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BackgroundNegative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques.AimsTo examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms.MethodA total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart.ResultsWhen comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus.ConclusionsNegative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.

BackgroundThe nature of the relationship between duration of the pre-diagnostic interval in schizophrenia and better outcomes remains unclear.AimsTo re-examine data from one of the earliest studies suggesting an association between long pre-treatment interval and compromised outcome, assessing the relationship between symptomatic and social variables and increased relapse risk at 1 year.MethodSymptomatic, social and demographic data from participants in the Northwick Park Study of First Episodes who completed 12-month follow-up (n= 101) were re-analysed in the context of duration of untreated illness (DUI).ResultsAt admission, those with long DUI were more likely to have lower scores on tension derived from the Present State Examination, exhibited more behaviour threatening to others and more bizarre behaviour, were more likely to be single, to live alone or dependently, to be unemployed and to have experienced more adverse life events prior to admission. Logistic regression showed that diminished tension, bizarre behaviour and unemployed status independently increased the risk of relapse, bizarre behaviour making the single biggest contribution. Tension did not remain significant with log-transformation of data.ConclusionsFindings are consistent with the conclusion that long DUI can reflect characteristics of the psychosis itself rather than delay in treatment.

BackgroundNeuropsychological abnormalities in schizophrenia are well replicated and are present in unaffected relatives. Cognitive findings in bipolar disorder are less clearly established.AimsTo examine the possibility that these abnormalities may provide a means by which the disorders might be separated and to clarify the associations of phenotypic expression and genetic liability.MethodA neuropsychological test battery was administered to 50 control participants, 74 patients and 76 unaffected relatives recruited for the study. Patients included those with schizophrenia from families affected by schizophrenia alone, those with bipolar disorder from families affected by bipolar disorder alone and those with bipolar disorder from families affected by both disorders. Unaffected relatives were also recruited.ResultsCurrent, verbal and premorbid IQ were impaired in people with schizophrenia and in their close relatives. Memory was impaired in all patient and relative groups. Psychomotor performance and performance IQ were impaired in patients, regardless of diagnosis.ConclusionsThis study finds evidence that intellectual abnormalities are related to a genetic liability to schizophrenia. Abnormalities of memory appear to be related to an increased liability to psychosis in general. No impairment was specific to bipolar disorder.

BackgroundThere is growing evidence that schizophrenia is a disorder of cortical connectivity Specifically, frontotemporal and frontoparietal connections are thought to be functionally impaired. Diffusion tensor magnetic resonance imaging (DT–MRI) is a technique that has the potential to demonstrate structural disconnectivity in schizophrenia.AimsTo investigate the structural integrity of frontotemporal and frontoparietal white matter tracts in schizophrenia.MethodThirty patients with DSM–IV schizophrenia and thirty matched control subjects underwent DT–MRI and structural MRI. Fractional anisotropy – an index of the integrity of white matter tracts – was determined in the uncinate fasciculus, the anterior cingulum and the arcuate fasciculus and analysed using voxel-based morphometry.ResultsThere was reduced fractional anisotropy in the left uncinate fasciculus and left arcuate fasciculus in patients with schizophrenia compared with controls.ConclusionsThe findings of reduced white matter tract integrity in the left uncinate fasciculus and left arcuate fasciculus suggest that there is frontotemporal and frontoparietal structural disconnectivity in schizophrenia.

BackgroundHigh-risk’ studies of schizophrenia have the potential to clarify the pathogenesis of schizophrenia. Here, results of extreme outcome groups in the Edinburgh High-Risk Study are presented.AimsTo compare groups of good and poor outcome from the Edinburgh High-Risk Study and clarify the nature of the change from the state of vulnerability to that of developing psychosis.MethodThe recruitment procedure is described. Good and poor outcome are defined. These groups are compared in terms of genetic liability and of baseline and change in neuropsychology and neuroanatomy.ResultsDemographic characteristics and genetic liability do not differ between the groups. The good outcome group perform better at baseline in some neuropsychological tests, but there is little neuroanatomical difference. The poor outcome group show consistently impaired memory function and a tendency to reduction in temporal lobe size.ConclusionsIn genetically predisposed subjects, the change from vulnerability to developing psychosis may be marked by a reduced size and impaired function of the temporal lobe.

