Is the incidence of psychotic disorder in decline? Epidemiological evidence from two decades of research.

BACKGROUND: It is unclear whether the incidence of first episode psychoses is in decline. We had the opportunity to determine whether incidence had changed over a 20-year period in a single setting, and test whether this could be explained by demographic or clinical changes. METHODS: The entire population at-risk aged 16-54 in Nottingham over three time periods (1978-80, 1993-95 and 1997-99) were followed up. All participants presenting with an ICD-9/10 first episode psychosis were included. The remainder of the population at-risk formed the denominator. Standardized incidence rates were calculated at each time period with possible change over time assessed via Poisson regression. We studied six outcomes: substance-induced psychoses, schizophrenia, other non-affective psychoses, manic psychoses, depressive psychoses and all psychotic disorders combined. RESULTS: Three hundred and forty-seven participants with a first episode psychosis during 1.2 million person-years of follow-up over three time periods were identified. The incidence of non-affective or affective psychoses had not changed over time following standardization for age, sex and ethnicity. We observed a linear increase in the incidence of substance-induced psychosis, per annum, over time (incidence rate ratios: 1.15; 95% CI 1.05-1.25). This could not be explained by longitudinal changes in the age, sex and ethnic structure of the population at-risk. CONCLUSIONS: Our findings suggest psychotic disorders are not in decline, though there has been a change in the syndromal presentation of non-affective disorders, away from schizophrenia towards other non-affective psychoses. The incidence of substance-induced psychosis has increased, consistent with increases in substance toxicity over time, rather than changes in the prevalence or vulnerability to substance misuse. Increased clinical and popular awareness of substance misuse could also not be excluded.

Aggressive incidents in first-episode psychosis.

BACKGROUND: Recent research has reported increased risk of aggressive incidents by individuals with psychotic illness. AIMS: To examine acts of aggression in first-episode psychosis. METHOD: Subjects with a first-episode psychosis were ascertained from a defined catchment area (Nottingham, UK) and reassessed at 3 years (n=166) using clinical interview, informants, health care and forensic records. RESULTS: Of the subjects, 9.6% demonstrated at least one act of serious aggression (defined as weapon use, sexual assault or victim injury) during at least one psychotic episode and 23.5% demonstrated lesser acts of aggression (defined as all other acts of aggression). For all aggressive subjects (33.1%), unemployment (OR=3.6, 95% C11.6-8.0), comorbid substance misuse (OR=3.1, C1 1.1-8.8) and symptoms of overactivity at service contact (OR=6.9,C1 2.7-17.8) had independent effects on risk of aggression. CONCLUSIONS: We confirmed some previously reported demographic and clinical associations with aggression in first-episode psychosis but no relationship with specific psychotic symptoms or diagnostic groups was observed.

The functional anatomy of auditory hallucinations in schizophrenia.

We used continuous whole brain functional magnetic resonance imaging (fMRI) with a 3-T magnet to map the cerebral activation associated with auditory hallucinations in four subjects with schizophrenia. The subjects experienced episodes of hallucination whilst in the scanner so that periods of hallucination could be compared with periods of rest in the same individuals. Group analysis demonstrated shared areas of activation in right and left superior temporal gyri, left inferior parietal cortex and left middle frontal gyrus. When the data were examined on an individual basis, the temporal cortex and prefrontal cortex areas were activated during episodes of hallucination in all four subjects. These findings support the theory that auditory hallucination reflects abnormal activation of normal auditory pathways.

Three-year outcome of first-episode psychoses in an established community psychiatric service.

BACKGROUND: Changes in service provision, secular trends in substance misuse and changing social structures might affect outcome in psychosis. AIMS: To assess the three-year outcome of an inception cohort of first-episode psychoses treated in a modern, community-oriented service; to compare outcomes with an earlier cohort treated in hospital-based care; and to examine the predictive validity of ICD-10 diagnostic criteria. METHOD: Three-year follow-up (1995-1997) of an inception cohort of first-episode psychoses and comparison with two-year follow-up (1980-1982) of the Determinants of Outcome of Severe Mental Disorders (DOSMED) Nottingham cohort. RESULTS: On most outcome measures, non-affective psychoses had a worse outcome than affective psychoses. Affective psychoses had better outcome than previously reported. Substance-related psychoses had very poor occupational outcome. Similar proportions of the current and DOSMED cohort were in remission but the former were rated as having greater disability. CONCLUSIONS: In a modern community service, 30-60% of patients with first-episode psychoses experience a good three-year outcome. The ICD-10 criteria have good predictive validity.

