Increased risk of psychosis in rural-born individuals: An Australian catchment-area study

The aim of the Brisbane Psychosis Study was to examine a range of candidate genetic and nongenetic risk factors in a large, representative sample of patients with psychosis and well controls. The patients (n=310) were drawn from a census conducted as part of the National Survey of Mental Health and Wellbeing. An age and sex-matched well control group (n = 303) was drawn from the same catchment area. Candidate risk factors assessed included migrant status of proband and proband's parents, occupation of father at time of proband's birth, place of birth and place of residence during the first 5 years of life (urbanicity), self-reported pregnancy and birth complications, season of birth and family history. The main analyses were group (cases versus controls) comparisons, with planned subgroup analyses (1) group comparisons for Australian-born subjects only, (2) within-patient comparisons of affective versus nonaffective psychoses. Of the individuals with psychosis, 68% had DSMIII-R schizophrenia. In the main analyses, there were no significant group differences on season of birth, place of birth, place of residency in the first 5 years, occupation of fathers at time of birth or pregnancy and birth complications. Patients had significantly more family members with schizophrenia. Significantly fewer of the patients were migrants or offspring of migrants compared to the controls. When only Australianborn subjects were assessed (n=457), the findings were essentially unchanged apart from a significant excess of cases born in rural sites (chi-square=9.54, df3, p=0.02). There were no significant differences in the risk factors for the comparison involving affective versus nonaffective psychoses. Potential explanations for the inverse urban-rural risk gradient are reviewed. The Stanley Foundation supported this project

Endorsement of CIDI psychosis screening items in the Australian Survey of Mental Health and Well being

This paper presents preliminary analysis of the endorsement of the CIDI Psychosis Screening items in a large Australian community sample. CIDI interviews were completed on a representative sample of 10,641 individuals living in private dwellings in Australia. The items examined constructs related to thought control/interference (G1), ideas of reference (G2), and special powers (G3). If endorsed, each item had a follow-up probe (G1A telepathy; G2A things arranged with special meaning; G3A -- group acceptability). The final item (G4) asked if the respondent had been told that they had schizophrenia. This paper presents the frequency of endorsement, and examines the impact of age and sex on these items. Endorsement of the items was G1 =5.86°/,,, G1A=0.70%, G2=4.84%, G2A=l.31%, G3=3.41%, G3A=2.65%, and G4=0.65%. If screen-positives are defined as two or more 'hits', then 0.41% of the sample met this criterion. Younger participants were significantly more likely to be screen-positive. Items G1, G1A, G2 and G2A were endorsed more frequently by younger participants while there were no significant age effects identified in items G3 or G4. There was a nonsignificant trend for females to endorse item G1 more frequently than males (p = 0.07), but there were no signficant gender differences on the other items. Many individuals who were 'screen-negative' for psychosis endorsed CIDI items related to thought controls, ideas of reference and special powers, suggesting that there may be a 'continuum' of experiences in the population. The impact of age on the distribution of these measures suggests either differential biological vulnerability to these experiences and/or differential cultural factors influencing endorsement of the items. The implications of these findings on our understanding of the symptoms of psychosis will be discussed. The survey was funded by the Commonwealth Dept. of Health and Family Services. The Stanley Foundation supported this project.

Gender and age-at-first-admission for schizophrenia: Data from Australia and Brazil