BackgroundThe study of high-risk groups and the development of schizophrenia.AimsTo investigate further schizotypy, measured by the Structured Interview for Schizotypy (SIS), and to examine relationships between schizotypal components, psychotic symptoms on the Present State Examination (PSE) and subsequent schizophrenia.MethodThe SIS and PSE were administered on entry. Schizophrenia onsets were recorded during follow-up.ResultsThe SIS yielded four principal components labelled social withdrawal, psychotic symptoms, socio-emotional dysfunction and odd behaviour. On entry, these differentiated between controls, subjects at risk for schizophrenia with and without symptoms and patients with schizophrenia. Seven of 78 subjects at risk developed schizophrenia within 39 months. This was best predicted by combining the four SIS components.ConclusionsSchizotypy is heterogeneous and may become psychosis, particularly if several of its components are present. As psychosis develops, odd behaviour gives way to psychotic symptoms and social function deteriorates.

SummaryThe limitations of current diagnostic categories are well recognised but their rationale, advantages and utility are often ignored. The scientific support for a ‘continuum of psychosis' is limited, and the examination of whether categories, a continuum or more than one continua, and alternatives such as subtypes or hybrid models, best account for the distributions of symptoms in populations has simply not been done. There is a lack of discussion, let alone consensus, about the critical aspects of psychosis to measure, the best ways to quantify those and how these would be applied in clinical practice. Systematic studies are needed to evaluate which of a range of plausible approaches to the classification of psychosis is most useful before change could be justified.

BackgroundIt is reported that people with mild learning disability have a higher point prevalence of schizophrenia than the normal population, the reasons for which are unclear.MethodThirty-nine subjects with mild learning disability and schizophrenia, 34 control subjects with schizophrenia and 28 control subjects with mild learning disability were seen. Interviews with relatives and carers were also conducted. Assessments were made of clinical variables, psychopathology, neurological ‘soft'signs, IQ, memory and family history. Blood was taken for karyotypic analysis from comorbid subjects.ResultsThe comorbid group had more negative symptoms, episodic memory deficits, soft neurological signs, epilepsy and receive more community supports than control subjects with schizophrenia. Comorbid subjects had a tendency to belong to multiply affected families and show high rates of chromosomal variants on routine karyotypic testing.ConclusionsFuture work on the generality of schizophrenia should include people with premorbid learning disability, as a discrete subtype from whom valuable genetic aetiological clues may be obtained.

BackgroundThis second report of a study of service provision for patients with schizophrenia describes patients' contact with general practice and general practitioners' (GPs’) views of the mental health services.MethodA postal questionnaire was sent to the GPs, and patients' primary care records were examined.ResultsData were collected on 131 subjects. The majority of patients (96) (73%) were in regular contact with their GP and were consulting for many different reasons; 27 (21%) were posing particular difficulties for the primary care team. GPs reported that 27 (21%) patients required additional support and that the care arrangements for 50 (38%) patients could be improved if alterations were made to the roles of the professionals already involved.ConclusionsGPs are central to service provision for patients with schizophrenia. Both additional resources and changes in working practices are required to improve patient care. The service implications of these findings are discussed.

BackgroundAlthough poor prognosis has been considered a defining characteristic of schizophrenia, long-term studies show marked heterogeneity of outcome.MethodAssessments of positive and negative symptoms, premorbid and current IQ, and months of in-patient care made in an outcome study of 342 schizophrenic patients were categorised by severity. Determinants of these categorisations were sought from the historical variables available, using analysis of variance. Vignettes of patients with the best and worst symptomatic outcomes were then compared.ResultsNegative symptoms were associated with early onset, male sex and poor academic record. Positive symptoms were associated with occupational decline. Cognitive decline was associated with occupational variables, and in-patient care with academic and occupational variables. The vignettes showed that good outcome was associated with family psychiatric history and poor outcome with unavailability of family history.ConclusionsThe findings support the view that the most malignant form of schizophrenia is neurodevelopmental, but poor outcome was clearly associated with family fragmentation.

