Biological rhythms exist in a rich variety and almost bewildering profusion to attend and equilibrate the physiology of man. Such dynamic phasic activity appears not only to be intimately concerned with the phenomenology of life and biological processes in general, but is also to be found in purely chemical systems (Hedges and Meyers, 1926). Modalities of the periodicities associated with life can be divided into those external to the organism—including diurnal and climatic variation, sun-spot activity, etc., and into those inherent within the individual such as the respiratory and cardiac rhythms, the menstrual cycle, sleep and awakening. Only less well marked are certain psychological periodicities such as “cyclothymic “variations in mood and personality. In the course of the present century much painstaking research has attempted to link external with internal rhythmic activities, significant correlations being adduced between seasonal variation and, for example, the incidence of psychiatric disorder (Huntington, 1915), immunity from disease (Spencer and Melroy, 1943, Webster, 1944), temperament and behaviour (Petersen, 1934-36; Mills, 1942), and an impressive array of biochemical and physiological variables ranging from blood pH, lactic acid and protein to breath-holding time, plethysmography, tests of hand strength and fatigability, dark adaptation time and various tests of urinary function (Petersen, 1947).

The assessment of pain perception is a subject of great importance from both the practical and the theoretical aspect. The increasing use of curare-like drugs as muscular relaxants and basal anaesthetics (Mushin, 1951), and in conjunction with electro-convulsant therapy (E.C.T.), has made the orthodox tests for depth of anaesthesia unreliable because they depend on the activity of voluntary muscle. E.C.T. itself (Morgan, 1950) and industrial electrical accidents (Hume, 1935) have given rise to unusual states of consciousness which cannot be fully understood until more is known about the way in which electric shock affects the central nervous system. On the theoretical side many explanations of the essential features of a state of consciousness have been given, but none of them accounts completely for all the observed phenomena; investigations designed to improve methods of assessment should provide useful information which, when correlated with that from other fields, may ultimately lead to a better understanding of the conscious state. The object of the experiments described in this paper has been the development of tests which will indicate the level of consciousness, and in particular the appreciation of pain, when the voluntary muscles are paralysed.

Somatic disturbances in schizophrenia include metabolic, circulatory and endocrine changes frequently associated with disorders of the pituitary gland and adrenal cortex. Depression of the metabolic rate is often severe (Hoskins, 1932), the systolic blood-pressure is sometimes as low as 80 mm. Hg (Hoskins, 1934; Rheingold, 1939; Shattock, 1950), and the pulse pressure only a few millimetres. Peripheral vascular deficiency and atrophy of the tissues (Bleuler, 1920; Mapother, 1924; Minski, 1937; Shattock, 1950), asthenia and various cutaneous changes are common; amenorrhoea is almost the rule.

It is remarkable that these disturbances are reversible, and that they are relieved or greatly alleviated during mental remission. Physical health is restored during a spontaneous remission, and a gradual improvement can be observed during a course of insulin comas. Sometimes a dramatic recovery follows electroconvulsion when this initiates a mental remission; somatic improvement is then rapid and the vascular deficiency may be relieved within a few hours (Shattock, 1950). Unfortunately these remissions are often brief, and as relapses become more frequent after repeated treatment, physical and mental deterioration may be noticeable a few days after the initial improvement. The point of interest is a concordance of physical and mental changes, and not the therapeutic value of E.C.T. used as an adjunct to insulin treatment or as a means of moderating extreme restlessness in chronic patients.

It has been shown by a number of workers that in a large proportion of cases the E.E.G.s of schizophrenic patients are abnormal. This paper is an attempt to increase our knowledge of the hereditary background of schizophrenia by recording the E.E.G.s not only of those suffering from the disease but also those of their near relatives.

The E.E.Gs. of schizophrenic patients have been studied by a number of workers, notably Davis and Davis (1939). P. Davis (1939, 1940, 1942) attempted a classification of schizophrenic records, defining the main types of pattern. Gibbs et al. (1938), Jasper et at. (1939), and, more recently, Hill (1946), have noted the presence of epileptic activity in the E.E.G.s of catatonic schizophrenics.

