Previous studies looking for evidence of viral infection in schizophrenics have yielded conflicting results. We searched for viral nucleic acids to test the hypothesis of the viral aetiology of schizophrenia.

We used the polymerase chain reaction (PCR) to search for cytomegalovirus (CMV), human immunodeficiency virus (HIV), influenza A, Borna disease virus (BDV), and bovine viral diarrhoea virus (BVDV) in: hippocampus from three schizophrenic and three non-schizophrenic subjects; cerebrospinal fluid (CSF) from 48 schizophrenic patients; CSF and peripheral blood mononuclear cells (PBMC) from nine sets of identical twins discordant for schizophrenia; and SK-N-SHEP cells co-cultured with schizophrenic and non-schizophrenic brain homogenates. All patients met DSM–III–R criteria.

Virus-specific nucleic acids were not found in any of the samples tested.

The absence of viral nucleic acids in the samples tested suggest that, in these patients, schizophrenia is not associated with a persistent or latent infection due to these viruses.

This is a sociobiological approach to depression using hierarchy and its hypothesised relevance to self-esteem in the marsupial sugar glider (Petaurus breviceps).

Differential access to resources between the dominant and submissive animal is measured by observation in four stable colonies. The dominant animals from two of these colonies are then introduced into the other two, resulting in the transferred former dominants becoming subordinate. Behavioural and biochemical measures relevant to depression and involving access to resources are then repeated. These measures include eating, drinking, social and sexual access, motility, grooming and biochemical estimates of cortisol and testosterone.

Subordinate animals have significantly less access to resources, both in the stable colony and when the formerly dominant animals become subordinate.

A sociobiological approach using a hierarchy model equating resource-holding potential with self-esteem, exemplified by this study, may provide new concepts and insights into the phenomenology and pathophysiology of depression. It allows comparisons to be made between animal behaviour and cognition: the lack of such has been a major difficulty in animal studies hitherto. The findings are possibly more relevant to dysthymia than to affective disorder and imply a relationship between low resource-holding potential in sub-human animals as a phylogenetic antecedent of some of the cognitive and affective aspects of depression in man.

This study explored the psychopathological state of a sample of ‘late paraphrenic’ patients and the reliability of their diagnosis according to the most widely used systems of classification of mental disorders.

The presence and severity of psychiatric symptoms were assessed with the Present State Examination (PSE), the Scale for the Assessment of Positive Symptoms (SAPS), and the High Royds Evaluation of Negativity (HEN) scale. Patient signs and symptoms were classified according to the PSE9–CATEGO4, DSM–III–R, DSM–IV, and ICD–10 diagnostic systems. Agreement among the 11 most widely used criteria for the diagnosis of schizophrenia was assessed for these patients. These included DSM–III–R, DSM–IV, ICD–10, Schneider, Langfeldt, New Haven Schizophrenia Index, Carpenter, Research Diagnostic Criteria (RDC), Feighner, Taylor & Abrams, and PSE9–CATEGO4. The study assessed 47 patients, including in-patients, out-patients, day-patients, and those in the community. Thirty-three elderly controls were recruited from luncheon clubs in Southwark and Lambeth (London, UK).

Patients showed a wide range of delusional ideas, most frequently involving persecution (83.0%) and reference (31.9%). Eighty-three per cent of patients reported some sort of hallucination, most frequently auditory (78.7%). Formal thought disorder was very rare, only one patient showing mild signs of circumstantial speech. No patients exhibited catatonic symptoms or inappropriate affect. Shallow, withdrawn, or constricted affect was found in only 8.5% of patients. The various systems of classification indicated that most patients displayed typical schizophrenic symptoms, although up to one-third of them did not meet criteria for the diagnosis of schizophrenia. There was poor agreement among the different diagnostic schedules as to whether to classify patients as schizophrenic (0.02 < k < 0.45).

Psychotic states arising in late life are accompanied by various psychiatric symptoms that are not entirely typical of early-onset schizophrenia. The current trend to include ‘late paraphrenia’ into the diagnosis of schizophrenia or delusional disorder has poor empirical and theoretical bases.

The prevalence of anxiety disorders in 294 patients who survived to four months in the Perth Community Stroke Study (Perth, Australia), and a follow-up of these patients at 12 months, are presented.

Diagnoses are described both in the usual DSM hierarchic format and by a non-hierarchic approach. Adoption of the hierarchic approach alone greatly underestimates the prevalence of anxiety disorders.

Most cases were of agoraphobia, and the remainder were generalised anxiety disorder. The prevalence of anxiety disorders alone was 5% in men and 19% in women; in community controls, it was 5% in men and 8% in women. Adopting a non-hierarchic approach to diagnosis gave a prevalence of 12% in men and 28% in women. When those who showed evidence of anxiety disorder before stroke were subtracted, the latter prevalence was 9% in men and 20% in women.

