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.

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).

Recent investigations suggest that there may be an abnormality of calcium and magnesium in depressive illness. Flach (1964) followed the urinary excretion of calcium in depressed patients maintained on a constant intake of calcium before and during recovery. Those patients that recovered showed a significant decrease in the excretion of calcium. Coirault et al. (1959) reported an increase in ionized calcium and a decrease in total plasma calcium on recovery from depression. Cade (1964) reported considerably raised total plasma magnesium levels in depressed patients both before and after recovery. A connection between affective disorders and calcium metabolism is suggested by the common occurrence of such states in both hypo- and hypercalcaemia (Denco and Kaelbling, 1962; Rookus and Speelman, 1961). The present paper reports an investigation into total and ionized plasma calcium and magnesium in a group of depressed patients both before and after recovery. The effects of lithium carbonate, a compound used in the treatment and prophylaxis of affective disorders (Baastrup and Schou, 1967; Schou, 1963) on plasma concentrations of magnesium and calcium was also investigated.

In studies which attempt to assess the efficacy of some new treatment it is customary to make a formal assessment of the relevant behaviour or symptomatology using standardized inventories, checklists, symptom rating scales or ad hoc ratings of variables considered to be important by the clinician-researcher. Ratings made at the beginning and end of treatment are compared for groups of patients using improvement scores, arbitrary cut-off points and other devices aimed at circumventing the statistical problems arising from the non-normal distributions of most rating scales. Present practice favours the use of some nonparametric statistic in these comparisons. The aim of this paper is to present a method which facilitates the analysis of ratings made on more than two occasions, allowing a trend analysis to be carried out without making assumptions about the distribution of scores. The method also allows the clinician-researcher to make a statistically-based decision regarding the efficacy of the treatment in question for individual patients.

It has been suggested by Philip (1969) that more information could be gleaned from conventional drug trials if it were possible to assess the efficacy of treatment for each patient in the trial. A method for the statistical analysis of individual response to treatment has been put forward by Philip using a modification of Ferguson's nonparametric trend analysis of correlated observations (Ferguson, 1965). Sutherland, Sutherland and Philip (1967) have described the details of a double-blind drug trial in which the efficacy of Prondol, an imipramine derivative, was compared with a standard imipramine preparation. The patients in their trial were rated on the Hamilton scale for depression (Hamilton, 1960) on admission, after two weeks' treatment and after four weeks' treatment. Since the data were not amenable to analysis by parametic methods, Mann-Whitney U tests (Siegel, 1956) were calculated to ascertain whether the change scores between rating occasions were different for the two groups of patients. This cumbersome procedure showed that there was no difference in change scores between the trial drug group and their controls for the 0–2 week and 0–4 week comparisons; there was, however, a significant tendency for the control drug group to show significantly greater change between the two week and four week assessments.

“Much doubt persists about the different benefits from, and indications for, all the many drugs proposed for the relief of anxiety” (Lancet, 1965). Chlordiazepoxide is one of the most popular minor tranquillizers used by psychiatrists, physicians and general practitioners. Its efficacy has been advocated in the “Today's Drugs” column of the British Medical Journal (1967, 1968a and b). Others, however, have been “impressed by the number of patients who claim great benefit but show little evidence of this” (Jenner, 1965).

Nitrazepam is a benzodiazepine closely related to diazepam and chlordiazepoxide. It has been marketed as a sleep-inducing drug, and as such has proved to have an overall effectiveness comparable to that of the barbiturates and related drugs (3, 4, 5, 6, 8, 12).

All hitherto applied antidepressant drugs, both the tricyclic compounds and the MAO inhibitors, present serious disadvantages, not only some more or less grave undesirable side-effects, but also a rather long latency time before the antidepressant effect itself strikes through.

The tricyclic antidepressant drugs are established therapeutic agents, yet their mode of action has remained obscure. The usual delay of some 10 or more days before they produce beneficial effects has never been satisfactorily explained. Many months are usually necessary for lasting cure, for often symptoms recur when the drugs are stopped. If they are then reinstated for several months, and then stopped, the patient commonly remains free of symptoms. There is thus uncertainty as to whether the drugs might simply be masking the depression in a manner comparable to anxiety-relieving agents, and uncertainty whether patients should be regarded as temporarily dependent upon tricyclic drugs. Slow brain processes have to be inferred, of a duration often met in psychiatry (Oswald, 1967). The observations we now report have features in common with many other slow brain recovery processes Oswald, 1969) and may cast light upon the mode of action of antidepressant drugs, as well as providing further insight into the chemical mechanisms of sleep. The latter are currently believed to be governed in part by cerebral mono-amines, which the tricyclic drugs are thought to affect.

