Neuroleptics are structurally a heterogenous group of compounds which possess antipsychotic activity. They increase dopamine metabolites by blocking dopamine receptors and enhancing presynaptic turnover. This forms the cornerstone of the dopamine hypothesis of neuroleptic action, which is supported by wide-ranging behavioural, physiological and biochemical studies. It is, however, clear that neuroleptics are far less specific for the dopamine receptor than was previously considered. They influence a range of neuronal activities, including calcium-activated potassium conductance, which governs the rate of action potential generation by many neurones. Recent physiological studies indicate that all commonly used neuroleptics alter calcium-activated potassium conductance in central neurones, in concentrations similar to those achieved clinically. An adaptive increase in calcium-activated potassium conductance mechanisms in key sensory processing neurones would render the psychotic patient less susceptible to bombardment by environmental stimuli. This action may explain in part the therapeutic effect of neuroleptics.

A group of 118 patients with a hospital diagnosis of schizophrenia was reviewed. The incidence of suicide attempts was significantly correlated with more frequent past psychiatric admissions, more frequent past diagnoses of schizophrenia, and poor work function. The apparent relationships could be spurious or based on a reversed causal sequence; for example, suicide attempts are likely to be followed by psychiatric admissions.

Common neurotic and personality disorders account for widespread personal restriction and suffering. The need for effective, economically feasible treatment methods is widely acknowledged and the range of conditions successfully treated by available methods needs to be established. This study is concerned with two methods of brief psychotherapy; our aim was the essentially pragmatic one of investigating how far relatively long-term NHS out-patients with neurotic, personality, and interpersonal problems could be successfully and economically treated by the kind of therapists available in NHS settings. It is generally believed by psychoanalytically-oriented therapists that brief therapy requires high levels of training and experience; this is tested here, in that all the therapies were strictly time-limited, and none of the therapists had completed advanced training.

Volume measurements were carried out on 29 brains from institutionalised, chronic schizophrenic patients and 30 age and sex-matched controls using a stereological method. The volumes of the total fixated brain, the hemispheres, the cortex, and the central grey matter of the schizophrenic brains were significantly reduced while the volumes of the ventricles were significantly enlarged compared with the control group. The patients had been diagnosed by a psychiatrist on the basis of their case records as having either a Type I or Type II syndrome according to the symptoms they presented in the first years of their disease. The Type II patients were found to have significantly enlarged ventricles compared with the Type I patients.

The Copenhagen longitudinal high-risk study of offspring of 129 schizophrenic mothers commenced in 1962. At that time, the mothers were diagnosed according to contemporary Danish criteria. We have re-examined all of the hospital records of these mothers: 108 (84%) fulfil present-day DSM-III criteria for schizophrenia and 95 (74%) were diagnosed as paranoid schizophrenic according to ICD-8 criteria. In a follow-up at mean age 24, the offspring of the paranoid schizophrenic mothers were themselves found to be less frequently schizophrenic (5%) than were the offspring of non-paranoid schizophrenic mothers (29%).

Dinan's paper seeks to question the validity of the now widely accepted hypothesis that neuroleptic drugs of various different chemical categories all act by a common mechanism, namely by blockade of dopamine receptors of the D2 type in brain (for review see Creese et al, 1978, 1983; Iversen, 1985). While it is always refreshing to re-examine existing scientific dogma, his criticisms did not appear to me to be very substantial. Having quite fairly reviewed the evidence in favour of the “dopamine hypothesis” for neuroleptic drug action, Dinan summarises his reasons for questioning it. He points out that many neuroleptic drugs have potent actions on a number of other targets, apart from the dopamine receptors in brain. This is indeed so, and the archetypal compound, chlorpromazine, has a particularly rich spectrum of pharmacological activity, being a potent antagonist of serotonin (5-HT2) receptors, ?-adrenoceptors, and histamine (HI) receptors in brain and other tissues. Other neuroleptics also have potent actions on a number of other systems. Indeed, if one were to have studied only chlorpromazine, it is doubtful whether the “dopamine hypothesis” could ever have been developed. The strength of this hypothesis lies in the fact that of all the diverse pharmacological actions which different neuroleptic drugs exhibit, this is the only action that is common to all neuroleptic compounds. Furthermore, in a large group of neuroleptics, which differ widely in potency (doses in man ranging from 1 mg/day to almost 1000 mg/day), the potencies of these drugs as dopamine (D2) antagonists correlate significantly with their clinical potencies. Attempts to make such correlations with any other known pharmacological properties of these drugs fail to show significance (Creese et al, 1978, 1983).

