Differential relationship between neurological and cognitive dysfunction in first episode psychosis patients and in healthy individuals.

The minor neurological and cognitive deficits consistently reported in psychoses may reflect the same underlying brain dysfunction. Still, even in healthy individuals minor neurological abnormalities are associated with worse cognitive function. Therefore, establishing which neurological and cognitive deficits are specific to psychosis is essential to inform the pathophysiology of this disorder. We evaluated a large epidemiological sample of patients with first episode psychosis (n=242) and a population-based sample of healthy individuals (n=155), as part of the AESOP study. We examined neurological soft signs using the Neurological Evaluation Scale (Buchanan and Heinrichs, 1989), and generalized and specific cognitive deficits (memory; verbal abilities; attention, concentration and mental speed; executive functions and working memory; language; visual constructual/perceptual abilities). In patients, more neurological signs across all subscales were associated with worse general cognitive function, while in controls this was only present for sensory integration and sequencing signs. Furthermore, in patients, but not in healthy individuals, more sensory integrative signs were associated with deficits in specific cognitive domains, such as memory, verbal abilities, language, visual/perceptual, executive function (p ranging <0.001-0.002); sequencing signs with language, executive function, and attention (p<0.001-0.004); and motor signs with poorer verbal abilities (p=0.001). These findings indicate the presence of specific associations between neurological and cognitive deficits in psychosis that are distinct from those of healthy individuals.

Translating the epidemiology of psychosis into public mental health: evidence, challenges and future prospects.

Genetic and environmental factors are associated with psychosis risk, but the latter present more tangible markers for prevention. We conducted a theoretical exercise to estimate the proportion of psychotic illnesses that could be prevented if we could identify and remove all factors that lead to increased incidence associated with ethnic minority status and urbanicity. Measures of impact by population density and ethnicity were estimated from incidence rate ratios [IRR] obtained from two methodologically-similar first episode psychosis studies in four UK centres. Multilevel Poisson regression was used to estimate IRR, controlling for confounders. Population attributable risk fractions [PAR] were estimated for our study population and the population of England. We considered three outcomes; all clinically relevant ICD-10 psychotic illnesses [F10-39], non-affective psychoses [F20-29] and affective psychoses [F30-39]. One thousand and twenty-nine subjects, aged 18-64, were identified over 2.4 million person-years. Up to 22% of all psychoses in England (46.9% within our study areas) could be prevented if exposures associated with increased incidence in ethnic minority populations could be removed; this is equivalent to 66.9% within ethnic minority groups themselves. For non-affective psychoses only, PAR for population density was large and significant (27.5%); joint PAR with ethnicity was 61.7%. Effect sizes for common socio-environmental risk indicators for psychosis are large; inequalities were marked. This analysis demonstrates potential importance in another light: we need to move beyond current epidemiological approaches to elucidate exact socio-environmental factors that underpin urbanicity and ethnic minority status as markers of increased risk by incorporating gene-environment interactions that adopt a multi disciplinary perspective.

The prevalence, diagnostic significance and demographic characteristics of Schneiderian first-rank symptoms in an epidemiological sample of first-episode psychoses.

BACKGROUND: The diagnostic significance of first-rank symptoms (FRSs) remains uncertain. Ethnic differences in FRSs may account for high rates of schizophrenia in minority groups. This study aims to examine the prevalence of FRSs in an epidemiological sample of first-episode psychoses stratified by relevant demographic variables. SAMPLING AND METHOD: We identified everyone aged 16-64 presenting with their first psychosis over 2 years in 3 UK centres. RESULTS: A total of 426 subjects had consensus diagnoses of DSM-IV and ICD-10 psychotic conditions. Thirty-eight percent (95% CI=33-42) reported FRSs; more frequent in those classified as having schizophrenia (DSM-IV: 55%, 95% CI=47-63; ICD-10: 51%, 95% CI=44-58) than those with affective psychoses (DSM-IV: 31%, 95% CI=22-39; ICD-10: 29%, 95% CI=21-38). FRSs in schizophrenia were more common in white British subjects, while in affective psychoses, they were more frequent in the black group. The sensitivities, specificities and positive predictive values for schizophrenia of FRSs were 55, 69 and 72% according to DSM-IV and 51, 71, 74% according to ICD-10, respectively. The sensitivities were higher in white British than in the black group. CONCLUSIONS: FRSs were common but unhelpful for differentiating schizophrenia from other psychoses as they occurred frequently in both diagnoses. Phenomenological differences did not explain the higher incidence of schizophrenia in black ethnic minority groups.

Neurological abnormalities and cognitive ability in first-episode psychosis.

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Neurological abnormalities and cognitive ability in first-episode psychosis.

