I have been fortunate in having the opportunity of studying several of the 15 patients treated by prefrontal leucotomy in connection with the Burden Neurological Institute. I do not propose to discuss the clinical results; it is much too early as yet for any authoritative opinion to be given, and a brief review of the literature and of the early results of the first 8 cases in this series was recently published in the Lancet. It may be mentioned, however, that the results are such as to justify the cautious adoption of this operation for therapeutic purposes. Although obviously any procedure of this kind is only justifiable on therapeutic grounds, its value for psychological medicine is far more than the mere addition of another effective therapeutic method, since for the first time in history an opportunity has been presented for the study of changes in personality produced by a relatively standardized local lesion of the brain, enabling us to investigate as never before the role of the frontal lobe in normal and abnormal mental states. This investigation involves the study and correlation of both neurological and psychological data, and encounters all the difficulties inherent in such correlation.

I am only too well aware of the extremely hypothetical nature of much that follows, and of the crying need for experimental evidence to confirm or refute the view here propounded, but I believe that our knowledge of mental disorders would be immeasurably advanced could we but discover the rationale underlying our present empirical methods of therapy.

In a preliminary report (Brit. Med. Journ., 2, 310, 1940), two modifications were introduced in Sakel's technique for the insulin treatment of schizophrenia, with the primary object of continuing the treatment under wartime conditions. The first and most important of these was concerned with the saving of sugar. This simple method, by which glucose is given intravenously and is followed by a drink of potato soup as soon as the patient is awake, has already been fully described by us. We discovered incidentally that this method effected a saving of insulin amounting to 46.6 per cent. in seven patients. Various critics have asked why other workers have not effected a saving by using intravenous insulin. Further, we have been asked what advantages are to be gained by giving insulin intravenously apart from this saving of the drug; whether intravenous insulin adds any dangers to the treatment, and whether it brings about a remission in schizophrenia comparable with intramuscular insulin. We have had more than a year's experience with the use of intravenous insulin, and this paper aims at describing our first year of this experience and answering the questions set out above. We may mention that in 24 additional patients treated, an average saving of 28.3 per cent. of insulin has been effected.

The thyroid, as one of the glands of internal secretion to be studied first and subsequently most intensively, was early regarded with interest in relation mental disorder. Its role in the production of cretinism and in myxoedema in which the activity of the gland is diminished, as well as the association of thyrotoxicosis with psychic changes, suggested that anomalies of this organ might be linked with some forms of mental disease.

The study of prognosis in mental diseases does not easily lend itself to exact definitions, nor can its conclusions readily be based upon scientifically prepared data.

The operation of prefrontal leucotomy first performed by Moniz (1) in 1936 in Lisbon will be by now more or less familiar to most psychiatrists, on paper if not in actual practice.

At first sight the operation would appear to be a revolutionary proceeding; and so it is in some ways. It is, however, no more drastic than the convulsion or insulin treatments in which the patient is near enough the line which separates life and death.

In 1936 Tomesco (1) and his co-workers described changes in the crystallization of sodium chloride produced by the addition of small amounts of cerebrospinal fluid to 0.8 per cent. saline. A drop of *8 per cent. NaCl solution dried on a microscope slide at 75° C. produces a thin circumference of crystals surrounding an empty space. If normal C.S.F. is added in proportions of 1 C.S.F. to 20, 40 or 60 parts saline the central empty space is replaced by a thin translucent film of crystals, which in the higher dilutions begins to show lacunae. In a dilution of 1 in 120 this translucent film is reduced to a narrow strip along the inner margin of the circumference. Microscopically the translucent area is found to consist of concentric circles, feather- or spear-shaped crystals, parallel lines, needles, etc., well organized in the low dilutions, but not organized in a dilution of 1 in 120. This is regarded as the normal crystal picture.

The multiplicity of classifications of the psychopathic personality shows how important it is that a definite effort should be made to limit the syndrome, and to prevent a number of indefinite conditions being classified under this heading. The greatest danger appears to be to allow any prepsychotic state to be labelled with this diagnosis. If there is slight but definite evidence of an abnormal psychotic state, this diagnosis should be made. As pointed out the inclusion of the milder cyclothymic cases and early schizoid cases under the heading of psychopathic personalities complicates and confuses a type of psychiatric work already vague and indeterminate.