BackgroundDetermining the prevalence of psychiatric disorders among remand populations has been made a priority in England and Wales. Differences in legal process and psychiatric services in Scotland make similar research there important.MethodDemographic data were collected on 389 prisoners, the Clinical Interview Schedule was completed and cognitive function assessed.ResultsThe prevalence of major psychiatric disorders was low. Less severe symptoms were more common. The sample was of average IQ, but low educational attainment. Reported drug abuse was high.ConclusionsFew of those interviewed required hospital care, but other symptoms and drug-related problems may place heavy demands on prison medical and psychiatric services.

BackgroundAlthough previous studies have attempted to identify predictors of outcome in schizophrenia, few have prospectively studied first episode patients for an adequate follow-up period.MethodThe psychopathological predictors of outcome were investigated in a subgroup of 51 subjects, originally included in the Northwick Park study of first episode schizophrenia who were followed up 7.3 years (s.d. 1.1, range 5.3– 10.3) after first admission in the Harrow study. Forty-four subjects (24 men, 20 women) were traced. Outcome measures were time to first readmission, occupational level and total duration of hospital admission at five years after first admission.ResultsA survival analysis of time to first relapse revealed that the presence of subjective feelings of depression (CATEGO syndrome SD) during the first admission was associated with early relapse while the presence of depressive delusions (CATEGO syndrome DD) and higher educational attainment protected against early relapse. Total duration of hospitalisation at five years after first onset was positively associated with the presence of CATEGO syndromes SD and OD (biological features of depression) and negatively associated with female sex. Poor occupational outcome was not significantly associated with any psychopathological predictors.ConclusionsOur findings challenge the conventional view that symptoms of depression are associated with better outcome in schizophrenia.

Of 253 patients in their first schizophrenic episode, 52 behaved in a way threatening to the lives of others before their admission to hospital. These 52 patients were studied from data collected at the time of their initial presentation. Despite a history of illness in excess of 1 year in 24 cases, and evidence that violence was motivated by psychotic symptoms in 23 cases, fewer than half of the patients were admitted to hospital as a direct result of their dangerous behaviour. Life-threatening behaviour was more common where the patient had been ill for longer, and where there were delusions of being poisoned.

It has become increasingly apparent that schizophrenic patients can suffer from many cognitive deficits (Hemsley, 1982). These include a decline in IQ (Nelson et al, 1990), loss of concentration (Garmezy, 1978), and various ‘executive’ difficulties similar to those observed in patients with frontal lobe lesions (Morice, 1990). The availability of a large, population-based sample of schizophrenic patients in the Harrow study provided the opportunity to examine the prevalence of these impairments and to relate them to the signs and symptoms of the disorder.

Persisting positive symptoms largely unresponsive to treatment (Tuma & May, 1979; Macmillan et al, 1986; May et al, 1989) occur in about 7% of patients with schizophrenia but lesser degrees of treatment resistance are common (Hogarty, 1988; Johnstone, 1990) and problems of recurrence of positive symptoms and deterioration of negative symptoms are well known (Johnstone, 1990). Schizophrenic patients have also been found to have persisting non-psychotic symptoms, particularly depression (Cheadle et al, 1978). Disorders of movement in relation to schizophrenia and their treatment have been found to be disabling in a few patients and to cause lesser problems for many (Kane et al, 1985). The assessment of the mental state and of clinical evidence of movement disorder in the patients who form the subjects of the Harrow study was therefore clearly of interest, as it is rarely possible to examine these issues in a large, unselected sample.

The social disadvantages for schizophrenic patients in terms of unemployment, impaired relationships, social isolation and downward social drift have been well described (Cooper, 1961; Goldberg & Morrison, 1963; Cheadle et al, 1978; Taylor, 1987). The problems experienced by their caring relatives have been shown to be substantial (Stevens, 1972; National Schizophrenia Fellowship, 1979; Creer et al, 1982). It is important to examine these issues in a large representative sample, and for this reason the social outcome in the 532 patients who form the subjects of the Harrow study of the disabilities and circumstances of schizophrenic patients was examined in some detail.