Prevalence of substance misuse in first-episode psychosis.

BACKGROUND: Reports suggest a high prevalence of substance misuse in psychotic disorders but few studies examine comorbidity at onset of psychosis. AIMS: To identify the prevalence and pattern of substance use and misuse in first-episode psychosis, and relationships with diagnosis, mode of presentation and demographic variables. METHOD: Consensus diagnoses for 168 subjects presenting with first-episode psychosis were made using ICD-10 diagnostic criteria. Information on substance use and misuse was obtained from multiple sources. We examined associations between substance misuse, diagnosis and demographic factors. RESULTS: Criteria for drug use, drug misuse or alcohol misuse were met by 37% of the sample. One-year prevalence rates were 19.5% (drug misuse) and 11.7% (alcohol misuse). Thirteen subjects (8.4%) received a primary diagnosis of substance-related psychotic disorder; a significant increase compared with an earlier cohort from the same catchment area. Drug misuse was associated with younger age of onset of psychosis, male gender and non-African-Caribbean ethnicity. CONCLUSIONS: This study confirms high rates of substance misuse at onset of psychosis. There is evidence for an increase in diagnosis of substance-related psychotic disorders over time. Those most at risk of substance misuse are young males.

Diagnostic stability of first-episode psychosis. Comparison of ICD-10 and DSM-III-R systems.

BACKGROUND: The temporal stability of a diagnosis is one measure of its predictive validity. AIMS: To measure diagnostic stability in first-episode psychosis using ICD-10 and DSM-III-R. METHOD: Between 1992 and 1994 we ascertained a cohort of persons with first-episode psychosis (n = 168), assigning to each a consensus diagnosis. At three-year follow-up, longitudinal consensus diagnoses, blind to onset diagnoses, were made. Stability was measured by the positive predictive values (PPVs) of onset diagnoses. For onset schizophrenia, we also calculated sensitivity, specificity and concordance (kappa). RESULTS: First-episode ICD-10 and DSM-III-R schizophrenia had a PPV of over 80% at three years. Over one-third of cases with ICD-10 F20 schizophrenia at three years had non-schizophrenia diagnoses at onset. Manic psychoses showed the highest PPV (91%). For onset schizophrenia, both systems had high specificity (ICD-10: 89; DSM-III-R: 93%), but low sensitivity (ICD-10: 64%; DSM-III-R: 51%) and moderate concordance (ICD-10: 0.54; DSM-III-R: 0.46). CONCLUSIONS: Bipolar disorders and schizophrenia showed the highest stability. DSM-III-R schizophrenia did not have greater stability than ICD-10 schizophrenia.

Evaluating the Health of the Nation Outcome Scales. Reliability and validity in a three-year follow-up of first-onset psychosis.

BACKGROUND: The HoNOS has been developed as a routine measure of outcomes in mental health. AIMS: To explore the validity and interrater reliability of HoNOS in a first-onset psychosis follow-up study. METHOD: Between 1992 and 1994 we ascertained a cohort of all persons with first-onset psychosis. We re-assessed these people at 3 years (n = 166) with several outcome scales, including HoNOS. Patients' keyworkers also completed the HoNOS. We estimated concurrent validity by calculating correlations between HoNOS and other scales, and interrater reliability. RESULTS: Researcher HoNOS correlated highly with other scales (0.46 < p < 0.86; P < 0.001). Keyworker HoNOS correlations were lower (0.41 < p < 0.51; P < 0.05), but still significant for all scores except the HoNOS-social subscale (0.12 < p < 0.28). Agreements between researcher and keyworker HoNOS were modest (0.47 < ICC < 0.85). CONCLUSIONS: In this research cohort HoNOS correlates well with established outcome scales. Keyworker ratings show similar, but weaker, relationships; its use in routine settings may require further training for calibration of severity.

Incidence of schizophrenia in Nottingham. A comparison of two cohorts, 1978-80 and 1992-94.