Propranolol is a β-adrenergic blocking drug and so relieves symptoms due to excessive adrenaline release, and in particular slows the pulse rate, even in normal subjects (Bollinger et al., 1965). Because of this, Granville-Grossman and Turner (1966) undertook a double-blind trial of propranolol against placebo, showing that it was effective in anxiety. The General Practitioner Research Group has used chlordiazepoxide in comparative trials to new drugs in the treatment of anxiety (G.P. Clinical Trials 1968), under grants from the National Institute of Mental Health, U.S. Public Health Service (MY–4135 (CI), MH 0413–05 and PH 43–65–626). It was therefore decided to compare propranolol in like manner to chlordiazepoxide, in cases of anxiety neurosis seen in general practice.

In his Upjohn lecture Professor G. W. Harris (1964) reviewed experiments on the effects of gonadal hormones on the sexual behaviour of animals. He compared sexual behaviour patterns of male rats castrated on the first day of life with those of adult castrates. When fully grown, these day-old castrates were either primed with oestrogen and progesterone and tested for female mating behaviour, or they were given testosterone and tested for male behaviour with receptive females. Thus, Harris was able to demonstrate bisexual behaviour (mediated through hypothalamic-pituitary pathways) with female type activity cycles occurring in male rats. These experiments suggest that gonadal hormones exert a dual effect. During the early phase of development they act inductively, and later in the adult they exert an excitatory action on the central nervous system.

Until recently it was a widely held opinion that little could be done to alter the sexual orientation of homosexuals (Curran and Parr, 1957). Most therapists confined their efforts to helping the homosexual to adjust to his role. Now opinions are beginning to change. Bieber et al. (1962) with psychoanalysis and MacCulloch and Feldman (1967) with aversion therapy have reported a significant number of successes—where homosexual orientation has been lost and heterosexual orientation gained.

This paper is an attempt to fill the void in objective investigation into the personality factors of lesbians. Although the subject of male homosexuality has been investigated exhaustively, it was not until relatively recently that studies concerned with lesbianism have been published, beginning with Armon (1960), then Bene (1965), Kaye et al. (1967) and Kenyon's series of articles in 1968. These papers have all attempted to take the subject out of the myth and psychoanalytic theory stages and bring it into the light, to determine whether the many theories, which at times have been based upon knowledge gleaned from male homosexual studies, have any objective, quantifiable basis. For example, one view stated by Caprio (1957) ‘that the vast majority of lesbians are emotionally unstable and neurotic …’ is a view commonly held as true almost by definition in psychiatric circles. It might be that this type of observation has been too subjectively made, on the basis of psychiatric interviews of otherwise neurotic women, who also may have been homosexually inclined.

Diagnosis of adolescent psychiatric patients is complicated by the absence of history of function in an adult role and by the assumed presence of psychological turmoil, thought to be normal at this age. Information about prognosis, always a useful part of clinical management, is especially important in counselling adolescent patients and their families about the prospects for education, vocation, and marriage.

†Patients came from both rural and urban areas of several neighbouring states. Parents or guardians of approximately one-third were teachers, salesmen, or shopkeepers and of another third, skilled labourers or farmers. The remainder were approximately equally divided between the well-to-do at one extreme and unskilled labourers at the other. That this sample provided a wider distribution among social strata than most private hospitals or most public hospitals is borne out by the fact that some patients who were subsequently hospitalized again were treated in private hospitals while others were admitted to public facilities (state hospitals).

1. The Royal Medico-Psychological Association, being the largest body of medical professional workers most likely to be affected by the establishment of a Hospital Advisory Service, at least until this is developed to cover the whole of the Hospital Service, and being a constituent member of the Joint Consultants Committee, welcomes the Secretary of State's recent statement of intention to establish an Advisory Service which will contain a system of hospital inspection.