One-third of the men and half of the women with post-stroke anxiety disorders showed evidence of either depression or an anxiety disorder at the time of the stroke. At 12 month follow-up of 49 patients with agoraphobia by a non-hierarchic approach, 51 % had recovered, and equal proportions of the remainder had died or still had agoraphobia. The only major difference in outcome between those with anxiety disorder alone and those with comorbid depression was the greater mortality in the latter.

The clinical significance in schizophrenia of positive and negative symptoms at discharge was assessed.

Of schizophrenic patients fulfilling DSM–III criteria, 113 were recruited for this study. Personal, social and psychopathological data were collected and all cases were followed up at one and two years after discharge.

The presence of positive symptoms (64 cases), without concomitant negative symptoms, did not predict the follow-up social function and positive symptom score. Conversely, the presence of negative symptoms (31 cases) predicted worse social functioning (P < 0.05 to P < 0.005) and higher positive symptom scores (P < 0.01) at follow-up using MANOVA. Eighteen cases (15.9%) had neither positive nor negative symptoms and had the best clinical outcome.

Negative, but not positive, symptoms assessed at discharge are an important predictor of poor outcome. In addition, negative symptoms may themselves expose a biological vulnerability to the presence of positive symptoms.

Social mobility among patients with schizophrenia or major affective disorder was compared with that among the general population.

Mobility was studied retrospectively from 1970 to 1987. Socio-economic status (SES) was defined by occupation as in the population census (upper white-collar, lower white-collar, blue-collar, entrepreneur, farmer, unemployed). All patients aged 30–60 years at discharge (2901 men and 3620 women) in 1987–88 in Finland were included in the study. The SES structure of the general population was used for comparisons.

Among patients with schizophrenia there was a constant downward drift, commonly to unemployment. This risk was higher among men than women. In the youngest age group a marked decline from the parents' social status was observed. Among patients with major affective disorder the distribution of SES in 1970 was similar to that of the general population. By 1987, a downward drift was again observed, mainly to unemployment regardless of the initial SES group. The number of patients in occupational categories were usually 30–50% lower than expected.

Schizophrenic patients had a high risk of social drop-out. Among patients with major affective disorder the downward drift was much less.

The effectiveness of different assessment procedures for determining prevalence rates of psychiatric disorder in young adults was investigated.

In a two-stage multi-method procedure, the Young Adult Self-Report, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the Structured Interview for Personality Disorders (Revised), and the Global Assessment of Functioning (GAF) Scale were used to assess prevalence rates in 706 19–24-year-olds from the general population. Furthermore, individuals' subjective perception of distress and referral to mental health services were assessed.

The prevalence of any SCAN/DSM–III–R disorder was 19.3% (95% confidence interval: 11.2–27.4%). Most subjects who received a SCAN/DSM–III–R diagnosis were only mildly impaired. The highest prevalence rates of dysfunctioning (GAF score below 61) without referral to mental health services were for dissociative disorder (2.3%), sleep disorder (2.1 %), alcohol dependence (1.3%) and affective disorder (1.8%).

Instruments that assess functional impairment in addition to DSM–III–R diagnoses are indispensable in prevalence studies.

This study explored the association between ‘late paraphrenia’ and various risk factors such as female gender, sensory impairment, marital status, positive family history of psychoses, and the presence of abnormal neurological signs. It was hypothesised that patients would show significantly more abnormal neurological signs than controls.

Inclusion criteria for the diagnosis of late paraphrenia were fulfilled by 47 patients, including in-patients, out-patients, day-patients, and those living in the community. Thirty-three age-, sex-, education-, and premorbid IQ-matched elderly controls were recruited from luncheon clubs in Southwark and Lambeth (London, UK). A scale for the assessment of neurological soft and hard signs was developed for this study. The Abnormal Involuntary Movement Scale (AIMS) and the Tardive Dyskinesia Rating Scale (TDRS) were also used.

There was a high female-to-male ratio (42:5), and a fourfold increase in the risk of patients having hearing impairment (odds ratio = 4.15, Clodds = 1.36 to 12.63). There was no difference between the two groups in visual difficulties nor in marital status. Patients were approximately ten times more likely to be living on their own (odds ratio = 10.61; Clodds = 3.59 to 31.33) and 16 times more likely to be considered socially isolated (odds ratio = 16.65; Clodds = 5.39 to 51.40). There was no difference between patients and controls in frequency of schizophrenia-like family history. Patients were more likely than controls to exhibit neurological soft signs (z = 4.70; P < 0.001; Cld = 4.61 to 9.63). The presence of abnormal involuntary and tardive dyskinesia movements was associated with the use of antipsychotic medication.