We conducted a one-year follow-up of patients who had made a first contact with psychiatric services in Chandigarh, North India, and had been assigned a diagnosis of schizophrenia. The expressed emotion (EE) of the patients' relatives was assessed early on. We found the same associations between the individual components of EE and relapse of schizophrenia as in previous Anglo-American studies, but only the association between hostility and relapse was statistically significant. Applying the same criteria as in the Anglo American studies for ‘high EE’, we found a significant relationship between high EE and relapse. This relationship was not explained by other factors often associated with higher relapse rates. We conclude that the significantly better outcome of Chandigarh first-contact patients compared with a London sample is largely due to the significantly lower proportion of high-EE relatives in the North Indian sample.

Consecutive new patients presenting at a Nigerian psychiatric unit over a 14-month period and fulfilling the DSM-III criteria for schizophreniform disorder, (active) schizophrenia and residual schizophrenia were studied. There were no differences between the three groups with respect to background social data. The schizophreniform patients had a lower incidence of previous psychotic episodes. There were no differences between the first two groups with respect to the distribution of PSE symptoms and signs, Schneider's First Rank Symptoms, or severity of psychopathology. Initial clinical outcome, and longer-term clinical and social outcome, assessed 25–38 months after index presentation, was best in the schizophreniform patients and worst in the patients with residual schizophrenia. The findings are consistent with schizophreniform disorder lying on a spectrum of schizophrenic disorders. They also highlight inadequacies in mental health services in Nigeria and other developing countries.

Re-analyses of data presented by Macmillan et al (1986b) challenge their conclusions that high expressed emotion is not prognosticate significant for the course of schizophrenia or unrelated to the level of behavioural disturbance prior to admission. Several equally plausible models of causal relationships between EE and duration of untreated illness are presented. We conclude that our re-analyses of the Macmillan data do not warrant premature closure regarding the significance of the EE variable.

A historical review of suicide in Fiji shows that rates for people of Indian descent have always been higher than those of other groups, yet until now this phenomenon has attracted little official or public attention. Recent changes in the incidence and methods of suicide have led to the introduction of some preventive measures, but the emphasis has been on eliminating some of the methods rather than the reasons for suicide. The continuing high incidence of suicide by hanging involving some sectors of society appears to have been overlooked. Possible causes of this apparent lack of interest are examined, such as the low status historically of Indian immigrants and concepts held about them by other groups in Fiji, and the ‘invisibility’ of groups of people such as rural women and the aged.

Karl Popper has taught us that no hypothesis can be regarded as proved-merely as having survived the most stringent tests which have so far been devised. Dinan makes a further attempt to overthrow the dopamine hypothesis of the mechanism of the antipsychotic effect, and provides an alternative suggestion. As one time critic and later advocate of the theory, I think he underestimates its explanatory power and capacity for survival. I doubt that his alternative yet poses a serious challenge. I propose below a second (and perhaps more idiosyncratic) alternative. I do not claim it yet has the explanatory power of the dopamine theory, but I think it generates some new approaches.

Attempts were made to identify, and include in a two-year follow-up study, every patient living in the catchment area of the Mapperley group of psychiatric hospitals in Nottingham (population 390 000) who made their first-ever contact with the psychiatric services for a potentially schizophrenic illness during a two-year period (1 August 1978 to 31 July 1980). Screening was based upon symptoms rather than diagnosis, covering both in-patient and out-patient services; a consensus diagnosis using ICD-9 was made by the project team. The Nottingham Psychiatric Case Register was used in a retrospective Leakage Study which added nine cases to the 99 identified by the screening procedures. Incidence rates are given for both broad and narrow concepts of schizophrenia, and for DSM-III diagnosis. The Nottingham incidence rates are similar to those reported from other UK centres, and are near the middle of the range found in the other collaborating centres in the WHO study on Determinants of Outcome of Severe Mental Disorders. At entry to the study, 27 patients were out-patients, and 11 were never admitted to hospital at any time in the two-year follow-up period. Reasons for believing that the Nottingham administrative incidence may be close to the incidence in the community are discussed.

In the preceding paper, Mintz et al have raised a number of criticisms and points relating to our study, to which we are pleased to respond.