The aims of this study were to identify and trace all schizophrenic patients discharged from in-patient and day-patient psychiatric services in Harrow between 1 January 1975 and 1 January 1985, to examine the patients in terms of their mental state, cognitive functioning, extrapyramidal function and social disability, and to relate their current status in those terms to demographic, historical and treatment variables. The data collection was conducted between 1 February 1987 and 1 January 1990. The project was devised against the background of developing community care policies for psychiatric patients. In the UK, policies of closure of the mental hospitals have been advocated for a considerable time (Tooth & Brooke, 1961). In the US the plan of closing the mental hospitals and replacing in-patient care with care in the community was partially adopted (Scharfstein, 1978; Fink & Weinstein, 1979; Winslow, 1979). In Italy it was carried out in a much more complete way, at least in some areas (Jones & Poletti, 1985, 1986), but problems appear to have arisen in both of these countries (Donovan, 1982; Papeschi, 1985).

This report concerns 532 patients with schizophrenia. Many items of information have been recorded and the results have been quickly drawn together for publication. It is likely that more detailed analyses of the data will be conducted in time, but this publication reports the central facts derived from this extensive investigation. They can be simply stated. The disorder remains very common. Five hundred and thirty-two individuals with schizophrenia as defined by the Feighner criteria were discharged from Harrow services over 10 years. It was possible to trace the great majority of these patients. In many cases the illness was clearly associated with recurrent or persistent problems. The mean number of admissions required was 5.37 (Fig. 1) and on average patients spent 13.7 of the 120 months between 1975 and 1985 in hospital (Fig. 2).

High mortality rates among schizophrenic patients from infectious diseases, particularly tuberculosis, pneumonia and gastro-enteritis, reported for periods up to the 1940s were shown not to be specific for schizophrenia, but were characteristic of the mental hospital population as a whole (Alstrom, 1942). Studies covering more recent times confirm the decline and virtual disappearance of mortality from tuberculosis (Baldwin, 1979), but an extensive literature continues to emphasise the relatively high mortality of the mentally ill, including those defined as schizophrenic (Innes & Millar, 1970; Tsuang & Woolson, 1977), and more recent record linkage studies (Herrman et al, 1983; Allebeck & Wistedt, 1986) have continued to show an excess of both natural and unnatural deaths. Long follow-up studies of reasonably large groups of well documented cases are relatively uncommon in this area and therefore the 532 cases in the Harrow study were carefully followed up from the point of view of the occurrence and cause of death.

The outcome at two years of patients who were eligible for a study of first schizophrenic episodes was assessed in terms of occupation (n = 237) and in terms of number of days spent as an in-patient from the time of first admission (n = 252), and was related to social, behavioural, mental state and neurological measures during the initial admission. Poor outcome was in general associated with more social withdrawal, inactivity and abnormal social presentation and with more ‘neurological soft signs'. Good occupational outcome in patients with a relatively short pre-treatment duration of illness was associated with the prescription of placebo medication during the follow-up period.

SummaryA masked analysis of videotaped assessments of people at high genetic risk of schizophrenia revealed that those who subsequently went on to develop schizophrenia used significantly more second-person pronouns. This was evident before diagnosis, at two separate assessments approximately 18 months apart. This supports the view that people who go on to develop schizophrenia may have an abnormality in the deictic frame of interpersonal communication – that is, the distinction between concepts being self-generated or from elsewhere may be blurred prior to the onset of a diagnosis of schizophrenia.

In recent years there has been increasing interest in the sociocultural aspects of psychiatric disorders, particularly schizophrenia (World Health Organization, 1975; Sartorius et al, 1986). This has extended from multicentre international studies of prevalence, through national incidence or phenomenological studies in different ethnic groups (Cochrane, 1977; Teggin et al, 1985), to outcome assessments in different cultures (Sartorius et al, 1986, 1987).

Although there has been no truly satisfactory study of the association between antisocial behaviour and psychosis, a variety of sources suggest a greater than chance association between the two (Taylor, 1987), and in particular there is evidence of a substantial increase in violent behaviour in association with schizophrenia (Taylor & Gunn, 1984). There is also evidence of the possibility of over-representation of mentally ill people in arrest statistics, because of an increase in police concern (Teplin, 1985; Taylor, 1987). Studies in this area may concern rates of psychiatric disorder among persons in judicial circumstances (e.g. Taylor & Gunn, 1984), but the Harrow study provided an opportunity of examining the extent and nature of behaviour leading to police contact in a large, unselected sample of schizophrenic patients followed up for up to 13 years.