Pain and fatigue, subjectively experienced, are two of the commonest complaints made by patients suffering from a variety of psychoneurotic and psychotic disorders. Neither phenomenon has so far been adequately studied with the available objective techniques, and the present paper embodies results of preliminary experimental investigations of fatigue and pain tolerance, together with a review of some of the clinical aspects of the problem.

In psychiatric disorders pain rarely produces overt signs which allow the observer to judge its severity, and the excruciating pain complained of by some patients appears to be accompanied by much less emotional reaction than, for example, the pain experienced by the normal individual after a burn, a crushed finger, or an abdominal catastrophe.

The intelligence, as measured by standard tests, ceases growing after about 14 or 16 years of age, and slowly decreases from about 25 or 30 years of age (Wechsler, 1945). The sex glands are developing as the intelligence ceases to develop.

In view of these observations, consideration was given to the possibility that the defective developed mentally to a degree below the normal because too great a quantity of the appropriate sex hormones was circulating in the blood stream. In consequence, the opposite hormone was administered, stilboestral being given to males and pernandren to females.

It is now well recognized that many of the syndromes previously described as pellagra, such as nutritional retrobulbar neuropathy, the ataxic, and burning feet syndromes, may occur as isolated manifestations of nutritional deficiency. The term “pellagra,” as it is often used, is no more than a generic title embracing a wide variety of nutritional disorders. The clinical status of the individual deficiency syndromes has been elucidated of late years in America (Spies et al., 1939; Harris, 1941), and with particular regard to the neurological disorders, in groups of prisoners of war in the Far East (Denny Brown, 1947) and Middle East (Spillane, 1947). The majority of the pathological studies of pellagra were completed in the era before advancing biochemical knowledge provided the impetus to further these clinical studies, and this is reflected in the great diversity of neuropathological changes described as “pellagrous.” The extensive literature contains many excellent studies of cases dying from malnutrition, and it now seems possible to attempt a correlation between the pathological findings and the more recently described individual syndromes. A review, therefore, of the neuropathological changes encountered in “pellagra” might be not untimely.

The evidence for somatological differences between various types of schizophrenia and its different stages of severity or chronicity is still scanty and often contradictory. The present investigation mainly concerns itself with endocrinological factors. Kraepelin, already, suggested disturbances in the endocrine system. The incidence of schizophrenia in different age-groups, especially its steep rise at puberty, reaching its peak at 20 in men and 25 in women and the rapid decline of its occurrence after these ages (Haas, 1938), has for a long time pointed to the sex steroids as an important factor in the pathology of this disorder. Hemphill et al. (1944, 1945, 1948) found an atrophy of the testes in many cases of schizophrenia, and considered the severity of the testicular change to be proportional to the severity of the psychosis. They suggest that the testicular lesions are not the cause of schizophrenia, but probably effects of the “pathogenic process” and related to hypothalamic or pituitary function. In confirmation of these findings Hoskins and Pincus (1949) observed the output of androgen in schizophrenics to be significantly lower than in normal men. Sears (1937) made similar observations in females, and found that the blood-œstrin level of female schizophrenics was much lower than in normal women. Possibilities for primary endocrinological factors suggest themselves; the “pathogenic process” can, however, still be primarily a psychological “stress” in this new constellation or a combination of both, or the effect of another central disturbance. Some of our somatological findings can, therefore, tentatively be interpreted as related to or identical with the primary stress or others only as secondary correlates or results, though the present state of our knowledge does not yet allow a final decision as to what is primary and what only secondary. Recent evidence, on the relationship of sex hormones and insulin (Houssay, 1951) suggests that oestrogens have a “sensitizing” and androgens a “desensitizing” effect. An investigation into the insulin sensitivity in clinically different schizophrenic groups and the two sexes expressed in the amount of insulin needed to produce a hypoglycaemic coma should, therefore, throw some light on other endocrinological mechanisms.

