Shortly before the end of the last century, Eijkman observed that fowl receiving a diet of polished rice developed a disease which he believed to be of the same nature as human beri-beri. It was subsequently shown that this condition in fowl (polyneuritis gallinarum), and beri-beri in man, could both be cured by the addition to the diet of rice polishings or an extract prepared from them. In 1911, Funk obtained from rice polishings a crystalline substance capable of preventing or curing beri-beri, which he named “vitamine” in view of its evident importance to life, and in the erroneous belief that it had the chemical structure of an amine. Four years later, McCollum and Davis demonstrated that at least two such dietary factors were necessary for growth in rats—“fat-soluble A” and “water-soluble B”. Before long it was recognized that the latter factor had the properties of the antineuritic “vitamine“, and a number of similar organic compounds were discovered, which were essential constituents of the diet in minute quantities, and for which the general term “vitamin”, was agreed upon. For several years it was assumed that water-soluble vitamin B (contained in yeast, rice polish, liver, etc.) was a single entity, but in 1919 Mitchell noted that certain vegetables rich in the antineuritic principle had little power to promote growth, and in 1926 two fractions were distinguished, each essential for growth—thermolabile vitamin B1, containing the antineuritic principle (thiamin), and thermostable vitamin B2.

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.

Parnell (1951) reported that 76 men undergraduates at Oxford had lost a full term's residence on account of psychological ill health in the period of three years from 1 January, 1947 to 31 December, 1949. Psychological ill health had caused 52·5 per cent. of all prolonged absence through illness, a fact which emphasized the need for more detailed study of the causes and possibility of prevention of psychological disturbance. As an indication of minimal current prevalence of such disturbance, it may be reported that 59 Oxford students in need of psychiatric help were referred by their general practitioners to the Warneford and Park Hospitals in twelve months from 1 April, 1953 to 31 March, 1954: these figures take no account of the numbers treated elsewhere; but the evidence as a whole shows that, as found in 1951, mental upset is still the most important cause of ill health in Oxford students.

Information derived from a comparison of somatotype, electroencephalographic, psychological and psychiatric findings upon patients and healthy controls is summarized in this paper. It shows that, despite a probable bias in the controls, significant differences can be detected between the two samples. Some of these differences were sufficiently marked to form the basis for a simple heuristic method of detecting vulnerability.

Psychiatry is handicapped in the task of evaluating new methods of treatment because it has had to tackle the problems presented by early and mild cases without modern psychometric methods. There is clearly something wrong when the spontaneous remission rate in schizophrenia can be reported by the New York State Hospitals as 59 per cent. (1944) at a time when the equivalent figure in Kent (Monro, 1950) was 24 per cent. The practical impact of this failure to define terms is that the majority of articles describing the results of new treatments lose most of their force. This happens most obviously when the cases considered are presented simply in diagnostic categories, for example, as x schizophrenics or y hysterics. The trouble can be lessened by giving more clinical detail, but seldom can enough diagnostic and prognostic information be given to enable the reader to arrive at a proper evaluation of the issues presented. New descriptive techniques are therefore an urgent practical necessity, as well as being theoretically desirable.

The following facts concerning West African witchcraft were observed and recorded by the present writer while working as an ethnologist in the Gold Coast. The writer had not, at that time, any psychiatric experience, but has since worked in British mental hospitals long enough for the facts to invest themselves with psychiatric significance.

Cerebral electrostimulation of subconvulsive intensity causes a pronounced increase in the concentration of adrenaline-like substances in the blood (Weil-Malherbe and Bone, 1952b). This effect is presumed to be due to a central action of the current, since these investigators were unable to demonstrate any rise when both electrodes were placed on the same side of the head. The current which was used in these experiments consisted of brief rectangular impulses with a repetition rate of 100 pulses per second (Montagu, 1953). Recently, while experimenting with shorter pulses at correspondingly higher repetition rates, the author observed that the motor response diminished as the frequency was raised, the peak and average current levels remaining constant. This effect, which appeared to be due to the progressive abbreviation of the pulses to the point at which they ceased to be effective motor stimuli, suggested that these conditions might be advantageous in electrostimulation therapy, provided that the autonomic effects were not equally impaired. Firstly, however, it was necessary to determine whether the diminution in the motor effects at the higher frequencies was part of a generalized reduction in the efficiency of cerebral stimulation or whether there was a differential response. Accordingly, with the assistance of Dr. Weil-Malherbe, the blood adrenaline level has been studied in relation to the different conditions of stimulation. The results of this investigation are contained in the present report.

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).

One of the important schizophrenic symptoms listed by Bleuler (1950) is a disturbance in attention. Bleuler viewed the attention disturbance as a complex phenomenon which was also related to disturbances in thinking and affect, and possibly to individual emotional complexes.

It is evident from many reports published in the last four years that psychological changes can occur during the treatment of physical illness by Cortisone and corticotrophin (A.C.T.H.). There is no doubt, too, that similar mental symptoms have been occasioned by giving either of these agents in therapeutic doses. It is perhaps for this reason that most writers have not distinguished between them in this respect. Thus, the mild mood changes that often occur, and the relatively rare psychotic reactions are usually spoken of as complications of A.C.T.H. or Cortisone therapy. This implies that, in the individual case, these substances would be equivalent in their influence on the mental state; yet there are grounds for suspecting otherwise. The aetiology of these psychological reactions remains obscure, so that any evidence which serves to differentiate the psychiatric side-effects of the two drugs would be of interest.