In order to examine whether different populations show the same pattern of onset in the Southern Hemisphere, we examined the age-at-first-admission distribution for schizophrenia based on mental health registers from Australia and Brazil. Data on age-at-first-admission for individuals with schizophrenia were extracted from two names-linked registers, (1) the Queensland Mental Health Statistics System, Australia (N=7651, F= 3293, M=4358), and (2) a psychiatric hospital register in Pelotas, Brazil (N=4428, F=2220, M=2208). Age distributions were derived for males and females for both datasets. The general population structure tbr both countries was also obtained. There were significantly more males in the Queensland dataset (gz = 56.9, df3, p < 0.0001 ). Both dataset distributions were skewed to the right. Onset rose steeply after puberty to reach a modal age group of 20-29 for men and women, with a more gradual tail toward the older age groups. In Queensland 68% of women with schizophrenia had their first admissions after age 30, while the proportion from Brazil was 58%. Compared to the Australian dataset, the Brazilian dataset had a slightly greater proportion of first admissions under the age 30 and a slightly smaller proportion over the age of 60 years. This reflects the underlying age distributions of the two populations. This study confirms the wide age range and gender differences in age-at-first-admission distributions for schizophrenia and identified a significant difference in the gender ratio between the two datasets. Given widely differing health services, cultural practices, ethic variability, and the different underlying population distributions, the age-at-first-admission in Queensland and Brazil showed more similarities than differences. Acknowledgments: The Stanley Foundation supported this project.

Age-at-first-admission of schizophrenia, bipolar disorder and major depression: Implications of heterogeneity

Age of onset is an important variable when considering the cause and course of mental illnesses. Given the debate about the relationship between psychotic disorders it would be useful to compare age-at-first-admission for ICD schizophrenia and for affective psychoses when the latter is differentiated into 'major depression' and 'bipolar disorder'. Data on age-at-first-admission for Australian-born individuals diagnosed with schizophrenia (ICD 295) or affective psychosis (ICD 296) were extracted from the Queensland Mental Health Statistics System -- a comprehensive, namelinked mental health register. Because the ICD 9 category 296.1 was used to code what is now called "major depressive episode', this group was differentiated from other 296 categorieswhich were considered bipolar disorders. Those receiving more than one diagnoses within these categories were excluded. All distributions show a wide age range of onset from early adolescence into the seventies and eighties. However the modal age-group for major depression ('60-69' for both sexes) is clearly different from bipolar disorder ('20-29' for males; '30- 39' for females), the latter distribution being more similar to the SCZ distribution (which had a model age-group of '20-29' for both sexes). While these distributions were similar for males and females, there were sex differences in the proportions within each diagnostic group: more males with schizophrenia, and more females with bipolar disorder and with major depression. Our results suggest heterogeneity within the affective psychoses as categorised by ICD 9, with bipolar disorder having an age-at-first-admission distribution more similar to schizophrenia than major depression. The Stanley Foundation supported this project.

Is there change over time in the season-of-birth effect for schizophrenia? Data from the southern hemisphere

The aim of this paper is to examine distributions of schizophrenia and general population births over time in order to determine whether (a) the pattern has changed over time, (b) any pattern was similar for both males and females, and (c) whether there is any indication that there is any relationship between the changes in pattern between schizophrenia and general population births. Birth month and year for 7807 individuals with ICD8/9 schizophrenia were gained from the Queensland Mental Health Statistical System for 1914-1975. Monthly births for the general population in Queensland for the same period were obtained from the Australian Bureau of Statistics. For each decade we obtained two comparisons, (1) between two 'seasons' (summer-autumn/winter-spring), and (2) between the third (coldest) quarter and the remaining quarters. Based on expected contrasts from general population proportions, odds ratios and their confidence intervals were used to analyse these comparisons for all subjects, and for males and females separately. The seasonality found in our previous studies was again evident (OR 1.09; 95% CI= 1.01-1.17). However there was no significant change in its pattern over time either for the total group or for males and females separately. When the general population births alone were examined using the same contrasts, seasonality was also observed, but here there were fluctuations over time. These results suggest that exposures linked to changes in general population births over time should be examined in disorders such as schizophrenia which demonstrate seasonality in births. The Stanley Foundation supported this project.

