The Founder of this lecture series was described with consummate skill by Professor Aubrey Lewis in the Twenty-fifth Maudsley Lecture, before this Association. Henry Maudsley was a clinician who turned again and again to the problem I shall approach today. He even wrote a monograph under the daring title of “The Physiology and Pathology of the Mind”.

The hyperventilation syndrome is the name given to a distinctive group of symptoms and signs which are caused by an increase in the depth and rate of breathing. This abnormal breathing is nearly always the result of emotional stress.

This is an account of a model psychosis (6) produced by eating the seed of a tropical American plant which is known in Mexico as ololiuqui. It is only quite recently that Schultes (16) has made order from chaos in the matter of the identity of a climbing vine called Rivea corymbosa. I was introduced to ololiuqui by Mr. Leslie LeCron during a visit to Los Angeles in which he showed me Taylor's (22) article where he compares it with the peyote. Mr. LeCron discovered that seeds of Rivea corymbosa could be obtained from Dr. I. D. Clement, Director of the Atkins Gardens and Research Laboratory of Harvard University. I am indebted to Dr. Clement for sending me a supply of the seeds which would otherwise have been very difficult to obtain. It is reassuring for the investigator to know that the substances with which he is experimenting have been collected by skilled scientists who exercise meticulous care, for medical and pharmacological investigators have very often suffered from improper or imperfect botanical determination.

Osmond and Smythies (1952) have given reasons for reviving the view originally put forward by Bleuler (1950) that schizophrenia is essentially a disorder of metabolism, and have suggested that some substance chemically related to mescaline might be the causative agent. Hoffer, Osmond and Smythies (1954) have begun an investigation of this hypothesis and have found that adrenochrome, an oxidation product of adrenaline which is probably a normal intermediate metabolite, has active hallucinogenic properties. These authors do not regard adrenochrome as being unquestionably the toxic agent in schizophrenia, but suggest that it or some closely related substance, having the indole ring and derived from adrenaline, is involved. They also advance the opinion that the metabolic fault consists of an overproduction of adrenochrome or similar substances. Such a view necessarily implies either overproduction of adrenaline or a blocking of one or more of the paths of adrenaline detoxification in the body which do not lead through adrenochrome. As adrenaline is derived from tyrosine the hypothesis is essentially one of abnormal tyrosine metabolism. From this hypothesis certain deductions can be made.

In making an investigation of Huntington's Chorea in the State of Victoria, we have, so far, been able to collect 150 indisputable cases of this disease, and others. This figure includes 83 deceased, and 57 living. Out of a total of 74, who were certified to mental hospitals, 26 are still either in hospital or on trial leave. This represents ·34 per cent. of the total present mental hospital population. As regards sex distribution, our figures indicate that there were 68 females as compared with 72 males.

Isonicotinyl Hydrazide or Isoniazid has for some years now been used in conjunction with other compounds in the treatment of pulmonary tuberculosis. During this treatment certain workers (Robitzek et al., 1952) noted the development of a state of euphoria in their patients. Since Isoniazid was known to exert toxic effects on nervous tissue (Gammen et al., 1953) the hypothesis was made that the substance might be capable of producing an elevation of mood by direct action on the central nervous system. Acting on this hypothesis, Salzer and Lurie (1953) treated a group of patients suffering from various depressive conditions with Isoniazid given orally in the dosage of 50 mgm. t.d.s. for one week. If no toxic effects occurred the dosage was raised to 100 mgm. t.d.s. for a further two weeks, while in a few cases only higher doses were given. These workers maintained this level of dosage in order to avoid the advent of toxic side effects. Their results, which will be discussed later in this paper, led them to the conclusion that isoniazid had a specific therapeutic effect upon certain depressive disorders.

The object of this study, arising out of the work mentioned, was to carry out an initial survey of the effects of isoniazid on the affective component of various depressive states. If any demonstrable therapeutic action had been noted a larger, controlled, and more systematic study would have been undertaken but in view of the results obtained this further project has now been abandoned.

Raoul Leroy was the first alienist to take a scientific interest in diminutive hallucinations which he labelled “Lilliputian” (1909) and they can best be described in his own words (1922).