As part of a study of the contribution of institution-alisation to the disabilities of schizophrenia (Johnstone et al, 1985), all patients fulfilling the St Louis criteria (Feighner et al, 1972) for schizophrenia and discharged from Shenley Hospital between 1 January 1970 and 1 January 1975 were followed up five to nine years later (Johnstone et al, 1981, 1984). Until Northwick Park Psychiatric Unit opened in 1975, psychiatric facilities for Harrow patients were all in Shenley Hospital. In the follow-up study the patients were examined in detail and an account of their social circumstances and functioning was obtained. It was considered that the study provided an opportunity to examine the success of community care in a group of schizophrenic patients who left hospital before very active policies of discharge for such patients had been developed. The results had both positive and negative aspects. For example, 18% of the patients examined had recovered to the extent that they had no significant symptoms and appeared to function satisfactorily, but more than 50% had definite psychotic features. No patients and few relatives sought a return to in-patient care, but severe emotional, social and financial difficulties were commonplace. Moreover, 27% of the sample had no contact with the medical or social services.

SummaryStudies of face processing have begun to elucidate the brain regions involved in social cognition, which include frontal and temporal regions known to be reduced in volume in schizophrenia. In this case-control study participants with schizophrenia (n=20) showed marked deficits in their ability to interpret social cues from faces, and those experiencing positive symptoms were impaired in recognising even basic facial emotions.

SummaryFive hundred and ten patients receiving long-term in-patient care for schizophrenia were examined in terms of their current mental state, cognitive functioning, neurological status and behavioural performance. The abnormalities of these areas of their present state were related to historical factors, personal details, the features of the illness at its worst and physical treatment received. Significant associations between the present state and historical factors were few and mainly concerned time and the features of the illness at its worst. Current abnormalities were not related to past physical treatment, but highly significant correlations were found between the impairments of the four areas of the present state. It is concluded that these impairments are likely to be an integral part of the disease.

Gastrointestinal permeability was assessed by means of absorption of 51Cr-labelled EDTA in 24 patients with schizophrenia (12 in relapse and 12 in remission). The results were compared with those for patients with coeliac disease and those for normal controls. Significant differences between the schizophrenic patients and the normal controls were not established. The results for the schizophrenic patients in remission were no different from those for the patients in relapse, and there was no evidence from the study of an effect on gastrointestinal permeability of either anticholinergic or antidepressant medication. It is concluded that schizophrenia is, at least in the majority of cases, unrelated to coeliac disease.

Gastrointestinal permeability was assessed by means of absorption of 51Cr-labelled EDTA in 24 patients with schizophrenia (12 in relapse and 12 in remission). The results were compared with those for patients with coeliac disease and those for normal controls. Significant differences between the schizophrenic patients and the normal controls were not established. The results for the schizophrenic patients in remission were no different from those for the patients in relapse, and there was no evidence from the study of an effect on gastrointestinal permeability of either anticholinergic or antidepressant medication. It is concluded that schizophrenia is, at least in the majority of cases, unrelated to coeliac disease.

The mental states of 92 inpatients with chronic schizophrenia were assessed on two occasions 4 years apart. The relationship between the two ratings was examined in the 84 patients who were either consistently on or consistently off neuroleptics. Negative features were more stable than positive, but were not irreversible. Every feature examined was shown to resolve in some cases.

SummaryPlatelet MAO activity was assessed in 35 schizophrenics during a trial of the isomers of flupenthixol. Enzyme activity was unrelated to severity of symptoms, the presence of delusions, hallucinations or thought disorder or to negative symptoms. In a few patients MAO activity fluctuated widely with time, but in the group of patients on medication there was a slow decrease in enzyme activity which was significant after 28 days of treatment. Enzyme activity after 14 days' drug treatment was still correlated with activity before treatment, but after 28 days this significant correlation disappeared. Slow effects of neuroleptic drugs on platelet MAO activity may explain previous findings of reduced activity of the enzyme in schizophrenia.

SummaryThe hormonal effects of apomorphine, a direct-acting dopamine receptor agonist, in schizophrenic patients are of interest in view of the therapeutic efficacy of dopamine receptor antagonists. In this study, apomorphine (0.75 mg s.c.) and placebo were administered to unmedicated acute and chronic schizophrenics and controls. Apomorphine-induced prolactin suppression did not discriminate between the groups. However, an inverse relationship between basal prolactin levels and the severity of positive symptoms was detected in the patients with acute schizophrenia, consistent with a role for dopamine in the genesis of these symptoms. Growth hormone increments after apomorphine administration were blunted in the chronic schizophrenic patients, particularly those with ‘negative’ symptoms. It is argued that this blunting is not due to previous neuroleptic therapy and may represent evidence of structural change in the hypothalamus in this group of patients.