Women appear to run a greater risk of developing late paraphrenia, especially those who are socially isolated and present with associated hearing impairment. The increased presence of neurological soft signs among patients indicates that brain disease may be a critical factor in the development of psychotic symptoms in late life.

Severe cognitive impairment affects many patients with schizophrenia, especially geriatric in-patients. Little is known about the course of this impairment, however.

Two hundred and twenty-four geriatric schizophrenic in-patients were examined for changes in cognitive functioning over a one-year follow-up period, and 45 of them were assessed over a two-year period. In addition, the subset of 45 patients participated in a one-week and one-month test-retest reliability study of the instrument used to assess cognitive impairment, the Mini-Mental State Examination (MMSE).

The average MMSE scores did not change over a one- or two-year follow-up period. The test-retest reliability of the scale was extremely good at both retest intervals.

Among the implications of these data are that cognitive changes in geriatric schizophrenic patients are very slow and are more consistent with a neurodevelopmental process than a neurodegenerative course.

The study tests the hypothesis that juvenile-onset schizophrenia is associated with premorbid developmental impairments. It was predicted that the pattern of developmental impairments would vary with age of onset and with gender.

A case-control design was used to examine developmental impairments in 61 consecutive juvenile-onset (age 7–17) referrals with ICD-9 schizophrenia; 61 non-psychotic psychiatric controls were matched on age and gender. Cases and controls were divided into childhood-onset (age 7–13) and adolescent-onset (age 14–17).

The schizophrenic cases had a significantly higher risk of premorbid social (χ2 = 9.1, P<0.005), motor (χ2 = 9.1, P<0.005) and language impairments (χ2 = 10.1, P<0.005). Specific impairments of language production and comprehension were associated with childhood-onset schizophrenia and were independent of gender.

Juvenile-onset schizophrenia is associated with a range of developmental antecedents. There may be a specific link between cases with a very early onset and an impairment in the processes underlying the development of language.

The mental status examination of an extreme case of longevity, J. C., aged 118 years and 9 months, is documented in order to further knowledge regarding profiles of morbidity in the extremely elderly. J. C. is presently considered to have the longest authenticated life-span in the history of the human species.

Neuropsychological tests were improvised taking into account the subject's severe perceptual deficits. The examination was carried out over a six-month period. A CT scan was also conducted.

The subject's performance on tests of verbal memory and language fluency is comparable to that of persons with the same level of education in their eighties and nineties. Frontal lobe functions are relatively spared and there is no evidence of depressive symptomatology or other functional illness. Cognitive functioning was found to slightly improve over a six-month period.

The subject shows no evidence of progressive neurological disease. A high initial level of intellectual ability may have constituted a protective factor.

Apart from ageing, the factors associated with vulnerability to the emergence of tardive dyskinesia are poorly defined.

Risk factors associated with the presence of a chronic choreic or dystonic disorder were assessed in a cross-sectional comparison of anamnestic and clinical data in a homogeneous group of 64 young psychotic patients (under 40 years of age) on chronic low to moderate doses of neuroleptics.

Dyskinetic subjects presented more indirect indicators of occult brain damage, such as a perinatal event or traumatic brain injuries in infancy and early childhood; neurological examination showed more anomalies in dyskinetic patients than in non-dyskinetics, with a higher prevalence of facial release reflexes.

These data may support the hypothesis that occult acquired brain damage is important in the genesis of this ‘drug-induced’ disorder.

The objective was to examine the relationship between positive life change (PLC) and recovery from depression and anxiety. Following Brown et al (1988, 1992), we hypothesised: (a) that an excess of PLC would be found in the 3-month period before recovery compared with base rates (‘excess hypothesis’) and (b) that fresh-start and anchoring subtypes of PLC would trigger recovery from depression and anxiety respectively (‘specificity hypothesis’).

One hundred and seventy primary care patients with a depressive and/or anxiety disorder, selected from 1994 consecutive attenders, were assessed at baseline and at 1-year and 3.5-year follow-ups on life change (LEDS) and psychopathology (PSE and Course Interview).

Our results appeared to confirm the excess hypothesis regarding depression and anxiety (twofold excess was found prior to recovery), but not regarding mixed anxiety/depression. They did not support the specificity hypothesis.

PLC facilitates recovery but is neither a necessary nor sufficient condition for remission. Difficulty reduction is the most important recovery-enhancing factor.

