The psychiatric aspects of multiple sclerosis (MS) have been given considerable attention in the literature over the past 130 years. There has, however, been little unanimity of opinion as to the incidence, severity and nature of the changes seen in the mental state of sufferers from this disease. Early investigators regarded intellectual deficits as the main disturbance, and noted that emotional lability was not infrequently present.

Homicide is a universal phenomenon which occurs both among developed and developing communities, but to a varying extent. Homicide in this context does not include the lawful killing of criminals convicted of capital offence, or killing in war or in conditions of political strife. Considerable work has been done on various aspects of criminal homicide in many countries—Verkko (1951) in Finland, Jacqueline H. and Murray A. Strauss (1953) in Ceylon, Wolfgang (1958) in the United States. The book African Homicide and Suicide edited by Paul Bohanan (1960) contains only a chapter on homicide among the Tivs of Central Nigeria, and this is based on a retrospective study of case files. Lambo (1962) reported twenty-nine cases which he had interviewed for the courts; these came from the whole of Nigeria, and therefore represent different peoples and cultures.

Stereotactic surgery has provided a means of producing accurate lesions at selected points in the nervous system where concentrations of nerve cells or fibre pathways possessing specific functions permit some small area of anatomical destruction to produce widespread physiological effects. The value of this method in relation to motor and sensory activity is illustrated by the results of thalamotomy in the treatment of Parkinsonian tremor and by stereotactic division of the spinothalamic tract in the cervical cord for the relief of incurable pain. The accuracy of approach and minimal disturbance of tissue ensures that the beneficial effects of these operations are produced in isolation without associated disfunction in the nervous system. That a similar principle can be applied in relation to the control of emotion has been shown in cases of intractable psychoneurosis treated by the operation of bifrontal stereotactic tractotomy in the substantia innominata (Knight, 1964). Owing to the influence of emotion in psychoneurotic states it is possible to influence many syndromes satisfactorily by operation at a site where connections of the limbic system concerned with instinctive and emotional activity rather than cognitive processes converge to a point beneath the head of the caudate nucleus, thereby producing a reduction in the intensity of emotional reaction without undesirable personality change or post-operative epilepsy. It is felt that it would be useful to summarize the anatomical features in order that the differences between this operation and the old leucotomy procedure can be generally appreciated. It is particularly among cases of chronic and recurrent depression that this form of surgery can be most usefully employed.

Surprisingly little is known about the course of intellectual development in children with infantile psychosis. Kanner (1943; Kanner and Lesser, 1958) has stated explicitly in several papers that “even though most of these children are initially considered feeble-minded, they are all unquestionably endowed with good cognitive potentialities, which are masked by the basic disorder” (original italics—Kanner and Lesser, 1958). The expectation would seem to be that the child's IQ, should fluctuate with the course of the psychosis, particularly the autistic aspects, but this has not been tested. It has been suggested (Anthony, 1958) that an intelligence test result in a young child with infantile psychosis is most unreliable and virtually meaningless if the child is without speech. Perhaps because most investigators have shared this view, neither of the two major follow-up studies of children with infantile psychosis, that of Kanner's cases (Eisenberg, 1956; Eisenberg and Kanner, 1956; Kanner, 1943 and 1949; Kanner and Eisenberg, 1955; Kanner and Lesser, 1958) and that of psychotic children seen by Creak (1962, 1963a and b) has included information on IQ changes.

In recent years several factor analytic studies of the depressive states have referred to the problem of the so-called endogenous and neurotic varieties of depression. Some authors (Hamilton and White, 1959; Kiloh and Garside, 1963; Carney et ai, 1965) have found a bipolar factor corresponding to the supposed endogenous—neurotic dichotomy or to an anxious retarded dichotomy (Hamilton, 1967) while others have not (McConaghy et al., 1966). Rosenthal and Gudeman (1967a, b) found two orthogonal factors which they felt described an endogenous (or autonomous) depressive syndrome and a self-pitying syndrome. Differences in selection of patients or in interpretation of results, and unconscious bias in recording clinical data (Oswald, 1966) have been held to be responsible for these discrepancies.

I am particularly grateful for the privilege of delivering the first Mapother Lecture. I believe it will be appropriate to devote it to a review of Professor Mapother's life and his work in shaping the Maudsley Hospital, with which he is inseparably connected. It is nearly thirty years since his death. The course of events since then has shown on what sure foundations he built. Those like myself who had daily contact with him during the later years of his life felt great respect and admiration, as well as warm affection, for him; but it is only in the perspective of recent history that the full measure of his achievement can be seen: perhaps not even yet. In preparing this Address I have been mindful of what Sir James Crichton-Browne said when delivering the first Maudsley Lecture in 1920—‘the last thing the donor of this Lectureship, retiring and shy of publicity as he was, would have wished would be that its inaugural discourse should be devoted to any elaborate eulogy of himself.’ It is an éloge rather than a Eulogy that I would wish to put before you this evening; Condorcet, a master of the art of obituary appraisal, said that an academic éloge should not be a panegyric but an effort to report the truth about a scholar and to do him full justice.