During the past five years a number of reports have acclaimed Subconvulsive Electrostimulation as a therapeutic measure for the relief of states of anxiety and tension. In general, these accounts have proved unconvincing, since the authors have seldom provided either controls or even details of their results. The report of Hargrove, Bennett and Ford (1953) has been the only exception to both of these criticisms—and the only adverse account. The present investigation was therefore conducted as a “blind” trial in order to provide an unbiassed evaluation of the subject. The series comprised 100 patients, half of whom received the electrical treatment while the other half were subjected to a control procedure. Objective evidence was furnished by psychometric tests. An autonomic test of reputed prognostic significance, and a follow-up study, were also included.

Sleep as a method of controlling mental derangements dates to antiquity. According to Celsus sleep restores mental equilibrium: “but certainly for all so affected sleep is both difficult and especially necessary; for under it many get well …” (13). Griesinger in 1861 was the first to use chloroform as a sleep-inducing agent in mania and melancholia (21). The advent of bromides and barbiturates enhanced further investigation, and early in this century sleep treatment was relatively well systematized by Wolfin 1901 (40), Trend in 1903 (39), and by Kläsi in 1922 (25). This paper will not attempt to review the literature on sleep, for these findings have been outlined in papers by Palmer (32, 33), Baer (7), Ey (18), and recently in a documented book by Angel (2). The purpose of this paper is to present (1) a method of prolonged sleep treatment using the new inhibitory substance chlorpromazine (Largactil), in combination with different barbiturates in an attempt to provoke a sleep pattern as similar as possible to normal sleep, in contrast to deep unconsciousness advocated previously (14, 32); (2) to discuss underlying theories of sleep treatment, and propose some new formulations; (3) to suggest future use and investigation of the treatment; and (4) to bring to the attention of American psychiatrists a treatment which holds an eminent position in Europe, particularly in the U.S.S.R. where sleep therapy appears to be the only officially accepted form of treatment in mental illnesses.

This paper describes treatment with cortisone and A.C.T.H. of two patients in whom Alzheimer's Disease (A.D.) had been confirmed histologically by cerebral biopsy.

A.D. is a progressive dementia which usually occurs between the ages of 40 and 60 years, and there is no known specific treatment. Intellectual deterioration, which progresses insidiously over a period of 2–10 years, leads to gross dementia, and the inevitable problems of care and supervision often necessitate removal to an institution. Histologically the disease is characterized by atrophy of cortical nerve cells and the presence within the cortex of argentophile plaques which are demonstrable by the silver impregnation techniques of Bielschowsky or von Braunmühl (see Fig. 1); these plaques have a mixed granular and fibrillary structure. The same silver methods also show irregular thickening and disorientation of the nerve cell fibrils, which form “tangles” and “loops” (see Fig. 2). Identical plaques and neurofibrillary changes are also seen in senile dementia, the term “senile plaque” being used in both diseases.

In this paper, the term Acute Infantile Cerebral Diplegia has been used to denote a group of cases in which a spastic paralysis, affecting principally the lower limbs, develops suddenly in infancy or childhood. The course of the disease is remarkably uniform in the majority of cases, thereby suggesting a common pathogenesis.

It is natural to assume that because a psychosis occurs during the process of childbearing the two events are therefore necessarily associated, but the evidence is conflicting and the relationship between them has not been established with certainty. In fact no immediate dramatic cause has yet been demonstrated that would account for such mental breakdowns, and it would be surprising if it had, for the great majority of psychoses not related to maternity show no simple sequence of cause and effect.

Yet it would be wrong to dismiss without further examination an occasion so important in the life of the mother as childbirth as of no aetiological consequence. In the types of psychosis under consideration the clinical onset had often been a sudden and disturbing event, just at that particular time in the patient's life when she was confronted with the responsibility of motherhood. Further examination of the patient's history however often revealed previous evidence of emotional disturbance, or of instability in other members of her family.