The use of chlorpromazine is now firmly established in psychiatry (Delay et al., 1952; Arnold et al., 1953; Staehelin and Kielholtz, 1953; Anton-Stephens, 1954; Elkes and Elkes, 1954; Charatan, 1954). A hyperglycaemic effect in man has already been reported (Dobkin et al., 1954), and might be of importance if, for example, in schizophrenia, chlorpromazine was combined with insulin coma treatment. The following investigation was carried out to study the effect of chlorpromazine on glucose tolerance.

Chlorpromazine hydrochloride (Largactil) introduced by Laborit (1952) has aroused considerable interest on account of its varied pharmacodynamic actions and clinical reports drawing attention to its possible use in anaesthesia, general medicine and psychiatry.

Chemically related to certain antihistamine drugs, it has little antihistaminic activity itself but has diverse effects on the nervous system. It is a neural depressant with central and peripheral action, vagolytic and sympatholytic properties. (Chauchard, 1952; Courvoisier, 1953; Sigwald and Boutier, 1953; Staehelin and Kielholz, 1953; Lehrman and Hanrahan, 1954; Anton-Stephens, 1954; Winkelman, 1954; Garmany, 1954; and Elkes and Elkes, 1954.)

Enthusiastic claims have been made regarding the therapeutic value of chlorpromazine in a wide variety of psychiatric disorders; many of these have failed to carry conviction, as most of the reports are based on mixed groups with an insufficient number of patients in each diagnostic category to justify definite conclusions and also because controlled procedures were rarely used.

We therefore decided to confine our investigation to one type of psychiatric disorder and chose anxiety states, since the reported pharmacodynamic actions of the drug suggested that it might be of value in the treatment of states of anxiety and tension. The total group studied consists of 150 patients all of whom are treated as out-patients.

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.

The recognition of a well-established psychosis due to arteriosclerotic or senile brain changes rarely presents any difficulty. However, increasing numbers of elderly people are seen with affective, paranoid, or neurotic manifestations, and it is sometimes very difficult to decide whether their symptoms present prodromata of an organic psychosis, or whether in the absence of degenerative brain disease they are occasioned by a variety of endogenous and environmental causes leading to a “functional” psychiatric illness.

Several studies have been undertaken in which the “dark vision” of normal and neurotic groups has been compared (see (5) for references). As a result of these researches it appears that neurotic patients tend to have inferior performances to normal subjects on tests of “dark vision”. The term “dark vision” is, however, a very general one, covering all aspects of visual functioning at brightness levels below about 0 · 01 candle per square foot (13). Clearly we need to know more precisely which aspects of dark vision are impaired in neurotics, the extent of the impairment, the conditions under which it occurs, etc., if we are to go beyond fairly crude descriptive statements about differences between normal and neurotic groups to an understanding of the processes involved.

A number of drugs have been employed in an attempt to increase the mental capacity of oligophrenics. The effect of thiamine on learning demonstrated by Harrell (1943, 1946) led Rudolf (1949, 1950) to use this vitamin in the treatment of oligophrenia. Similarly, the early studies of Zimmermann and Ross (1944) on glutamic acid resulted in a large number of papers on its debatable effect in feeblemindedness (Zimmermann, Burgomeister and Putnam, 1946, 1947, 1948; McCulloch, 1950; Ellson, Fuller and Urmston, 1950; Quinn and Durling, 1950; Lafon, Faure and Bascou, 1952; Oldfelt, 1952). The results of celastrus paniculata on mental defectives have been described by us elsewhere (Morris, MacGillivray and Mathieson, 1953, 1954).

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.

In determining the diagnostic value of psychological tests the usual external criterion is the psychiatric diagnosis. This criterion has suffered a steady decline in prestige among both psychiatrists and psychologists. The following remarks by Noyes (1953) would be endorsed by many psychiatrists: “The principal value of classification is not in the categorizing of a disease entity but in quickly eliminating those considerations which will be least useful in understanding the patient and in directing attention to those which are likely to be relevant. Except in organic disorders a classificatory diagnosis is less important than a psychodynamic study of the personality. The psychiatrist should be interested in processes, not in labels … we should endeavour not so much to fit the symptoms into a classificatory scheme as to understand the sick person in terms of his life experience.”

Synaesthesia is defined by Vernon (1937) as a phenomenon in which “a stimulus presented in one mode seems to call up imagery of another mode as readily as that of its own”. The discovery of synaesthesia has sometimes been wrongly attributed to Galton. Galton (1883) certainly describes instances, but reports on earlier descriptions, for example those published in 1881 by Bleuler and Lehmann.

Experiments with animals have shown that electrostimulation of brain tissue is followed by a number of biochemical changes in the brain. The information obtainable is limited since there are only comparitively few reports about investigations in this field (4).

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.