BACKGROUND: Several studies have reported a decline of up to 50% in the incidence of schizophrenia over recent decades. We aimed to measure changes in the incidence and diagnostic patterns of first-episode psychosis by comparing two Nottingham cohorts, identified in two equal periods separated by 14 years. METHOD: Two prospectively ascertained cohorts of first-episode psychotic disorder were identified over the time periods 1978-80 and 1992-94. The earlier cohort was of the World Health Organization Determinants of Outcome of Severe Mental Disorder (DOSMD) ten-country study. The later cohort was obtained using similar methodology. Both groups were diagnosed using ICD-10 diagnostic criteria and age-standardised incidence rates were compared. RESULTS: The standardised incidence rate for all psychotic disorders rose slightly from 2.49 to 2.87 per 10000 population per year, but the F20 classification fell significantly by over a third (1.41 to 0.87 per 10000 per year). The second study group (1992-1994) included a greater diversity of psychotic diagnoses compared with the first, in particular an increased proportion of acute and drug-related psychoses. CONCLUSIONS: Methodological considerations call for caution in interpreting such data, but we conclude that the significant fall in the narrowly defined diagnostic category of schizophrenia reflects a real change in the syndromal presentation of psychotic disorders.

Increased incidence of psychotic disorders in migrants from the Caribbean to the United Kingdom.

BACKGROUND: Several studies have replicated the finding of increased incidence of schizophrenia and related psychoses in first and second generation migrants from the Caribbean. The finding has remained consistent in studies employing different methods, but concern has been expressed about indirect methods of calculating the population at risk. This study aims to overcome these short-comings. METHOD: A further prospective study was undertaken in Nottingham assembling an inception cohort of psychotic patients (N = 168) presenting from a defined catchment area. The 1991 census, which includes codings for self-ascribed ethnic origin, was used to calculate the denominator, employing correction factors for potential under-enumeration. Case-ascertainment was based upon all service contacts and subjects had in-depth assessments including the SCAN. Collateral history was obtained from informants. RESULTS: Subjects born in the Caribbean, or who had one or both parents born in the Caribbean, had a greatly elevated risk (incidence ratios above 7) for all psychotic disorders and for ICD-10 (DCR)-defined F20 Schizophrenia. CONCLUSIONS: The size of the increase and the methodological safeguards employed support the validity of this now highly replicated finding. A personal or family history of migration from the Caribbean is a major risk factor for psychosis; the consistency of this finding justifies a systematic evaluation of potential aetiological factors. Any hypothesis derived from the evidence so far must explain: increased incidence in first and second generation migrants; increased risk for all psychoses (including affective psychoses); and an effect specifically associated with a migration history from the Caribbean to Northern Europe.

The predictive validity of a diagnosis of schizophrenia. A report from the International Study of Schizophrenia (ISoS) coordinated by the World Health Organization and the Department of Psychiatry, University of Nottingham.

BACKGROUND: Outcome is important in the validation of psychiatric diagnosis, as most disorders lack clinicopathological correlates. We describe the predictive validity of four definitions of schizophrenia (DSM-III-R, ICD-10, ICD-9 and CATEGO S+), in a representative cohort of patients selected during their first episode of psychosis. METHOD: Each definition of schizophrenia was applied to 99 patients. Their respective ability to predict 13-year outcome (Global Assessment of Functioning scales) was assessed. RESULTS: DSM-III-R and ICD-10 diagnoses of schizophrenia have high predictive validity for long-term outcome, and both provide relatively stable diagnoses. ICD-9 is reasonably good at predicting disability, but not symptoms, and CATEGO S+ showed no predictive validity. Adding six-month duration criteria to ICD-10, ICD-9 and CATEGO S+ improved their predictive validity, and removing the six-month duration criterion from DSM-III-R commensurately reduced predictive validity. CONCLUSIONS: Modern diagnostic systems (DSM-III-R and ICD-10) have high predictive validity, and are superior to ICD-9. The six-month duration criterion of DSM-III-R schizophrenia accounts for its predictive validity and stability over 13 years, but restricts its use in first-episode studies. The one-month duration criterion of ICD-10 is less restrictive, without major compromises in predictive validity or stability.

The course of schizophrenia over 13 years. A report from the International Study on Schizophrenia (ISoS) coordinated by the World Health Organization.