Returns have been available since the early days of the war of naval cases diagnosed as suffering from neuropsychiatric disorders admitted to the various R.N. hospitals and sick quarters in Great Britain. The following table gives an indication of the relative frequency of the different diagnostic groupings for the year 1940. These figures are in certain respects misleading. For example, uncomplicated cases of head injury would seldom be included.

Finding the blood-sugar level uncorrelated with the clinical symptoms of hypoglycaemia, Day and Niver (2) tried to establish the sugar level in the cerebro-spinal fluid as an indicator of the onset of coma. After examination of the sugar in both fluids every half hour from the injection of insulin until feeding of the patient, they found that coma began when the C.S.F. sugar reached a point between 30 and 15 mgm. per cent., whereas blood sugar was at its lowest point several hours before. The ratio C.S.F. sugar/blood sugar, normally between 10/8 and 10/6, was according to these authors “completely reversed” from the first hour after insulin injection onwards. They base their views on 43 observations of which only one was divergent, but no detailed figures are given. The four curves reproduced for illustration show the slow fall of C.S.F. sugar against the rapid falling blood-sugar level; but the alleged close correlation between coma and C.S.F. sugar can only be seen in one of the curves.

This paper is devoted to investigations into the resistance of the skin to a direct current, measured daily in normal and mental subjects. These investigations arose out of special studies in the endocrinology of mental disease, and revealed some correlation between the diurnal resistance and endocrine functioning.

The resistance of the body to the passage of a direct current is not a true resistance, being a complex phenomenon in which ohmic resistance and polarization are concerned. It has usually been referred to by other workers as the DC resistance of the skin, and has been expressed in ohms when measured with the type of apparatus used in this study. With apparatus of this sort, various workers have reported fluctuations. In this paper, although fluctuations are referred to as changes in diurnal resistance, they are in reality an effect, and not in the strict sense a resistance change. It is with the alterations in this effect in a variety of psychiatric and endocrine conditions that this paper is concerned.

The literature relating to mongolism is extensive and for the present purpose it need not be reviewed. The hand has been mentioned in almost every study on mongolism. Crookshank (1931) has given it an important place in his provocative book, The Mongol in Our Midst, without enlarging our knowledge of the now familiar features in shape and crease lines of the hand. Penrose mentions in The Creases on the Minimal Digit in Mongolism (1931) that in a certain number of cases one crease line on the fifth finger is lacking, which makes the fifth finger look almost like a second thumb. Very recently Harold Cummins of the Tulane University, U.S.A., observed a certain anomaly in the dermatoglyphs of the hands of mongoloid imbeciles (1939). He comes to the conclusion that in the finger-tips of these hands there is a noteworthy reduction in the occurrence of the whorls, and that of the five palmar patterns, hypothenar, second interdigital and third interdigital patterns are increased in frequency, while thenar/first interdigital patterns are less frequent, and also that frequencies of hypothenar types depart widely from the normal. C. E. Benda mentions that ossification of the carpal and long bones is early and that growth of the bones comes to an early end; this might account for the short hands in mongolian imbeciles (1939).

The measurements described in Dr. Hemphill's paper are nominally of resistance to a direct current, but in view of the well-known variations in resistance according to the frequency used, it seems most probable that the actual phenomena reported are due not only to changes in resistance proper, but also to fluctuations in the E.M.F. generated by the superficial tissues, as a result of the small steady polarizing current used in the Wheatstone bridge circuit.

Whereas fall of body temperature is always a danger signal in ordinary starvation and only occurs just before the end, in hypoglycaemia changes of temperature take place in an early stage parallel with the characteristic neuropsychiatric signs. Many workers (Sakel, Gellhorn, Fortuyn and others) have observed and commented on the drop of temperature in coma. The present paper is an attempt to describe the fluctuations of temperature during insulin treatment of psychoses and their correlation with the clinical signs of hypoglycaemia and to discuss their significance.

