A meta-analysis was carried out on 53 cases of dementia praecox (DP) and 134 cases of manic-depressive insanity (MDI) originally diagnosed by Kraepelin or his collaborators in Munich in 1908. The original case material was coded in terms of Present State Examination syndromes and analysed statistically for internal consistency and discrimination between the two diagnostic entities. Kraepelin's DP and MDI were found to define homogeneous groups of disorders which could be clearly distinguished from one another. A CATEGO re-classification of the cases revealed an 80·2% concordance rate between Kraepelin's diagnoses and ICD-9. Cluster analysis of the original data reproduced closely Kraepelin's dichotomous classification of the psychoses but suggested that DP was a narrower concept than schizophrenia today, while MDI was a composite group including both ‘typical’ manic-depressive illnesses and schizoaffective disorders.

Sir Aubrey Lewis studied 61 depressives in considerable detail, principally cross-sectionally but also by reviewing progress. He concluded that he could find no qualitative distinctions between the depressed patients and thus established himself as a strong and influential advocate of the unitary view of depression (i.e. that depression varies dimensionally, not categorically). Subsequently, Kiloh & Garside (proponents of the binary view of two depressive ‘types’) coded the Lewis data and undertook a principal components analysis. They claimed success in distinguishing ‘endogenous’ and ‘neurotic’ depressive types within Lewis' sample. In this paper we re-analyse the data set using both a latent class categorical approach and mixture analyses. We suggest that any demonstration of sub-types was limited by relative homogeneity of the sample (in that up to 80% had probable or possible psychotic conditions), and by Lewis rating a number of important features (e.g. delusions) dimensionally rather than categorically. Nevertheless, we identify one categorical class (essentially an agitated psychotic depressive condition) and a residual (presumably heterogeneous) class. The presence of those two classes was supported by demonstrating bimodality in composite scores derived from the fourteen differentiating clinical features (and not evident when all clinical features were considered), and formally confirmed by mixture analyses. Membership of the categorical class was determined principally by psychotic features (delusions and hallucinations) and by objectively-judged psychomotor disturbance, and we consider the nature of that ‘class’. Lewis' data set is unusual (in having self-report and observationally rated data), and historically important in demonstrating that conclusions may depend on the choice of variables examined and analytical approaches.

A critical examination is made of the role that statistical methods have played in the understanding of depression. The development of instruments for measuring depression is illustrated by reference to the Beck Depression Inventory and the Hamilton Rating Scale. The controversy over the existence of one or two types of depression is examined from the perspective of the statistical tools used. Some of the problems in studies of the heritability of depression are outlined. The development of clinical trials of depression is examined, with particular reference to ECT and maintenance therapy, and the role of meta-analysis is discussed.

Clinical epidemiology, a term that has been variously defined, is used here to refer to a discipline which, commencing with examination and diagnosis of the individual patient who presents in medical practice, proceeds to study the occurrence of similar, possibly connected cases in the local community, and in so doing may provide hypotheses for population-based studies of disease and its risk factors. While the relevance of this discipline to the modern practice of clinical psychiatry remains largely unexplored, its importance in the search for causes of mental disorder is attested by many instances, both historical and more recent, in which the spread or clustering of psychiatric syndromes in populations could be related to nutritional deficiency, infectious disease, the presence of environmental neurotoxins, the social communication of psychopathology or the transmission of abnormal, harmful behaviour patterns within family groups. Observations made in clinical practice have repeatedly served as the starting point for epidemiological investigation of mental disorders, while conversely epidemiological findings have influenced clinical thinking about their classification, diagnosis, prognosis and morbid risk. A review of the relevant literature underlines the need for a keener awareness of environmental risk factors and a fundamentally epidemiological frame of reference in trying to grapple with the aetiological problems of mental disorder.

Using strict diagnostic criteria, 91 patients with multiple sclerosis (MS) were identified in a defined population of 112000. Of these patients, 29 were found to have been referred to a psychiatrist at least once. Their psychiatric records were searched for cases of MS presenting as a pure psychiatric disorder. Only 18 of the 30 psychiatric referrals before the diagnosis of MS involved purely mental symptoms, and there was no reason to suppose most of them to be related to MS. This study highlighted the problem of how to define a true psychiatric presentation of MS. The uncovering of two likely candidates among a population-based sample of 91 supported the existence of such a phenomenon, but it was concluded that the only way to ascertain how often purely mental symptoms might be the first manifestation of MS would be to conduct a large population-based study with controls.

Family history of Alzheimer's disease (AD) was investigated using a telephone re-interview of 99 cases and 116 controls selected from a case–control study of 170 matched pairs. It was found that the family history method used in the initial interview was satisfactory in identifying first-degree relatives and assessing their ages of birth and death, but the number of first-degree relatives suffering from AD was probably under-estimated. Family history of AD was confirmed as a risk factor for AD. Higher estimates of cumulative incidence were obtained among case relatives than among control relatives. No evidence was found to support the hypothesis that a familial form of AD is more common in those with earlier onset AD (before age 75) in those who display early, prominent features of aphasia or apraxia, or that an AD gene may be sex-linked. The curves for cumulative incidence showed no tendency to reach an asymptote, as is implied by the theory that some forms of AD are due to the action of an autosomal dominant gene. Estimates of lifetime risk by age 90 were within the range found by other investigators. Much larger samples of the very old are needed to obtain estimates of total lifetime risk with smaller standard errors.

