Too deeply moved to search for originality of expression, I hope that you will allow me to fall back on some of the well-worn phrases in acknowledging the honour conferred on me when I was chosen to be this year's Maudsley lecturer. My reaction was summarized in my reply to the notice which reached me in May, 1957. I wrote: “I accept amidst an understandable struggle between pride and humility. The name ‘Maudsley Lecture’ has an almost hallowed connotation among my professional contemporaries, and this invitation comes to me as a sort of crowning acme of my career.” I am delighted to share my laurels with the Johns Hopkins University, which I joined exactly thirty years ago at the call of Adolf Meyer, whose gigantic contributions to psychiatric theory and practice were attested by the Royal Medico-Psychological Association when he was nominated to be the fourteenth Maudsley Lecturer in 1933. In going over the list of my illustrious predecessors in this series of addresses, beginning with Sir James Crichton Browne and Sir Frederick Mott, I find that I am the second United States psychiatrist to receive so great a distinction. I am certain that I voice the sentiments of my University when I say that it considers this event as an added and happily displayed feather in its richly decorated cap. The Johns Hopkins University has recognized the growing importance of child psychiatry by creating a full professorship in this discipline, and I am pleased to be the symbol of this recognition. And now your Association has indicated its desire that I speak as a child psychiatrist “as this specialty has not been covered in a Maudsley Lecture before”. To have been selected as the first spokesman for child psychiatry in this group is a thrilling experience laden with heavy responsibilities.

Dementia paralytica is a declining disease. Deaths due to it in England and Wales were first recorded by the Registrar General in 1901 and since that year, when the number was 2,272, the annual figure has fallen steadily until in 1957 it was only 68. Moreover, there is evidence (adduced below) that not more than a small part of this decline can be attributed to improvements in medical treatment. The fear that there might be a recrudescence of dementia paralytica as a result of the spread of syphilis during the second world war has not so far been realized and it seems likely that what is now, in Great Britain at all events, an obsolescent disease will soon become a rarity. Yet there are many unsolved problems in its history. We do not know, for example, why the alleged references to this striking disease were so few and so inadequate until the third decade of the nineteenth century. We do not know why its recognition in many countries was so tardy in spite of the clear description given by the French alienists. Nor do we know why the disease, which at the start of the nineteenth century seems to have been predominantly one of males, has gradually—and at different rates in different countries—become much more evenly distributed between the sexes.

For many years, schizophrenic thought disorder has been regarded as being due to an abnormality of concept formation of some sort. However, there has not been general agreement about the nature of this abnormality. Kurt Goldstein and his followers (9, 32, 33) have argued that schizophrenics are abnormally “concrete”. That is to say, they are unable to perform inductive reasoning, since they are unable to make an abstract generalization. Norman Cameron (11, 12, 13, 14, 15, 16, 17, 18, 19) on the other hand argues that in one sense at least, schizophrenic concepts are over-generalized. He believes that the concepts formed by schizophrenics are “over-inclusive”. They are unable to maintain the normal conceptual boundaries, and incorporate into their concept elements (some of them personal) which are merely associated with the concept, but are not an essential part of it. This makes their thinking both over-general, and less precise than normal. A large number of studies have been carried out to test both these hypotheses.

In the April, 1952 issue of this journal, Osmond and Smythies (47) suggested that schizophrenia might be caused by a defect in adrenaline metabolism. They called this hypothetical adrenaline derivative “M-substance” because they endowed it with mescaline-like psychotomimetic qualities but with an effective potency nearer that of adrenaline or even the hugely powerful LSD-25. They showed that mescaline and adrenaline were sufficiently alike chemically for such an intermediate to be at least imaginable. In addition, they emphasized that the mescaline experience and the more acute and dramatic forms of schizophrenia have many similarities. They hoped that researchers would hunt diligently for our M-substance.

Investigation of the urinary excretion of indoles in psychotic illnesses has a certain historical precedent. Thus Townsend (1905) and Bruce (1906) reported excess of indican in the urine of melancholic patients. Bruce correlated this finding with the recognized tendency to constipation in depressives and treated his patients with enemata. Ross (1913) reported that schizophrenic subjects excreted an excess of indole-acetic acid in the urine. De Jong (1945) reported the experimental induction of catalepsy in cats by the intravenous administration of indolethylamine and noted in his monograph that this substance, if perfused in vitro through the liver, is converted to indole-acetic acid. Buscaino (1952) reported finding abnormal amounts of primary and secondary amines in the urine of schizophrenics. More recently Riegelhaupt (1956, 1958) has reported an excess of tryptophan metabolites in schizophrenic urine while McGeer and co-workers (1957) have reported a difference in the excretion of aromatic substances as between normals and schizophrenics. Though these authors do not make the point clear, yet in fact indoles come under the general heading of aromatic substances.