BACKGROUND: This paper describes the 13 year course of illness in an epidemiologically defined and representative cohort of patients selected when they were experiencing their first episode of schizophrenia. METHOD: In a 13-year follow-up study of 67 patients with ICD-9 schizophrenia, identified in Nottingham in 1978-80, the course of illness (symptoms, disability and hospitalisation) was assessed using standardised instruments, applied at onset, 1,2, and 13 years. Time to first relapse and first readmission were calculated and plotted as survival curves and patients were assigned to the course types described by Ciompi. RESULTS: The survival curves show that first relapses and first readmissions occur during the first five years. The amount of time spent in psychotic episodes and in hospital is greatest in the first year of follow-up, but stable thereafter. Social adjustment improves from entry to the study to the first follow-up year, but there is a small deterioration in social adjustment between 2 and 13 years. CONCLUSIONS: The findings reported suggest that after the initial episode the course of schizophrenia is relatively stable. The data support neither concepts of progressive deterioration nor progressive amelioration. There was no evidence of a "late recovery'.

Predicting the long-term outcome of schizophrenia.

Predictors of long-term (13 year) outcome of schizophrenia are reported for a representative cohort of 'treated incidence' patients ascertained on their first contact with Nottingham psychiatric services between 1978-80. An initial (baseline) model including previously reported predictors of 2-year outcome (age, gender, ever married, acuteness of onset) and length of untreated illness was used to predict a range of outcome measures covering the domains of disability, psychopathology, hospitalization, employment, social activity, and global outcome. This model demonstrated significant prognostic ability across all non-hospitalization outcomes under both ICD-10 and ICD-9 diagnoses of schizophrenia, but was attenuated under broad (ICD-9 and CATEGO S, P or O) and restrictive (S+) diagnostic classifications. Female gender predicted more favourable outcome under all diagnostic classifications except S+. In an extended analysis, the addition of initial 2-year course type substantially increased the prognostic ability of the model under all diagnostic classifications and enabled over 30% of the variance in global ratings of disability and symptoms to be predicted. In this extended model female gender predicted more favourable outcome over and above the effect of course type, across most domains under ICD-10, and for disability and psychopathology under other diagnostic classifications. The inclusion of measures of psychopathology at the time of first assessment, pre-morbid functioning, and duration of index admission conferred only marginal additional predictive ability for respective outcomes in the domains of psychopathology, social activity, employment and hospitalization. Hospitalization during the past year was the most difficult outcome to predict under any model suggesting that resource utilization represents the 'administrative outcome' of schizophrenia and serves as a poor proxy for broader concerns in the era of community care. These data demonstrate that key demographic variables and the mode of onset influence the long-term course of schizophrenia, but that early course type is a particularly strong predictor.

Psychological consequences of the Kegworth air disaster.

BACKGROUND: The study sought to quantify psychiatric morbidity among survivors of a major air crash and to identify aetiological factors linked with post-traumatic stress disorder (PTSD). METHOD: Sixty-eight of the 79 survivors (86%) were assessed at a clinical interview within one year of the disaster. The majority also completed the General Health Questionnaire, the Impact of Events Scale (IES) and the Zung Anxiety and Depression Scales. RESULTS: Fifty-four of the study group (79%) met DSM-III-R criteria for a psychiatric disorder within one year of the disaster, of whom 27 (50%) had PTSD. Those who saw injured or dead people at the scene, or had sustained less severe injuries as measured by their Injury Severity Scores, or were under 35 years old, were significantly more likely to develop PTSD. CONCLUSIONS: High rates of psychiatric morbidity are found in survivors of transportation disasters. Further studies are needed to identify those at most risk and to evaluate the benefits of psychological intervention.

Characteristics of outcome in schizophrenia at 13 years.

BACKGROUND: This paper describes the 13-year outcome of an epidemiologically defined and representative cohort of patients selected when they were experiencing their first episode of schizophrenia. METHOD: In a 13-year follow-up study of a cohort identified in Nottingham in 1978-80, the outcome (symptoms, disability, residence and treatment) was assessed using standardised instruments. RESULTS: Four of the original 67 patients with ICD-9 schizophrenia were lost to follow-up and five were dead: 52% were without psychotic symptoms in the last two years of follow-up, 52% were without negative symptoms and 55% showed good/fair social functioning. However, only 17% were alive at follow-up, without symptoms and disability, and receiving no treatment. CONCLUSIONS: The findings reported are similar to those of other long-term follow-up studies of schizophrenia and also to 5-year follow-up studies. Kraepelin's emphasis on the longitudinal implications of a diagnosis of schizophrenia are supported, but may be over-pessimistic.