BACKGROUND: It remains unclear if the excess of neurological soft signs, or of certain types of neurological soft signs, is common to all psychoses, and whether this excess is simply an epiphenomenon of the lower general cognitive ability present in psychosis. AIMS: To investigate whether an excess of neurological soft signs is independent of diagnosis (schizophrenia v. affective psychosis) and cognitive ability (IQ). METHOD: Evaluation of types of neurological soft signs in a prospective cohort of all individuals presenting with psychoses over 2 years (n=310), and in a control group from the general population (n=239). RESULTS: Primary (P<0.001), motor coordination (P<0.001), and motor sequencing (P<0.001) sign scores were significantly higher in people with any psychosis than in the control group. However, only primary and motor coordination scores remained higher when individuals with psychosis and controls were matched for premorbid and current IQ. CONCLUSIONS: Higher rates of primary and motor coordination signs are not associated with lower cognitive ability, and are specific to the presence of psychosis.

Self-harm in first-episode psychosis.

BACKGROUND: Little is known about self-harm occurring during the period of untreated first-episode psychosis. AIMS: To establish the prevalence, nature, motivation and risk factors for self-harm occurring during the untreated phase of first-episode psychosis. METHOD: As part of the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study, episodes of self-harm were identified among all incident cases of psychosis presenting to services in south-east London and Nottingham over a 2-year period. RESULTS: Of the 496 participants, 56 (11.3%) had engaged in self-harm between the onset of psychotic symptoms and first presentation to services. The independent correlates of self-harm were: male gender, belonging to social class I/II, depression and a prolonged period of untreated psychosis. Increased insight was also associated with risk of self-harm. CONCLUSIONS: Self-harm is common during the pre-treatment phase of first-episode psychosis. A unique set of fixed and malleable risk factors appear to operate in those with first-episode psychosis. Reducing treatment delay and modifying disease attitudes may be key targets for suicide prevention.

Duration of untreated psychosis and neuropsychological function in first episode psychosis.

PURPOSE: We investigated whether duration of untreated psychosis (DUP) prior to first presentation was associated with cognitive function in first episode psychosis (FEP) subjects. We predicted that longer DUP would be associated with greater neurocognitive impairment. METHOD: 180 subjects with schizophrenia (and 93 subjects with Other Psychoses) performed a neurocognitive battery assessing IQ, verbal learning, working memory, visual learning and speed of processing. DUP was defined as the number of days between first onset of psychotic symptoms and first contact with psychiatric services. RESULTS: Longer DUP was associated with impaired performance in verbal IQ (p=0.04), verbal learning (p=0.02), and verbal working memory (p=0.04) in FEP subjects with schizophrenia. These associations remained significant for verbal IQ when scores were corrected for age, gender, educational level and ethnicity. CONCLUSIONS: Longer DUP is associated with poorer neurocognitive ability in schizophrenia subjects at time of first presentation. Since this was a cross-sectional study we can not tell whether longer DUP was a cause or a consequence of the poorer performance.

Incidence of schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP Study.

BACKGROUND: The incidence of schizophrenia in the African-Caribbean population in England is reported to be raised. We sought to clarify whether (a) the rates of other psychotic disorders are increased, (b) whether psychosis is increased in other ethnic minority groups, and (c) whether particular age or gender groups are especially at risk. METHOD: We identified all people (n=568) aged 16-64 years presenting to secondary services with their first psychotic symptoms in three well-defined English areas (over a 2-year period in Southeast London and Nottingham and a 9-month period in Bristol). Standardized incidence rates and incidence rate ratios (IRR) for all major psychosis syndromes for all main ethnic groups were calculated. RESULTS: We found remarkably high IRRs for both schizophrenia and manic psychosis in both African-Caribbeans (schizophrenia 9.1, manic psychosis 8.0) and Black Africans (schizophrenia 5.8, manic psychosis 6.2) in men and women. IRRs in other ethnic minority groups were modestly increased as were rates for depressive psychosis and other psychoses in all minority groups. These raised rates were evident in all age groups in our study. CONCLUSIONS: Ethnic minority groups are at increased risk for all psychotic illnesses but African-Caribbeans and Black Africans appear to be at especially high risk for both schizophrenia and mania. These findings suggest that (a) either additional risk factors are operating in African-Caribbeans and Black Africans or that these factors are particularly prevalent in these groups, and that (b) such factors increase risk for schizophrenia and mania in these groups.

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study.

CONTEXT: Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE: To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN: Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING: Southeast London, Nottingham, and Bristol, England. PARTICIPANTS: One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES: The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis. RESULTS: All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS: There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes

CONTEXT Convention suggests uniformity of incidence of schizophrenia and other psychoses; variation would have implications for their causes and biological characteristics. OBJECTIVE To investigate variability in the incidence of psychotic syndromes in terms of place, ethnicity, age, and sex. DESIGN Three-center, prospective, comprehensive survey of clinically relevant first-onset psychotic syndromes over a 2-year period (1997-1999). Census data provided the denominator. SETTING Southeast London, Nottingham, and Bristol, England. PARTICIPANTS One million six hundred thousand person-years yielded 568 subjects aged 16 to 64 years with clinically relevant psychotic syndromes. MAIN OUTCOME MEASURES The World Health Organization Psychosis Screen and the Schedules for Clinical Assessment in Neuropsychiatry to classify, blind to ethnicity, all DSM-IV psychotic syndromes and the subclasses of schizophrenia, other nonaffective disorders, affective disorders, and substance-induced psychosis.