In Part I of this communication the theoretical basis for the investigation was outlined. Details of a statistical study were given and it was suggested that these confirmed a greater incidence amongst schizophrenics than normals of subjects excreting an excess of indole substances. In addition the question of hepatic dysfunction was investigated in 48 schizophrenic patients using the Cephalin-Cholesterol Flocculation Test. The results of this investigation were essentially negative.

Since its introduction in 1938 electroshock therapy (E.C.T.) has become probably the most widely applied form of physical treatment in psychiatry, despite the fact that its method and site of action are still not precisely known. Numerous investigations have been undertaken to delineate more clearly the indications for its use; notwithstanding broad agreement as to its value in depressive states and some schizophrenic syndromes there is still a paucity of evidence on which firm criteria for the prediction of outcome to treatment can be based. Most prognostic studies appeared in the first decade following the introduction of E.C.T. and were based largely on empirical clinical observations during the course of routine psychiatric practice, whereas later investigations have included more intensive and precise researches into possible psychological, physiological, biochemical and pharmacological indices of capacity to respond to electroshock.

During the past ten years varying degrees of prognostic value have been claimed, directly or indirectly, for a number of specific factors in connection with the treatment of depressive illnesses by E.C.T. These have included the blood pressure responses to adrenaline and methacholine (Funkenstein et al., 1948, 1950); the “sedation threshold” to intravenous sodium amylobarbitone (Shagass, 1954; Shagass and Jones, 1958); EEG changes under thiopentone following electroshock (Roth, 1951; Roth et al., 1957); and psychological tests based on items derived from the Minnesota Multiphasic Personality Inventory (Pearson, 1950; Feldman, 1957, 1958; Welsh, 1952). Other studies have been made on the prognostic value of adrenocortical activity (Faure et al., 1957); serum calcium levels (Gour and Chaudhry, 1957); the “amytal test” (Kahn et al., 1956); and the administration of methylamphetamine (“methedrine”) (Rudolf, 1956). Some of the techniques employed appear too complicated or unreliable in their interpretation to be of any practical clinical value, although a few are of great theoretical value in the contributions to further knowledge of the rationale of E.C.T.

Head injury, whether single as in an accident, or recurrent as in boxing, may on rare occasions be followed by a form of insidious dementia (Bowman and Blau, 1940). The post-mortem study of such long-standing cases however is seldom undertaken, and although various pathological processes may have been postulated during life they have rarely been looked for after death. The findings in the following case are therefore reported in some detail.

Smallness of the cranium is one of the commonest findings in severe mental defect. Ashby and Stuart (1933 and 1934) found a correlation between brain weight and mental age of +0.15, but they regarded this as part of the more general positive correlation of +0.24 which they observed between body weight and mental age. In discussing this subject elsewhere (Hilliard and Kirman, 1957), Crome and Kirman have taken a more definite stand on this matter in so far as idiocy and imbecility are concerned and regard reduced brain weight, which is so often associated with a small cranium, as one of the major factors in reduced intelligence. Crome (1957) found marked reduction in size to be the commonest abnormality in brains of low-grade defectives.

Almost 125 years ago Addison (1836) suggested the existence of a causal relationship between alcoholism and cirrhosis of the liver and more than 100 years ago Rokitansky noted accumulation of fat as the earliest effect on the liver of over-indulgence in alcohol (cited from Connor, 1938). Though the relative importance of infective hepatitis and alcoholism as aetiological agents in liver cirrhosis may vary a great deal in different countries, “alcohol and infective hepatitis are at present the only two unequivocal aetiological factors” (Annotation, Brit. Med. J., 1957). It is usually accepted that over-indulgence in alcoholic drinks often produces liver dysfunction—maybe in an indirect manner—which though reversible at first, tends to become irreversible as over-indulgence is continued and prolonged (Leevy, Cunniff, Walton and Healey, 1954). The terminal phases are characterized by cirrhosis, hypertrophic at first and then contracted, with ascites and eventual death. When individuals whose drinking habits lead them to this state need hospital treatment, they seem to find their way into general hospitals rather than into mental hospitals. Among them may be alcoholics of the type described by a World Health Organization Expert Committee as “habitual symptomatic excessive drinkers” (W.H.O. Rep., 1952) or “non-addictive alcoholics”, and those excessive drinkers whose alcoholism manifests itself in their “inability to stop” continual daily drinking in the face of dangerous consequences (W.H.O. Rep., 1955).