Residence of incident cohort of psychotic patients after 13 years of follow up.

OBJECTIVE: To establish the residential history of an incident cohort of psychotic patients 13 years after their first contact with the psychiatric services. DESIGN: Tracing of all patients admitted to the WHO study on determinants of outcome of severe mental disorders in Nottingham between 1978 and 1980. Patients were assessed using standardised and comparable instruments, and extra information was obtained from key informants and medical records. SETTING: Catchment area of Nottingham psychiatric services. MAIN OUTCOME MEASURES: Main place of residence over the previous two years and residential history over 13 years in terms of homelessness, imprisonment, and use of high dependency psychiatric facilities. RESULTS: 95 patients were traced. At the point of follow up no patients were in long stay psychiatric wards, two were in supervised residence, none was homeless, and none was in prison or a high security hospital. 85 patients were living either independently alone or with their family or friends in the community. Of these, 44 had had no contact with the psychiatric services at the point of follow up. CONCLUSIONS: Although many patients experienced a difficult early course of illness, the longer term outcome of the disorder was associated with remarkably low periods of homelessness and imprisonment and low use of intensive care facilities. These findings offer some reassurance, given the concerns about the effectiveness of community oriented care for this potentially most vulnerable group of psychiatric patients.

Premorbid personality in first-onset psychosis.

The data presented are those from a two-year prospective study of 69 patients identified in the Nottingham field centre of the WHO Study of Determinants of Outcome of Severe Mental Disorders. Premorbid personality, childhood adjustment and adolescent adjustment were assessed at the patients' first presentation to psychiatric services with a psychotic illness. Ratings were made blind to diagnosis. Premorbid explosive and paranoid traits were commoner in patients with schizophrenia than in patients with other non-organic psychoses, and these traits were associated with later onset of schizophrenia. Premorbid schizoid traits were significantly commoner in patients with schizophrenia compared to patients with other psychoses, but only in those patients for whom a parent was the informant. Schizoid traits were no commoner in men with schizophrenia than in women, and were not associated with earlier age of onset. The findings suggest that premorbid personality, in men and women, may shape the expression of symptoms produced during an illness episode.

An evaluation of structural and functional prefrontal deficits in schizophrenia: MRI and neuropsychological measures.

Magnetic resonance imaging was used to assess prefrontal brain structure in 17 schizophrenic, 18 psychiatric control, and 19 normal control subjects of comparable age, social background, and educational status, while three neuropsychological measures were used to assess prefrontal functioning. Schizophrenic patients had significantly smaller prefrontal areas than both psychiatric control and normal control subjects in all three planes. When posterior brain area and temporal lobe were entered into statistical analysis as covariates, they did not explain the prefrontal deficits. Schizophrenic patients made more perseveration errors on the Wisconsin Card Sorting Task and had fewer correct responses on the Spatial Delayed Response Task than normal control subjects. Schizophrenic patients performed more poorly than psychiatric control subjects on the Block Design Test. No group differences were found on three other nonfrontal tasks. These data lend some support to the role of prefrontal deficits in the development of schizophrenia.

Structural and functional characteristics of the corpus callosum in schizophrenics, psychiatric controls, and normal controls. A magnetic resonance imaging and neuropsychological evaluation.

In 1986 Nasrallah and colleagues found that increased thickness of the corpus callosum may be specific to right-handed female schizophrenics. Male and female right-handed schizophrenics were compared with normal and psychiatric controls of comparable age, sex, education, and social class on measures of callosal thickness from a midsagittal magnetic resonance imaging cut and neuropsychological tests of interhemispheric transfer. The sex difference in anterior and posterior callosal thickness in normal controls was reversed in schizophrenics, with the corpus callosum being thicker in female schizophrenics and thinner in male schizophrenics. Similar findings were also observed in the psychiatric control group. These structural differences were not paralleled by evidence of impaired interhemispheric transfer on neuropsychological tasks. These results support the finding of sex-dependent callosal abnormalities in schizophrenia but indicate that these abnormalities may not be specific to this illness.