Between-year fluctuations in schizophrenia birth rate and associations with the Southern Oscillation Index, cloud cover and sunshine

Our group have recently proposed that low prenatal vitamin D may be a risk-modifying factor for schizophrenia. Climate variability impacts on vitamin D levels in a population via fluctuations in the amount of available UV radiation. In order to explore this hypothesis, we examined fluctuations in the birthrates for people with schizophrenia born between 1920 and 1967 and three sets of variables strongly associated with UV radiation. These included: (a) the Southern Oscillation Index (SOI), a marker of El Nino which is the most prominent meteorological factor that influences Queensland weather: (b) measures of cloud cover and (c) measures of sunshine. Schizophrenia births were extracted from the Queensland Mental Health register and corrected for background population birth rates. Schizophrenia birth rates had several apparently non-random features in common with the SO1. The prominent SO1 fluctuation event that occurred between 1937 and 1943 is congruent with the most prominent fluctuation in schizophrenia birth rates. The relatively flat profile of SOI activity between 1927 and 1936 also corresponds to the flattest period in the schizophrenia time series. Both time series have prominent oscillations in the 3 ~, year range between 1946 and 1960. Significant associations between schizophrenia birth rates and measures of both sunshine and cloud cover were identified,and all three time series shared periodicity in the 3-4 year range. The analyses suggest that the risk of schizophrenia is higher for those born during times of increased cloud cover,reduced sunshine and positive SO1. These ecological analyses provide initial support for the vitamin D hypothesis, however alternative non-genetic candidate exposures also need to be considered. Other sites with year-to-year fluctuations in cloud cover and sunshine should examine patterns of association between these climate variables and schizophrenia birth rates. The Stanley Foundation supported this project.

The continuum of quasi-psychotic beliefs and experiences in the Australian general public

When surveyed, many individuals without psychosis report a range of beliefs and experiences that are shared by patients with psychosis. This study aimed to examine quasi-psychotic beliefs and experiences in a sample of well Australians. 303 individuals were recruited from a defined catchment area as part of the Brisbane Psychosis Study. All subjects were screened with a modified SCAN in order to exclude psychoses. The Peters Delusional Inventory (PDI 40 items), items from the Chapmans' Psychosis Proneness Scale (PPS), the Communication Awareness Scale (CAS: a measure of awareness of thought disorder), items related to perceptions and beliefs from various schizotypy questionnaires and the Social Desirability (SD) items from the EPQ were administered. There was a significant negative correlation between age and total score on the PDI. There were significant positive correlations between the PDI, the PPS, the CAS and the items related to perception. There were no significant gender differences on any of the scores apart from SD (females had higher scores). Those with a positive family history of mental illness other than schizophrenia (n = 118) scored significantly higher on the PDI and scores related to perception, however they were no different on SD or the Psychosis Proneness items. There were no group differences on any of these items when those with a positive family history of schizophrenia (n = 27) were compared to the rest of the group. Well individuals who endorse delusional beliefs also tend to endorse items related to abnormal perceptions and awareness of thought disorder. The results of the study support the concept of a 'continuum of beliefs and experiences' in the general community that should inform our neurocognitive models of the symptoms of psychosis. The Stanley Foundation supported this project.

Dysmorphogenesis in psychosis: Quantitative and qualitative measures involving the head and face

In this study, we examined qualitative and quantitative measures involving the head and face in a sample of patients and well controls drawn from the Brisbane Psychosis Study. Patients with psychosis (n=310) and age and sex-matched controls (n=303) were drawn from a defined catchment area. Features assessed involved hair whorls (position, number, and direction), eyes (epicanthus), supraorbital ridge, ears (low set, protrusion, hypoplasia, ear lobe attachment, asymmetry, helix width), and mouth (palate height and shape, palate ridges, furrowed and bifid tongue). Quantitative measures related to skull size (circumference, width and length) selected facial heights and depths. The impact of selected risk factors (place and season of birth, fathers' occupation at time of birth, selfreported pregnancy and birth complications, family history) were examined in the entire group, while the association between age of onset and dysmorphology was assessed within the patient group. Significant group (cases versus controls) differences included: patients had smaller skull bases, smaller facial heights, larger facial depths, lower set and protruding ears, different palate shape and fewer palate ridges. In the entire sample significant associations included: (a) those with positive family history of mental illness bad smaller head circumference, cranial length and facial heights; (b) pregnancy and birth complications was associated with smaller facial beights: (c) larger head circumference was associated with higher ranked fathers' occupations at birth. Within the patient group, age of onset was significantly lower in those with more qualitative anomalies or with larger facial heights. The group differences were not due to outliers or distinct subgroups, suggesting that the factors responsible for the differences may be subtle and widely dispersed in the patient group. The Stanley Foundation supported this project.