The Colour-Form Sorting Test was described by Weigl (1927) as one of a series of investigations into the nature of the psychological deficit resulting from a cerebral lesion. The material consists of 12 pieces: four squares, coloured severally red, yellow, blue and green; four circles, similarly coloured; and four equilateral triangles, similarly coloured (Fig. 1). They are presented in a random arrangement to the patient, who is asked to group them according to any similarity he sees; and when he has sorted them according to one principle, is then asked to sort them according to another.

Other problems involving sorting were presented in Weigl's study, and have been used in a number of investigations, particularly of the effects of frontal lobe lesions. Rylander (1939) found that his group of patients with frontal lesions differed significantly from the normal controls in the number of principles found for grouping 15 objects. Halstead (1940) used 62 common objects, and also found that patients with frontal lesions tended to find fewer principles for sorting than did patients with cerebral lesions located elsewhere. Subsequently Halstead and Settlage (1943) developed a mechanized grouping test, using geometrical figures: three patients, with frontal lesions, and one with a left occipital lesion, made many more errors than did the normal controls; while a patient with a right occipital lobectomy and one with a left parietotemporal lesion performed normally in this respect. Finally Halstead (1947) found that, of his group of ‘indicators” of cerebral damage, a similar test (No. 2) not only differentiated reliably the patients with cerebral lesions from the normal controls, but also gave a significantly higher error score with cases of frontal lesion.

Goldstein and Scheerer (1941) included Weigl's test in their experimental study of abstract and concrete behaviour; and Trist and Trist (1943) and Brody (1943) noted impairment on this test in cases of general paralysis and the presenile dementias.

Flexibility in adjustment on the part of the interviewer is commonly regarded as one of the main qualifications for good interviewing and part of an interviewer's skill. The high estimation of the spontaneity of the interviewing situation, which has been one of the main reasons why the interview as a technique has retained its popularity against more standardized and reliable methods, rests largely on the presupposition that skilled interviewers can adjust their own behaviour and steer the interviewing situation freely so as to obtain optimum rapport and maximum information. Thus Oldfield (5) considers changes of topic, attitute and tempo of great significance for the conduct of the interview. He particularly stresses the importance of changes of tempo; pauses in the conversation, he says, if “badly chosen may easily break the trend of the relationship which is being built up. On the other hand, if well chosen, they may contribute markedly to the success of the interview.” No evidence, however, exists to show to what extent skilled interviewers actually are free to adjust themselves to any particular interviewing task or which aspects of their interviewing behaviour are more subject to adjustment than others.

Research was carried out by a small unit in the York Clinic at Guy's Hospital into the possible connection between migraine attacks and the patient's emotional life. The hypothesis was that migraine was a product of stress and should, therefore, respond to psychotherapy directed towards helping the patient to deal with his emotional problems in a more adequate way. The clinical aspects of the investigation and therapy are described in full elsewhere (2, 3). Evidence was produced to support the view that migraine is a stress disorder. Contact was kept with all the patients for a period ranging from 2 months to 2 ½ years. In a series of 20 patients eight patients were much improved by therapy, ten improved and two remained unchanged. This paper presents the results of some of the psychological tests which were applied to those 20 patients.

When electroshock is given, there is generally a rise of blood-pressure for a time. It is therefore stated in various text-books that the treatment is contra-indicated in cases of hypertension. Even premedication with thiopentone and curare does not always succeed in lowering the pressure to a safe level. It is also known that the initial rise in pressure may be followed by a subsequent compensatory fall, so that any drug which prevents fluctuations of arterial tension is likely to be of value. Etamon [tetra-ethyl ammonium chloride (T.E.A.C.)] lowers the blood-pressure by acting on the synapses of the sympathetic nervous system.

Many hospitals have found that electronarcosis is a valuable adjunct to treatment, as it is frequently successful when simple electroshock has failed. On many older patients, however, in whom this treatment is especially useful, the rise of blood-pressure can be very marked; and even forward placement of the electrodes does not always avoid this complication.