The efficacy of low doses of certain neuroleptics in improving negative symptoms is still controversial. This study assessed the efficacy of amisulpride, a benzamide which increases dopaminergic transmission at low doses via presynaptic dopamine receptor blockade, on negative symptoms of schizophrenia.

The study was designed as a parallel-group, double-blind, placebo-controlled trial. Patients had to fulfil DSM–III criteria for schizophrenia, Andreasen's criteria for negative schizophrenia, and to have a total score of at least 75 on the SANS; those treated with neuroleptics or antidepressants underwent a six-week placebo wash-out. One hundred and four in-patients were randomly assigned to amisulpride 100 mg/d, amisulpride 300 mg/d, or placebo for six weeks; 85 patients completed the study.

Both amisulpride doses were significantly more effective than placebo on the primary evaluation criterion (SANS total score, MANOVA P < 0.02). No significant changes were found in positive symptoms or in extrapyramidal symptoms.

Negative symptoms can be improved by low doses of amisulpride, favouring the hypothesis of dopaminergic hypofunction as one of the causes of negative symptoms.

The long-term symptom profile of chronic out-patients was studied.

Method. 242 out-patients receiving neuroleptic medications (109 with schizophrenia and 133 non-schizophrenics), were studied for positive (SAPS) and negative (SANS) symptoms at baseline and at 24 months to investigate whether these symptom groups changed over out-patient maintenance treatment.

Overall and within groups, negative symptoms decreased and positive symptoms increased. While the sums of the SANS scores for the schizophrenic patients were initially higher, their mean SANS score dropped more over time (P< 0.001), to show no difference from non-schizophrenics at follow-up. Positive symptoms increased in both groups, although schizophrenics were higher at both times; sub-scales within the SANS showed different patterns of change.

Support is found for a multidimensional view of both positive and negative symptoms and for a reconsideration of the notion of ‘progressive downward course’ in schizophrenia.

We examine the dopamine receptor supersensitivity hypothesis of puerperal psychosis, and explore puerperal changes in the functional sensitivity of this receptor system.

Dopamine receptor sensitivity was estimated using growth hormone (GH) response to apomorphine challenge following delivery in 37 control women, and 11 deliveries in 10 women at ‘high risk’ of puerperal psychosis (previous history of puerperal affective or nonpuerperal manic psychosis). Tests were on days 4 or 5, 11 or 12 and at six weeks postpartum.

Three women developing puerperal psychosis had subsensitive GH responsiveness on day 4. GH response to 67 challenge tests (in control and ‘high risk’ women) increased between days 4 or 5 and six weeks postpartum (P < 0.05). GH response at six weeks correlated with free thyroxine levels (P < 0.01).

These three cases do not support the stated hypothesis. Hypothalamic dopamine receptor sensitivity increases during the puerperium; thyroxine might influence this.

The community-oriented mental illness services providing care to defined populations in south Verona, Italy (17 628 adults) and south Manchester, England (12 021 adults) have been compared to explore relationships between service organisation and patterns of service use.

The composition and function of the two services and the sociodemographic characteristics of the two centres are described and related to epidemiological data on service use in the community, out-patient clinic, day hospital and in-patient care.

Treated incidence of all psychiatric diagnoses and of schizophrenia were significantly higher in south Manchester than south Verona, indicating that the referral filter between primary and secondary care is more permeable in Manchester. Patients known to the service were more likely to be admitted and to have shorter in-patient stays in south Verona, indicating that the filter between in-patient care and the community is more permeable in Verona than Manchester.

The organisation of services in Verona results in a smaller load on the mental health service; the shorter hospital stays can be related to better integration between hospital and community resources. The organisation of services in Manchester provides care for a greater proportion of the population, but would be likely to require increased resources for the mental health services over time.

Clozapine is an effective antipsychotic that has high affinity for serotonin type 2 (5-HT2) receptors. The importance of 5-HT antagonism in the overall clinical efficacy of clozapine is unclear. Using a neuroendocrine strategy we tested the hypothesis that clinical response to clozapine is related to alteration in 5-HT function.

Ten treatment-resistant schizophrenic subjects were treated with clozapine for a mean of 10.3 (s.e. 0.9) weeks; d-fenfluramine (DFEN) challenge tests were performed before and after treatment with concurrent clinical ratings (BPRS, SAPS, SANS) made at the time of testing.

All patients showed clinical improvement following treatment with clozapine. In addition, clozapine produced a significant attenuation of prolactin (PRL) and cortisol (CRT) response to DFEN challenge. Change in symptom ratings correlated significantly with reduction in PRL response to DFEN challenge.

These data show that functional alterations occur in the 5-HT system following response to clozapine and lend support to studies suggesting that 5-HT is an important component to the spectrum of action of clozapine.