It is well known that a factor analysis may be carried out in various ways; the subjective elements involved make it by no means clear that two people beginning with the same data will arrive at the same conclusions. Furthermore, not enough attention has been paid to the confirmation of factors revealed in one analysis by repetition of the tests on another sample from a similar or different population.

In view of the significant role the sexual instinct plays in psychiatric illness, it is surprising that there are in the literature so few reports of attempts to suppress male sexual behaviour by the direct method of modifying the physiological basis of sexual activity by oestrogen therapy. Dunn (2, 3) established that administration of stilboestrol could result in marked reduction of male libido and sexual behaviour. He treated two non-psychotic hypersexual patients and, apart from the clinical effects, observed gynaecomastia, histological evidence of reversible testicular degeneration, and depressed urinary androgen excretion. Hamburger (6) later demonstrated in one case that oestradiol administration produced the same degree of urinary androgen excretion as did actual surgical castration of the same patient. Thus, present evidence indicates that oestrogen therapy produces in the male what is, in effect, a reversible chemical castration.

The present investigation represents a logical continuation of a previous experiment where it was shown that the injection of 5-hydroxytryptophan (5HTP) alleviates the psychological effects of lysergic acid diethylamide (LSD-25) (Brengelmann, Pare and Sandler, 1958). LSD is of interest in psychiatry because the psychotomimetic effects of the drug bear a resemblance to schizophrenia clinically, in psychological tests and, according to Hoagland, Rinkel and Hyde (1955), in their abnormal excretion of urinary phosphate. The possibility presents itself that, in some cases of schizophrenia, the functional abnormality is similar to that produced by LSD.

The following is a short report on the results obtained from 204 two-way paper chromatograms for urinary indoles. The material examined came from 58 schizophrenics, 34 organic psychoses, 58 affective psychoses (33 complicated by physical disease, and 25 not), 48 neurotics etc. (18 complicated by physical disease and 30 not) and 6 mentally normals.

In previous investigations (Foulds and Caine, 1958 and 1959) psychoneurotic subjects were classified in terms of the presenting syndrome (Hysteria or Dysthymia) and of the personality type (hysteroid or obsessive) as rated by psychiatrists. It was found that some psychological test measurements differentiated between Hysterics and Dysthymics regardless of personality type; whilst other measures differentiated between hysteroid and obsessive personalities regardless of diagnosis. The successful measures were not, however, identical for men and women. It was argued that one of the advantages of this double classificatory system should be that we would have one set of measures—the diagnostic—which should vary with the patient's clinical condition and another set—the personality measures—which should remain relatively constant.

In 1954 Shaw et al. described the action of Megimide (bemegride) in shortening sleep and restoring consciousness in laboratory animals under the influence of barbiturates. Subsequently, in 1955 Shulman et al. reported the results of the use of this drug in the treatment of barbiturate overdosage in man. Since then Megimide has been widely accepted as a valuable antidote in barbiturate poisoning, but there has been much discussion on whether it is a specific antagonist to barbiturates or a non-specific central analeptic.

Turle (1) in a double-blind trial using hydroxyzine found that of 18 patients admitted to a neurosis unit (7 anxiety neurosis, 1 obsessive-compulsive state, 6 depressive states and 1 involutional melancholia) only 3 patients showed signs of improvement on a dosage of 30 mg. by mouth, t.d.s. Only 1 out of 8 selected on account of tension symptoms was relieved. The other 2 improved cases were depressive cases with secondary anxiety features. He concluded that the drug was of no manifest benefit in neurotics. The serene tension-free effect reputedly produced by the drug and described by American workers was not observed.

A case closely comparable with that reported below does not appear to have been described, possibly because of the ethical problems involved. Watkins (1947, 1951), in the description of two cases, has made the most nearly related contribution to the old debate as to whether an unwilling subject can be hypnotized. His cases were both trained subjects who were offered money rewards to attempt to resist the formal induction of hypnosis before an audience. They were both successfully hypnotized. The fear-inspired unwillingness of the patient to be described would appear to have been in a rather different category.

Prochlorperazine (Compazine, Stemetil) and chlorpromazine (Thorazine, Largactil) frequently produce tremor and rigidity. Less well known are the severe tonic spasms of the muscles of the head and neck which can result from these phenothiazine derivatives. This paper directs attention to these spasms and their similarity with “extrapyramidal seizures” and oculogyric crises.