At the West London Hospital it was therefore decided to try out the effect of Etamon (Burroughs Wellcome). The bromide salt has the same effect. This drug has been used to lower the blood-pressure in hypertensive states, but there are certain disadvantages in its prolonged use for this purpose. Its administration, however, to combat a temporary rise of blood-pressure lasting 20 to 30 minutes is without any ill effects at all.

A study of the effects of E.C.T. on mental efficiency and retentivity has already been published (Hetherington, 1952). The present paper reports the effects of E.C.T. on drawings made by the same group of patients. Workers such as Prinzhorn (1922), Maclay, Guttmann and Mayer-Gross (1938), Anastasi and Foley (1943), Martin and Weir (1951) and Raven (1951) have been concerned with analysing unrestricted or “free” drawings of widely varying nature. Other workers, such as Burt (1921) and Goodenough (1926) have used restricted drawings usually of “a man” more specifically for the estimation of intelligence. Anastasi and Foley (1941) have reviewed the work done with the drawings of abnormal people, and have drawn attention to the lack of control groups, the rarity of quantitative assessments, and the danger of over-interpretation of the drawings on the part of observers. In order to meet these criticisms, patients' drawings have been compared in the present paper with those of a group of normal untreated people, assessments of the drawings being limited to quantitative measurements of area and position on the page, or to subjective judgments of consistency of style undertaken by several observers working independently.

The purpose of this paper is to outline the application to various psychiatric conditions of a test which measures peripheral capillary oxygen saturation and to discuss the significance of the findings. It is convenient to commence with a brief review of some previous work concerning the relevance of anoxaemia to psychiatry.

THE present paper offers a brief summary of work which has been published in German journals dealing with the prolongation of induced convulsions. In the course of my experimental research the following phenomena were demonstrated:

1. (1) Continuousconvulsionslastingup to oneand a half hours were produced by the administration of oxygen and adrenaline, preceded by the injection of phenyl-methyl-aminopropane.

2. (2) Prolonged convulsions of 33 minutes were produced by the intravenous injection of 2 ml. of a io per cent. metrazol solution and continuous oxygen in suffiation.

3. (3) Isolated continuous convulsive activity of the cerebellum was produced lasting 30 minutes after cessation of respiration and of all cortical electrical activity. This was achieved by continuous insuffiation of oxygen together with the injection of adrenaline and strychnine.

4. (4) Activation of a prolonged convulsion up to 11 minutes, without further electric stimulation, was effected via the thalamus by the injection of adrenaline after administration of phenyl-methyl-aminopropane and continuous oxygen in sufflation.

Mr. Gladstone, with that candour which a great Statesman can afford, once said, “Government is a rough business, and the results are most unsatisfactory.” Unfortunately no great psychiatrist has described the present state of our knowledge and treatment of schizophrenia in an equally robust phrase; but surely, “rough business and unsatisfactory results” would not be an unfair summing up ?

We have now known of this illness for nearly half a century, and yet our understanding of it is slight and our useful information scanty. This is not because we have been idle, but because our efforts have been poorly rewarded. Thousands of papers are written every decade; tens of thousands of observations are made; there is no lack of opportunity for studying patients when about one hospital bed in five in this country is occupied by a schizophrenic, yet we are still entirely ignorant of the cause of this disease. There are, it is true, numerous theories, but none is generally accepted. We have one form of treatment, deep insulin, which produces remission of symptoms in some cases and what seems to be a cure in others, but even the value of this treatment is hotly disputed. Because deep insulin is a purely empirical procedure the psychiatrist is always tempted to become preoccupied with details of technique so that he forgets, or at least becomes less aware of our fundamental ignorance.

In a previous communication (1951) it was shown that the hyperglycaemic factor described by Meduna and Vaichulis (1948) in the urine of psychotics consisted of two fractions, and that the more active and specific of these was of a protein nature. Morgan and Pilgrim (1952) have prepared concentrates of this factor from the urine of male and female schizophrenics, and have produced further evidence that it is a protein or a substance strongly bound to a protein. In normal male urine they did not find a measurable quantity of the factor.