Motivated by the lack of knowledge of the pathophysiological processes underlying the manifestation of symptoms in schizophrenia, we have worked out a systematic search strategy. Since epidemiological distribution patterns consistently deviating from expected values provide valuable indications of causal relationships, we chose the higher age of females at first admission for schizophrenia, first reported by Kraepelin and since then confirmed in over 50 studies, as the basis for our study. This unexplained epidemiological finding was replicated on Danish and Mannheim case-register data by systematically controlling for selection and diagnostic artefacts and by testing alternative explanations at the individual stage of the study. To check whether the difference in age at first admission was determined by a difference in age at onset, a representative sample of 267 first-admitted patients with non-affective functional psychosis was examined by using an interview for the retrospective assessment of the onset of schizophrenia (IRAOS) designed for this purpose. Any of the definitions of first-ever onset applied – first sign of mental disorder, first psychotic symptom, first acute episode – led to a significant age difference of 3·2 to 4·1 years between the sexes. The distribution of onsets across the life cycle showed a later increase and a second, lower peak between the ages of 45 and 54 years among females compared with males. The lifetime risk for schizophrenia was equal for males and females. After testing the plausibility of psychosocial versus biological explanations we hypothesized that due to the effect of oestrogens the vulnerability threshold for schizophrenia is elevated in females until the menopause. Animal experiments and post mortem analyses showed that chronic oestrogen applications significantly shortened dopamine-induced behaviour and reduced D2 receptor sensitivity in the brain. The applicability of this pathophysiological mechanism to human schizophrenia was tested on acutely schizophrenic females with normal menstrual cycles. A significant negative correlation was found between measures of symptomatology and plasma oestrogen levels. The manifestation of symptoms in schizophrenia appears to be influenced by a sufficiently sensitive D2 receptor system in the brain, blocked by neuroleptics and modulated by oestrogens.

The effect of gender on mortality was explored for a sample of DSM-III diagnosed schizophrenics followed for up to 42 years. The data for 332 cases and 304 matched normal controls were from the retrospective cohort family studies, the Iowa 500 and non-500. Survival analysis and Cox regression models were used to test the effects of gender, illness status and their interaction on the risks for natural and unnatural deaths. The control men experienced significantly more unnatural deaths than the control women, which was not found for schizophrenic men and women. The unnatural death rate among schizophrenic women was similar to the rate for schizophrenic and control men, and significantly higher than for control women during the early phase of the illness. Findings suggest that some factors that predict suicide may be similar for schizophrenic women and men.

Sex differences in minor psychiatric morbidity (MPM) have been investigated among three aboriginal groups in Taiwan. The study included both ethnographic observation and a sample survey (N = 733) using a modified Clinical Interview Schedule. The findings lend support to the hypothesis that although a female excess of MPM will be found among the patrilineal group (the Bunun), the reverse will be observed in the matrilineal group (the Ami); no such difference will be found in the bilateral group (the Atayal). Further analysis revealed sex differences in the mean duration of MPM and similar incidence ratios between two sexes in these three groups. Possible sociocultural explanations are proposed.

In the last century psychopathologists attached importance to the concept of anhedonia, the loss of ability to experience pleasure. Its role in the diagnosis of melancholia was considered to be crucial. In the present century attention to anhedonia has faded, possibly because of the focus upon depressed mood as the pathognomonic feature of depressive disorders. Research on the symptomatology of endogenous depression did not include the concept; anhedonia was also lacking from the major instruments of psychiatric research, the depression rating scales,

Attention was drawn to anhedonia by two authors: by Meehl in the 1960s and by Klein in the 1970s. Meehl considered anhedonia from the point of view of a personality defect predisposing to mental illness; and Klein regarded anhedonia to be a symptom of depressive illness and probably the best clinical marker predicting response to antidepressant drugs.

In 1980 the revised DSM presented the concept of ‘loss of interest or pleasure’ as one of the two cardinal symptoms of major depression. Since then there has been a gradual recovery of emphasis although many systems confuse the two concepts of‘loss of interest’ and anhedonia. It is possible that anhedonia may provide the key to a more exact delineation of depressive disorders in biological research and in clinical practice. Further research will depend upon a more precise, cross-nationally agreed definition of the concept and the means of its assessment.

One hundred and twenty women recruited from attenders at the antenatal clinic of the Obstetrics Department of a general hospital were asked to complete ad hoc questionnaires during pregnancy; they were then interviewed by psychiatrists using a structured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia (SADS). Nineteen (16%) women were identified as having an onset of an affective disorder during the period of pregnancy, mainly (68%) during the first trimester. As compared with the women without any such onset (controls), the women with pregnancy-related affective disorder (PRAD) were characterized by (1) it being their first pregnancy or first delivery with past termination of pregnancy, (2) early loss of either parent by death, (3) high Eysenck Personality Questionnaire (EPQ) Neuroticism (N) and Psychoticism (P) scores, (4) living in a flat with either a plan to stay there after the forthcoming childbirth or an expectation that their accommodation would be crowded, and (5) negative response to the news of the pregnancy by the husband with low intimacy. The effects of these factors were additive since the probability of developing a PRAD episode was highly correlated with the number of factors reported.