Chlorpromazine hydrochloride (3-chloro-10 (3′-dimethylamino-propyl)-phenothiazine) or “largactil” is being widely tried out as a form of therapy in psychiatric disorders. Papers have appeared describing its use in comparatively severe conditions encountered in in-patient mental hospital practice (e.g. Anton-Stephens, 1954) and in psychoneurotics (e.g. Garmany, May and Folkson, 1954). In the psychoneurotic group in particular, the drug is reported to be helpful in reducing tension and diminishing pre-occupation with worries, fears, and concomitant symptoms. These two properties—the reduction of tension and the production of a feeling of relative indifference to distressing stimuli—were amongst those originally attributed to chlorpromazine by Sigwald and Bouttier (1953) and, of course, they approximate to the characteristic changes resulting from prefrontal leucotomy (Partridge, 1950). The effects of this operative procedure have been extensively studied in relationship to such factors as the previous personality of the patient and the duration of the illness involved (e.g. Baker and Minski, 1951) and it was considered that it might be of value to investigate similar factors in patients treated with chlorpromazine. It is true that prefrontal leucotomy entails structural damage as a result of which the previous personality, for example, may be expected to have a significant bearing on the therapeutic outcome, but even with patients treated by chlorpromazine the ultimate result may depend, at least to some extent, on the inherent make-up of the individual or the symptom-complex from which he is suffering. It was in order to study the relationship between factors of this nature and chlorpromazine treatment that the following investigation was undertaken.

In connection with a demonstration programme of comprehensive psychiatric care for hospitalized schizophrenic patients, it was necessary to develop a rapid and effective method for rating patients' ward adjustment and social behaviour. The scale, entitled the Albany Behavioural Rating Scale (ABRS), and its validation, are described in this report. The nature of the problem required that the scale be readable, easily completed and scored, and suitable for use by nursing and rehabilitation personnel (OT, CT, Music Therapist, etc.). Further requirements included adequate scoring reliability and validity, as well as amenability to quantification.

Various rating scales have been described in the psychiatric literature, but these did not meet our needs. Some were too cumbersome and time-consuming. Others required individual psychiatric interview. Frequently they demanded high literacy of the rater. Certain scales are indeed useful for special purposes, as for example the MSRPP (Lorr, 1953) which can be employed with confidence as an aid to psychiatric classification. Lucero and Meyer (1951) have discussed the requirements of an adequate rating scale.

Sodium amytal has long been regarded as a physiologically inhibiting drug. It is widely used in clinical practice as a sedative and sleep-producing drug, although all of its precise pharmacological effects are not definitely established. It has also been suggested that sodium amytal produces an increase in extra-version, as manifest by an increase in communicativeness, etc. Thus Lindemann (1932) found that after receiving amytal, normal subjects report feeling of increased well-being, co-operativeness, serenity and friendship. Sodium amytal is also used for the reduction of manifest anxiety. Sargant and Slater (1954) cite many examples of its use for this purpose with neurotic subjects; they describe it as useful for “deconditioning to situations likely to produce anxiety”. Masserman (1938) reports that amytal apparently reduces the sympathetic activity in cats which normally results from faradic stimulation from the hypothalamus. It has also been shown to abolish conditioned fear responses in kittens (Bailey and Miller, 1952).

The literature related to conditioning is enormous. Hilgard and Marquis (1940) alone have a 973 item reference list at the end of their book. It has been established that anxiety neurotics or anxious subjects condition better than normals (e.g. Welch and Kubis, 1947a, 1947b; Taylor, 1951; Spence and Taylor, 1953; Spence and Farber, 1953). In the terminology of Eysenck (1952, 1953), in which introversion–extraversion and neuroticism are two orthogonal dimensions, anxiety neurotics are part of the groups known as Dysthymics, i.e. they have high scores on both the introversion end of the introversion–extraversion dimension and on the dimension of neuroticism. On the other hand hysterics and psychopaths have been shown to have high scores on the extraversion end of the introversion–extraversion dimension and on the dimension of neuroticism. Figure 1 will make this clear.

It has been recognized for at least 150 years that the organization of wards in public institutions often “results in a lack of adequate attention, provides an unnatural environment and promotes neglect, abuse, injuries and confusion”, Noyes (1953). The atmosphere of the mental hospital back-ward, so different from that existing in the patient's home, creates a social, psychological and physiological “vacuum” and is particularly unfavourable to the long staying schizophrenic patient, who, as a result shows a progressive deterioration in habits and social relationships.

An early remedy practised at the York Retreat (Samuel Tuke, 1813) was that the nurses, having gained the patients' confidence, should attempt “to arrest their attention, and fix it on objects opposite to their illusions; to call into action as much as possible, every remaining power and principle of the mind; and to remember that, in the wreck of the intellect, the affections not unfrequently survive.”