‘As for the bodily temper of man and his Brain… a very little distemper of the brain… is enough to represent Spirits, Angels and Devils, Sights and Stories of Heaven and Hell to the Fancy… which sober kind of madnesses and delineation (is) little understood vulgarly’.

“… they both felt, after the conclusion of their work, very doubtful as to the possibility of definitely proving the existence of a real differential incidence of any character in order of birth. The whole question seemed so open to fallacious possibility in different directions.”

[Report of comment by G. Udney Yule in the discussion following his joint paper with M. Greenwood at the Royal Statistical Society in 1914.]

Recently there has been an upsurge of interest in the association between behaviour, both normal and abnormal, and birth order. For instance, Barry (1967) has pointed out that in certain societies excessive parental demands are made on the first-born child, and “excessive parental demands could lead to superior achievement in a robust individual or to psychiatric illness in a child who was especially vulnerable …”; thus putting into modern language an interesting genotype-environment interaction which was summed up in the ancient Chinese proverb “fire burns wood but tempers iron”.

Tics or habit spasms have been described in various ways, but perhaps the most useful definition is that of Kanner (1937) that they are “quick, sudden and frequently repeated movements of circumscribed groups of muscles, serving no apparent purpose”. Children with this symptom not infrequently present to the paediatrician or child psychiatrist with accompanying symptoms of emotional disturbance, and by the age of seven years approximately five per cent of children have a history of such movements (Kellmer Pringle et al., 1967). Less commonly, adolescents who have suffered with tics from an earlier age develop vocal tics and coprolalia (compulsive swearing) symptomatic of Gilles de la Tourette's syndrome. Tiqueurs are rarely seen for treatment in adult life, except in a few well-documented cases where Gilles de la Tourette's syndrome persists (Fernando 1967).

Previous studies on schizophrenia in twins have quite recently been reviewed in detail by Gottesman and Shields (1966a) and Shields (1968). The indications of concordance in different series are highly diverging, in monozygotic pairs ranging from near unity to zero. The high concordance rates found by Luxenburger (1928), Kallmann (1946) and Slater (1953) stress the importance of genetic factors in the aetiology of schizophrenia, whereas the low concordance rate in two recent Scandinavian twin series (Tienari, 1963; Kringlen, 1966) has given rise to the question whether special genetic or environmental factors prevail in some populations. It has, therefore, been found of interest to study schizophrenia in a Danish twin population.

The rules known as Koch's postulates have served as invaluable guides to the discovery of the specific causes of various infectious diseases. It may safely be assumed that their influence has also been great on the methods of study in the field of non-infectious diseases. For example, with slight modification Koch's postulates may be applied to the study of diseases caused by poisons. But can they be modified and applied with profit in psychiatric research? This is an important problem, and it cannot be discussed without reference, explicit or implicit, to philosophical assumptions. In this paper some consequences of the philosophy of science of Sir Karl Popper will be tentatively explored.

There are only four studies which deal exclusively with the electroencephalographic investigation of murderers (Stafford-Clark and Taylor, 1949; Hill and Pond, 1952; Mundy-Castle, 1955; Winkler and Kove, 1962). In several other reports, murderers are included as a sub-group of a population described as psychopaths and criminal offenders (e.g. Silverman, 1943, 1944). The general finding of these studies was that the murderer population had an incidence of EEG abnormality far above that found in non-criminal, non-psychiatrically ill subjects. However, the range of incidence of abnormality was large, being from around 20 per cent to 80 per cent. Despite the complex psychopathology commonly leading to an act of murder, it has been not uncommon to conclude, from the finding that the populations studied had a high incidence of epilepsy, that there was some association between epilepsy and murder. Alström (1950), however, in a study of 897 epileptics, found that no patient had committed a crime during psychomotor seizure. The Jack Ruby Trial in America highlighted the assumed association and Livingston (1964) summarized the true situation: ‘… an epileptic might kill, not because he has epilepsy, but because he is a human being …’.

The purpose of this paper is to present some of the findings concerning the morbidity rate of monozygotic co-twins of schizophrenics and the possible influence on it of environmental factors. The work is based on a statistical study of the clinical records available at the MRC Psychiatric Genetics Research Unit.

In a previous paper (Kay et al., 1969) the mode of selection and composition of a sample of 104 depressed patients was described. The present article concerns the follow up of this sample, 5–7 years after the index admission (which was always a first admission). The aims were: (i) To examine and compare outcome in three groups of patients, “endogenous”, “neurotic”, and “undifferentiated”, (ii) The second aim was to study the power of various individual features to predict the course and outcome of the illness. The patients' groups were defined by the factor scores on a first (bipolar) factor which was identifiable in many though not all respects with the “endogenous-neurotic” factor previously described by Kiloh and Garside (1963) and by Carney, Roth and Garside (1965). A full account of the symptoms defining the factor, which was obtained by principal components analysis, and of the method of allocating patients to the diagnostic groupings, was given in the previous paper.