Variations in clinical features associated with unemployment among a sample of male parasuicides were examined. Employed and unemployed persons did not differ in mean scores on the Suicidal Intent Scale, but the unemployed were rated significantly worse on measures of depression (Beck Depression Inventory) and hopelessness (Hopelessness Scale). A covariance analysis showed that hopelessness, rather than depression, is the important discriminator. Different patterns of relationships between the three clinical measures were observed in the two groups. Hopelessness may be a key social-psychological variable for inclusion in any model of the pathways which link unemployment with parasuicide.

Expressed emotion ratings were performed, in two separate settings, on the parents of 20 children suffering from anorexia nervosa. Ratings were made on conventional individual interviews and on videotapes of a family interview. Comparison of ratings in the two settings showed a very high correlation for ‘critical comments'. Findings on the other scales were harder to interpret, but significant correlations as well as differences were noted. Expressed emotion rated in family interviews provides new possibilities for the study of families.

A 21–27-year follow-up was conducted on 140 schizophrenic patients consecutively discharged from the Department of Neuropsychiatry, Gunma University Hospital, between 1958 and 1962, and 130 patients (93%) were successfully evaluated. Of these patients, 105 were still living, and the longitudinal courses could be fully observed in 98. With regard to the social outcome of the 105 patients, 47% were assessed as 'self-supportive’ whereas 31% were ‘hospitalised‘. As for psychopathological outcome, 31% were ‘recovered’, 46% were ‘improvead’, and 23% were ‘unimproved‘. In the studies of the longitudinal courses of the 98 patients, fluctuating courses of social adjustment were the most numerous in the early stages, whereas in the later stages many of the patients showed differentiation in one of two directions, namely the 'stable self-supportive’ state and the ‘chronic institutionalised’ state. However, this form of differentiation was not revealed in the distribution of psychopathological ‘end states'.

The psychopathology of acute organic psychosis was investigated by interviewing 74 patients using the Present State Examination (PSE). Their delusions, perceptual disturbance, thought disorder, and emotional disorder were categorised and then compared with those seen in 74 acute schizophrenics. In acute organic psychosis there was a particular pattern to the delusions, perceptual disturbance, and thought disorder, which was quite unlike that seen in acute schizophrenia. These results have implications for theories claiming that schizophrenia is an organic psychosis. It is suggested that the psychopathology in acute organic psychosis has very different origins from that seen in schizophrenia.

The timing and number of recent stressful life events occurring in the year before onset of emotional or behavioural disorder was examined in a consecutive sample of children. Overall, events increase the relative risk of psychiatric disorder by 3–6 times. Events occur throughout the 12 months, but tend to cluster in the 16 weeks nearest onset of symptoms. The number of events influences the onset of disorder: cases with multiple events are more likely to have an event within 16 weeks of onset; cases with single events are more likely to have the event 36–52 weeks before onset. Cases whose onset occurs within 4 weeks of an event may have experienced single or multiple events. The results support the concept of additivity of recent stressful events in some cases of emotional and behavioural disorders in childhood.

The 800 census enumeration districts of Nottingham were used as a basis for the production of 12 distinct ‘clusters’ or neighbourhood types. Plotting the place of residence of the 68 patients with ‘certain’ or ‘very likely’ diagnoses of ICD-9 schizophrenia, identified in the World Health Organization Study of Determinants of Outcome of Severe Mental Disorders, showed the expected concentration in central areas of low social status. A more varied distribution was found for 132 patients with a case-register diagnosis of affective psychosis, contacting the psychiatric services for the first time during the same two-year period as the schizophrenic patients. Some of the highest rates for affective psychosis were found in new housing estates of middle and low status at some distance from the town centre.

A computerised diagnosis, AGECAT, is applied to data from random community samples of the elderly in New York and London in order to examine the prevalence of mental illness in the two cities, especially the result reported from the same study, using a different diagnostic procedure, that the proportion of dementia was higher in New York. The greater proportion of dementia in New York is confirmed for all AGECAT's levels of diagnostic confidence, for both sexes and at all half-decades over 65 years. Provided that this difference is upheld and genetic differences can be discounted, these findings would seem to support a contributory environmental cause for dementia. Proportions of depression as a whole are similar in both cities. Syndrome case and sub-case levels of neurotic disorder are generally higher in London.