RESULTS All syndromes showed a characteristic age distribution. Schizophrenia was significantly more common in men (incidence rate ratio [IRR], 2.3 [95% confidence interval (CI), 1.7-3.1]); affective disorders occurred equally in men and women (IRR, 1.0 [95% CI, 0.7-1.3]). All psychoses were more common in the black and minority ethnic group (crude IRR, 3.6 [95% CI, 3.0-4.2]). Differences in age, sex, and study center accounted for approximately a quarter of this effect (adjusted IRR, 2.9 [95% CI, 2.4-3.5]) in each psychosis outcome. The age-sex standardized incidence rate for all psychoses was higher in Southeast London (IRR, 49.4 [95% CI, 43.6-55.3]) than Nottingham (IRR, 23.9 [95% CI, 20.6-27.2]) or Bristol (IRR, 20.4 [95% CI, 15.1-25.7]). Rates of all outcomes except affective disorders remained significantly higher in Southeast London when the model was expanded to control for ethnicity. CONCLUSIONS There is significant and independent variation of incidence of schizophrenia and other psychoses in terms of sex, age, ethnicity, and place. This confirms that environmental effects at the individual, and perhaps neighborhood level, may interact together and with genetic factors in the etiology of psychosis.

Determining the chronology and components of psychosis onset: The Nottingham Onset Schedule (NOS).

The Nottingham Onset Schedule (NOS) is a short, guided interview and rating schedule to measure onset in psychosis. Onset is defined as the time between the first reported/observed change in mental state/behaviour to the development of psychotic symptoms. Onset is conceptualised as comprising of (i) a prodrome of two parts: a period of 'unease' followed by 'non-diagnostic' symptoms; (ii) appearance of psychotic symptoms; and (iii) a build-up of diagnostic symptoms leading to a definite diagnosis. Twenty consecutive cases of first-episode psychosis were administered the NOS schedule to determine its psychometric properties including inter-rater and test-retest reliability. Its clinical and research potential as a reliable measure of duration of untreated psychosis (DUP) was assessed in a cohort of 99 cases of first-episode psychosis (56 schizophrenia, 43 affective psychoses). NOS identified all prodromal symptoms previously reported in other studies. There was high degree of inter-rater and test-retest reliability for all components of NOS. Duration of untreated psychosis was significantly longer (p<0.05) in schizophrenia (mean 179 days, S.D. 344; median 52 days) than in affective psychosis (mean 15 days, S.D. 116; median 12 days) but there were no gender differences between lengths of prodrome or treatment delays. The NOS provides a standardised and reliable way of recording early changes in psychosis and identifying relatively precise time points for measuring several durations in emerging psychosis. The scale is easy to use and is not time-consuming or labour intensive. Onset, as measured by NOS, is significantly longer in schizophrenic disorders than in affective psychosis. A small proportion of schizophrenia cases have very long DUP. Some cases with schizophrenia receive anti-psychotics in the prodromal phase, prior to the emergence of frank psychotic symptoms.

Incidence of bipolar affective disorder in three UK cities: results from the AESOP study.

BACKGROUND: There has been a relative dearth of epidemiological research into bipolar affective disorder. Furthermore, incidence studies of bipolar disorder have been predominantly retrospective and most only included hospital admission cases. AIMS: To determine the incidence of operationally defined bipolar disorder in three areas of the UK and to investigate any differences in gender and ethnicity. METHOD: All patients who contacted mental health services with first-episode psychosis or non-psychotic mania between September 1997 and August 1999 were identified and diagnosed according to ICD-10 criteria. Incidence rates of bipolar affective disorder were standardised for age and stratified by gender and ethnic group across the three areas. RESULTS: The incidence rate per 100,000 per year in south-east London was over twice that in Nottingham and Bristol. There was no significant difference in the rates of disorder in men and women. Incidence rates of bipolar disorder in the combined Black and minority ethnic groups in all three areas were significantly higher than those of the comparison White groups. CONCLUSIONS: The incidence of bipolar disorder was higher in south-east London than in the other two areas, and was higher among Black and minority ethnic groups than in the White population.

Minor physical anomalies in schizophrenia: is age a confounding factor?

Minor physical anomalies (MPAs) occur more frequently in a range of developmental disorders. They are also more frequent in schizophrenia supporting a neurodevelopmental aetiology of the illness. Contemporary MPA scales are yet to be validated for the effects of age. It is hypothesised that the effects of ageing may be confounding when these scales are applied to an elderly population. The distribution of MPAs in a normal elderly population was compared with younger subjects. Fifty subjects over the age of 60, and 50 subjects below the age of 60, with no known major mental illness, were evaluated. MPAs were assessed using a modified Lane scale [Psychol. Med. 27 (1997) 1155]. Elderly subjects showed an excess of absent trichions due to alopecia (p=0.004) short and broad palates (p=0.01) and greater ear protrusion (p=0.004) relative to young subjects. The differences reported are probably due to hair loss, edentulousness and growth of the auriculocephalic angle with age. These findings question the validity of studies of MPAs in schizophrenia that do not control for age.