As an approach to the problem of schizophrenia it is proposed to compare the effects and after-effects of severe hypoglycaemia due mainly to islet-cell adenoma of the pancreas in otherwise healthy people with the effects and after-effects of severe hypoglycaemia therapeutically induced in schizophrenics.

The difficulties are plain. Personal experience of patients with functioning islet-cell adenoma is limited almost always to a few cases, whereas average experience of insulin coma treatment covers some hundreds of cases; moreover, there is little overlap of experience except in the post-mortem room or in the laboratory for morbid histology. During insulin treatment there is constant supervision by a trained staff, medical and nursing, so that serious developments can be met by immediate intravenous sugar and investigations are continual; with adenomata there is no observation until, perhaps, a general practitioner is called in about alarming symptoms of one kind or another and sometimes months or even years elapse before a patient gets into hospital, where the intensity of observation and even more so of investigation may exceed that available in mental hospitals. Insulin coma treatment has a more or less standard aim, to produce coma of increasing duration up to a maximum of something like an hour which is then repeated thirty times or more; dosage is built up with the greatest care. Adenomata produce conditions varying from the hardly serious to the fatal under the influence of an insulin dosage which is quite unknown.

This comparison is based chiefly on an analysis of 290 serial courses of insulin coma treatment given to schizophrenic patients at Holloway Sanatorium during the four years 1950 to 1953 inclusive, and on the 258 cases of islet-cell adenoma reported by Crain and Thorn (1949) and the 398 cases, all that could be traced up to that date and including the Crain and Thorn cases, analysed by Howard, Moss and Rhoads (1950). Many separate papers have been consulted for more detailed approaches and for extra information, although of course those published before 1950 were included in the reviews already mentioned. Despite the difficulties of this comparison, it can be shown that the similarities between the two groups follow expectation and are very strong indeed, so that the differences which emerge have at least possible significance.

The last thirty years have witnessed the rise and fall of many theories and therapies on a supposed relationship between psychiatry and endocrinology, and perhaps the time is now ripe to weigh the evidence and attempt to draw at least tentative conclusions. A clear picture of an existing situation not only often leads to improved understanding but also to greater clarity of purpose.

It has long seemed apparent to workers in the child guidance field that many of their patients show evidence of longstanding emotional disturbance; either the symptoms now complained of have been present for many years, or there has been a history of symptoms earlier on which have disappeared only to be replaced by the existing ones. Some of these patients whose present condition may be almost intractable, might have been helped had they been treated at an earlier date, while recent work by Bowlby (1951) and others has emphasized how important are security and satisfactory emotional relationships in the early years for the establishment of a stable personality. Thus it appears that any prophylactic approach, aimed at reducing the incidence of emotional disturbance in older children, and it is hoped ultimately in adults, may need to be made very early in life.

Little has been published, apart from accounts of individual patients, of work on any series of very young children who were psychiatrically disturbed, particularly from a prophylactic point of view. Joseph (1948) has described some of the patients she has seen in a child guidance clinic attached to a child welfare centre, and Gillespie (1954) has compared the symptomatology of a series of pre-school children treated at Infant Welfare Centres with the preschool histories of older children treated in a child guidance clinic. She points out that the type of problem dealt with in the under-fives was seen in a high proportion of the earlier histories of those who needed treatment at a later age. The importance of early treatment for parents in the prevention of serious disturbance in the children has been emphasized by Fries (1946) by Jacobs (1949) and on a community scale by Caplan (1951). His experience in Infant Welfare Centres in Israel over a number of years has led him to concentrate on the treatment of cases where abnormal symptoms were not yet manifest, but where pathogenic relationships of the parents to the child were such that he felt that emotional difficulties in the child might later develop. In this country such a prophylactic approach is relatively unexplored, although the possibility of preventing mental ill health in children is one which has interested public health authorities for some time.

“No man is an iland, intire of itselfe; every man is a peece of the Continent, a part of the Maine; if a Clod bee washed away by the Sea, Europe is the lesse, as well as if a Promontorie were, as well as if a Mannor of thy friends or of thine owne were: any mans death diminishes me, because I am involved in Mankinde. And therefore never send to know for whom the bell tolls; it tolls for thee.”—John Donne.