The reduction in the incidence of pulmonary tuberculosis among chronic psychotic cases has been one of the most striking indications of the improvement in conditions of institutional care during the present century. Provided that he is sufficiently co-operative, the patient who enters a mental hospital with an active lesion has generally at least as good a prospect of recovery as the patient who attends a general hospital or dispensary for a lesion of similar severity. For even if the nature of his mental disturbance may sometimes be such as to make his attitude to the illness unsatisfactory, he is often relieved of that fear of economic stress and feeling of obligation to his dependents to return to work as soon as possible, which so often prejudices recovery in the patient of sound mind.

The term narcoanalysis may be applied to a technique whereby psychotherapeutic principles are applied and analytical investigations are conducted with the patient under treatment in a mild narcotic state.

This paper reports an attempt to determine the nature of dementia by analysing the results of mental tests applied to groups of patients clinically estimated to be demented in varying degree.

Previous investigations.—The relevant literature concerns the results of mental tests in psychosis and in normal senility. These topics having been recently fully surveyed elsewhere (Brody, 1942a), they need occupy no space here.

The strong association between psychosexual anomalies and mental illness was first brought out by the work of Krafft-Ebing (1902) and Freud (1905). Freud (1911) demonstrated the existence of a latent homosexual element in the structure of the paranoid reaction. He also held the view that, to some extent, every person is psychologically bisexual. A preponderance of instincts concordant with physical attributes of sex, however, would be expected in normally developed adults. The experimental analysis of masculine and feminine traits, carried out by Terman and Miles (1936) with an attitude—interest test, led to conclusions which were in accordance with this viewpoint. Terman and Miles were also able to show that frankly homosexual males and females had mental preferences which corresponded with those of the simulated sex. Thus, from the psychological standpoint, sex is a graded character with a bimodal overlapping distribution. That is to say, although most males and most females have mental attributes which are in agreement with their sexes, many also are mentally intermediate and lie between the two normal modes. Furthermore, some are excessively masculine, some excessively feminine, and a few, who can be said to be “inverted,” possess mental attributes, which belong normally to the other sex. No mental disability has so far been shown to be associated with excessive mental masculinity or femininity, though Terman and Miles found that “supermales” were, on the whole, poorly developed physically. On the other hand, a marked degree of sex inversion is known to be unfavourable to mental stability. Indeed, a significant trend towards sex inversion as measured by the Terman and Miles test has recently been demonstrated by Bosselman and Skorodin (1940) in psychotic patients. A somewhat similar result was obtained by Neal and Penrose (1941), who used a classification test.

Following the work of Dale (1934) and Loewi (1935) on the relationship of choline esterase to the transmission of nervous impulses, a number of studies have been made of the choline esterase activity of the serum in different physiological and pathological conditions. The serum esterase activity varies considerably from one individual to another, but it generally remains very constant in any one individual even over long periods of time; it is believed to be unaffected by changes in diet, exercise, fatigue, or by menstruation. The earlier investigators were unable to correlate the esterase level with any such factor as age, sex, heart rate, blood pressure, weight, or with pathological conditions such as benign or malignant tumours, chronic infections, heart diseases or neurological conditions (v. Verebely, 1936; McGeorge, 1937); they found only a tendency to low esterase activities in acute infections (Hall and Lucas, 1937) and in advanced tuberculosi (Vahlquist, 1935).

In an investigation in which psychopathic patients were included Tod and Jones (1937) and Jones and Stadie (1939) described a number of positive correlations between the serum choline esterase and various clinical conditions. They found a high esterase activity in anxiety states and lowered activity in catatonic stupor, epilepsy, schizophrenia and also in advanced tuberculosis and carcinoma. Antopol et al. (1937, 1938) associated high serum esterase activity with thyrotoxicosis and low activities with liver disease, anaemia and hyperpyrexia. Milhorat (1938), in agreement with Jones and Stadie, attributes the low esterase activities in these conditions to the general debility, but McArdle (1940) concludes that impairment of liver function is the primary cause.

The present work was carried out with the object of obtaining further information as to the relationship between the serum choline esterase activity and anxiety.

The value of electro-encephalography as an aid to the study and diagnosis of nervous diseases is now accepted. The most valuable results have been obtained in cases of organic disease of the brain, particularly in space-occupying lesions and in epilepsy, but considerable attention has also been paid to the changes occurring in cases suffering only from mental disorder. The chief contributors to this subject are listed in the bibliography.