The relationship between traffic noise exposure and psychological morbidity was assessed using the population-based Caerphilly Collaborative Survey of 2398 men from Caerphilly, South Wales. The findings showed that traffic noise exposure levels were strongly associated with annoyance to noise. Noise-sensitive men were more likely to be highly annoyed by noise exposure than less noise-sensitive men. There was no direct association between noise exposure level and psychological morbidity but there were provocative interactions with noise sensitivity. The role of noise sensitivity is discussed as an indicator of vulnerability to environmental stressors and a measure of negative affectivity and over-reporting.

From 686 patients attending primary care physicians, 77 were identified by a screening procedure as having chronic fatigue. Of these, 65 were given a comprehensive psychological, social and physical evaluation. Seventeen cases (26%) met criteria for the chronic fatigue syndrome. Forty-seven (72%) received an ICD-9 diagnosis of whom 23 had neurotic depression, with a further 5 meeting criteria for neurasthenia. Forty-nine were ‘cases’ as defined by the revised Clinical Interview Schedule (CIS-R), and 42 if the fatigue item was excluded. Psychiatric morbidity was more related to levels of social stresses than was severity of fatigue. The main difference between these subjects and those examined in hospital settings is that the former are less liable to attribute their symptoms to wholly physical causes, including viruses, as opposed to social or psychological factors. Identification and management of persistent fatigue in primary care may prevent the secondary disabilities seen in patients with chronic fatigue syndromes.

A mixed retrospective–prospective study of 70 Chinese anorexic patients in Hong Kong shows that although they were similar to Western anorexics in most other ways, 41 (58·6%) of them did not exhibit any fear of fatness throughout their course of illness. Instead, these non-fat phobic patients used epigastric bloating (31·4%), no appetite/hunger (15·7%) or simply eating less (12·9%) as legitimating rationales for food refusal and emaciation. Compared to fat phobic anorexics, they were significantly slimmer pre-morbidly (P < 0·0001) and were less likely to exhibit bulimia (P = 0·001). The possible explanations for the absence of fat phobia and the interpretive dilemma this provokes are discussed from historical, pathoplastic and cultural anthropological perspectives. It is argued that anorexia nervosa may display phenomenological plurality in a Westernizing society, and its identity may be conceptualized without invoking the explanatory construct of fat phobia exclusively. As non-fat phobic anorexia nervosa displays no culturally peculiar features, it is not strictly speaking a Western culture-bound syndrome, but may evolve into its contemporary fat phobic vogue under the permeative impact of Westernization. Its careful evaluation may help clarify the aetiology and historical transformation of eating disorder, foster the development of a cross-culturally valid taxonomy of morbid states of self-starvation, and exemplify some of the crucial issues that need to be tackled in the cross-cultural study of mental disorders.

We describe the existence of the savant syndrome in association with Gilles de la Tourette's Syndrome (GTS). The presentation of savant abilities is typical of that previously described. Similarities between autism, the disorder most characteristically associated with savants, and GTS in terms of obsessionality are noted. Previously reported psychological studies of autistic savants are briefly reviewed and, together with evidence from neuroimaging in GTS, obsessive compulsive disorder (OCD), and autism, used to support a model of the underpinnings of savant skills.

The World Health Organization's study on depressive disorders in different cultures began in 1972. Cohorts of depressed patients were identified in Basle, Montreal, Nagasaki, Teheran and Tokyo. The patients were assessed using standardized measures of social and clinical functioning. Ten-year follow-up data on clinical course, service contact, suicidal acts and social function outcomes were available for 439 (79%) patients. Over one-third (36%) were re-admitted at least once in the follow-up period, half of whom (18%) had very poor clinical outcome. Twenty-four per cent suffered severe social impairment for over half the follow-up period, and over one-fifth (21%) showed no full remissions. The best clinical course (one or two reasonably short episodes of depression with complete remission between episodes) was experienced twice as frequently in patients with a diagnosis of endogenous (65%) as in those diagnosed as suffering from psychogenic depression (29%). Among all patients, a fifth (22%) had at least one episode lasting for more than 1 year, and 10% had an episode lasting over 2 years during follow-up. Death by suicide occurred in 11% of patients, with a further 14% making unsuccessful suicide attempts.

In 1985 a Mood Disorders Unit (MDU) was established at Prince Henry Hospital in Sydney as a clinical research module, linked with the psychiatric department of the University of New South Wales. There were three general objectives: first, to provide a specialized state-wide clinical service for the assessment and management of those with affective disorders, particularly treatment-resistant depression; secondly, to make a research contribution; and thirdly, to serve as an academic centre for teaching and training of undergraduate and postgraduate students from a variety of disciplines.