatheticotonia.

During the course of research into an improved method of the Meinicke Klärungs Reaction (Ford Robertson, W. M., and Colquhoun, D. B., 1939) certain undesirable zone reactions occurred. This paper deals with some of the factors responsible for such non-specific precipitations.

There has been an extensive literature on accidents occurring during cardiazol treatment, and since the largely conflicting pathogenic view-points have been discussed in recent reviews (Gross and Gross-May, 1939; Kennedy, 1940; Wyllie, 1940), there is no need for their detailed enumeration. Gross and Gross-May, whose paper was unfortunately not available to us in the original, recently summed up the more important causes of accidents, grouping them into mechanical disorders, particularly of the osseous, tendinous and muscular system; disturbances of the vascular system—arrhythmia, auricular fibrillation, syncope and vascular spasm due to the specific action of cardiazol; and finally, respiratory disturbances—arrest of respiration, pulmonary embolism, and abscess due to thrombophlebitis at the site of injection.