Of 253 patients from nine medical centres identified with first episodes of schizophrenic illness, 17 did not achieve discharge during the period of trial recruitment. 120 entered a randomised controlled trial of neuroleptic medication and were followed-up, as were 116 who were eligible for the trial but did not enter it. Overall, 60% of the sample had relapsed within two years of discharge; age, sex, ethnic origin, duration of admission, social withdrawal before admission, and type of onset of illness were not significantly related to relapse. Relapse rates were lower on active trial or standard medication than placebo, but however assessed, outcome at this early stage was poor for many patients.

SummaryThe outcome in clinical and social terms of a psychiatric illness arising within 1 year of confinement or termination of pregnancy and requiring on-going care was studied after a period of 1–6 years in 47 women. The outcome was related to the earlier features of the illness and to personal and historical features. Social impairment and continuing psychopathology occurred in many cases. The only factor which significantly related to poor outcome was an initial diagnosis of schizophrenia.

The activities of the A and B forms of the enzyme monoamine oxidase (MAO, E.C. 1.4.3.4) have been assessed with the substrates 5-hydroxytryptamine and benzylamine respectively in seven areas of the brains of 39 patients with schizophrenia and 44 control subjects. Whereas previous studies have found the enzyme unchanged in brain in schizophrenia, in this study there was a modest but significant decrease in the activity of MAO-B in frontal and temporal cortices and in amygdala. This decrease could not be accounted for by neuroleptic medication, age, sex or post-mortem variables. In a series of 22 patients who had been assessed in life, the reduction in MAO-B activity was found to be associated specifically with the presence of negative symptoms (flattening of affect and paucity of speech). The findings are therefore consistent with other evidence for structural and neurochemical change in the temporal lobe that have been associated with the type II (defect state) syndrome of schizophrenia. The change in enzyme activity is unlikely to be related to a change in monoamine metabolism but may reflect a disturbance in glial function. The change in MAO-B activity in brain in this study is confined to particular areas of brain and a subgroup of patients; it is thought to be entirely unrelated to earlier reports of reductions of enzyme activity in platelets, which are probably attributable to prolonged neuroleptic medication.

It has become customary to classify the typical abnormalities of the mental state of schizophrenic patients into positive and negative features, with reference to behavioural excesses and deficits. Positive features are pathological by their presence and negative features represent the loss of some normal function. Positive features are generally considered to include delusions, hallucinations and positive formal thought disorder (Fish, 1962). Some studies (e.g. Johnstone et al, 1978) have also included incongruity of affect under this heading. Negative features include affective flattening, poverty of speech, retardation, apathy, lack of sociability. There is some evidence that the clinical correlates of positive and negative features may not be the same (Owens & Johnstone, 1980). Some workers (Andreasen & Olsen, 1982) but not others (Pogue-Geile & Harrow, 1984) have found that among schizophrenic patients positive and negative symptoms were negatively correlated. Although the nature of the relationship between positive and negative features is not entirely established and may not be simple (Wing, 1978) certain generalisations may be applied: (a)Positive features are characteristic of earlier and negative of later phases of the illness (Pfohl & Winokur, 1982).(b)The effects of drugs upon positive features are greater than those upon negative features. Thus neuroleptics produce more marked improvement (Johnstone et al, 1978; Angrist et al, 1980) and amphetamine more marked exacerbation (Angrist et al, 1980) of positive than of negative features.(c)Positive features have been said to be relatively variable and negative features relatively stable (Ovchinnikov, 1968; Snezhnevsky, 1968).

Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness, 120 entered a randomised placebo-controlled trial of maintenance neuroleptic medication on discharge; they were followed to relapse or loss to follow-up, for two years or to the end of the study. Of those on active medication, 46% relapsed, as did 62% of those on placebo; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication. This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis, or because susceptibility to relapse is reduced by early institution of treatment. The study provides no data on which a decision between these alternative explanations can be based.