Reserpine, which depletes brain amines, not infrequently causes depression (Bunney and Davis, 1965), whereas monoamine oxidase inhibitors (MAOI) which raise brain amine levels (Maclean et al., 1965) may alleviate depressive symptoms. The alleviation has been reported to be enhanced by tryptophan (Coppen et al., 1967), which is a precursor of the amines 5-hydroxytryptamine (5HT) and tryptamine. The apparent prophylaxis by tryptophan of an annual episode of depression has also been reported (Hertz and Sulman, 1968). These findings suggest that elevation of one or both of the above amines is responsible for the therapeutic effect of MAOI, and that their insufficiency may be responsible for symptoms of the disease. Defective 5HT synthesis in depressive illness is indicated by a number of findings. (1) Depressed patients responding to the MAOI drug iproniazid were found in two studies (Pare and Sandier, 1959; Praag and Leijnse, 1963), though not in a third (Burgermeister et al., 1963), to have a lower initial urinary excretion of the 5HT metabolite 5-hydroxyindole acetic acid (5HIAA) than those who did not respond. (2) Depressed patients have a low content of 5HIAA in the lumbar cerebrospinal fluid (Ashcroft et al., 1966), which rises on recovery. Although work using animals (Guldberg and Yates, 1968; Eccleston et al., 1968) shows that changes in brain 5HT are paralleled by changes of 5HIAA in the CSF, the significance of this result is not altogether clear, as lumbar 5HIAA depends not only on brain 5HT metabolism but also on 5HIAA transport within the CSF (Ashcroft et al., 1966). Furthermore, a small group of acute schizophrenics on phenothiazines also had low 5HIAA. (3) There is some direct evidence of low 5HT (Shaw et al., 1967) or 5HIAA (Bourne et al., 1968) in the hindbrains of depressive suicides. (4) While single doses of 5-hydroxytryptophan, the immediate precursor of 5HT, do not alleviate depression, the remission of a prolonged episode of severe depression by administration of 5-hydroxytryptophan for five days has been reported (Persson and Roos, 1967).

In a previous paper (Price and Hare, 1969) we drew attention to some types of bias which may complicate the search for a useful association between disease and birth order. In particular, we considered biases occurring in a sample of adult patients where the patients' mothers have all passed their reproductive period and where, therefore, the sibships of the patients are complete. In such a sample, the recognized methods of searching for an association between disease and birth order are based on the assumption, that, for a null hypothesis, the sample will be randomly distributed among the birth ranks for each sibship size. But in fact the distribution may be non-random, and there are two main causes for this. These are (i) changes in the birth rate of the population, and (ii) changes in the birth rank distribution of the patients between birth and the age-range from which the sample is selected (e.g. differential rates of mortality or migration). The principal aim in the present paper is to illustrate the bias arising from the first of these causes.

If a person is faced with some potentially frightening task such as making a speech, then the company of a friend, who contributes nothing directly, may improve the delivery of the speech by his emotional support, more traditionally called moral support. It seems the same article as that which ought to be supplied to a child by its parents, to a patient by his therapist, or to a worker by his supervisor so that efficiency can develop and be maintained. However, a therapist or a supervisor may not know when emotional support is being given; sometimes the presence of another person can be embarrassing, and so a normally efficient pattern of behaviour may be disturbed. For this reason an examination of the nature of support seems warranted.

The possibility of a relationship between early parental loss and mental illness, suicide, or delinquency in later life is a well-known, although by no means universally accepted, theory. In this investigation, we have attempted to compare patients with carefully matched controls and to investigate, when possible, the various categories of depression separately. Also, as we felt that a study concerned with childhood deprivation based solely on the physical absence of parents would tell us little of the daily emotional experiences of the child, we have attempted to take into account the quality of the family relationships present in childhood.

In previous studies the estimation of the incidence of intellectual changes in multiple sclerosis has varied from as low as 2 per cent. (Cottrell and Wilson, 1926) to as high as 72 per cent. (Ombredane, 1929). In order to establish the incidence accurately, the most satisfactory method would clearly be a long-term follow-up (covering lifetime) of a sample of multiple sclerosis patients. Any cross-sectional study would include patients in varying degrees of advancement of the disease, and patients found to be free of intellectual deficits at the time of investigation would not necessarily remain so. Also, the indirect psychometric assessment of intellectual loss is notoriously difficult, and the direct method of follow-up would give much more accurate results. The only direct study up to date has been that of Canter (1951), who found a highly significant (i.e. 13·48 points) loss on re-testing multiple sclerosis patients on the Army General Classification Test after a four-year period. Even after such a short period as six months he found slight losses on most Wechsler-Bellevue subtests, in contrast to an average gain of six full IQ points of the control group.