The co-segregation of psychosis and selected physical disorders within families of patients with psychosis versus well controls

While it has been reported that individuals with psychosis are at increased or decreased risk of various physical disorders such as cancer and rheumatoid arthritis, there has been less research on the co-segregation of physical disorders within the first-degree relatives of those with psychosis compared to relatives of well controls. The aim of this study was to examine these issues in an epidemiologically informed catchment-area based case-control study. Patients with psychosis were drawn from a prevalence study undertaken as part of the Australian National Mental Health Survey. In addition, we recruited well controls who resided in the same catchment area. For each subject, we drew pedigrees and used a structured checklist to assess the presence of selected psychiatric disorders, and selected disorders such as multiple sclerosis, epilepsy, spina bifida, thyroid disorders, diabetes, asthma and eczema. Data based on pedigrees from 293 individuals with psychosis and 292 well controls was available. As expected, the odds of havingschizophrenia and affective disorders were significantly increased in the families of cases versus controls. The odds of havingeczema were significantly reduced in the relatives of those with psychosis. All other disorders occurred with equal frequency in cases versus control pedigrees. Current theories of eczema suggest that an absence of early life exposure to antigens and infectious agents may fail to prime the na¨ıve immune system, and leave the person at increased risk of eczema. The results of this study suggest that genetic andror environmental factors that facilitate psychosis may protect against eczema. The Stanley Foundation supported this project.

Decreased perinatal sunshine duration is associated with increased non-affective but not affective psychosis birth rates

We have previously found an association between variations in schizophrenia birth rates and varyinglevels of perinatal sunshine duration. This study examines whether such an association can also be found for Ža. affective psychosis, and Žb. broadly defined nonaffective psychoses. Data for individuals born between 1931 and 1970 in Australia with ICD9 Other PsychosisŽ295–299.were obtained from the Queensland Mental Health Statistical System. ‘Affective psychosis’ included affective psychosis, schizo-affective psychosis, and depressive and excitative non-organic psychoses. ‘Non-affective psychosis’ included chizophrenia, paranoid disorders and other non-organic psychoses. Those receiving both affective and non-affective psychotic diagnoses were excluded. Rates per 10,000 live monthly general population births were calculated. For each month, we assessed the agreementŽusing the kappa statistic. between trends in Ža. birth rates and Žb. long-term trends in seasonally adjusted perinatal sunshine duration. The analyses were performed separately for males and females. There were 6265 with non-affective psychosis ŽMs3964 rate 66r10,000; Fs2299 44r10,000. and 2858 with affective psychosisŽMs1392 24r10,000; Fs1466 28r10,000.. There were no significant associations between Ža. affective psychosis birth rates for either males or females and Žb. sunshine duration. There was a significant association between nonaffective psychosis birth rates for males only and Žb. sunshine duration Žkappas0.15 p-0.001.. This suggests that, as a risk factor, the effect of reduced perinatal sunshine is specifically associated with males who develop non-affective psychosis. The Stanley Foundation supported this project.

No association between the deficit syndrome in psychosis and summer birth in the Southern Hemisphere

Recent studies have shown that individuals with schizophrenia who are born in summer have an increased odds of have deficit syndrome versus nondeficit syndrome. This study extends this work to examiningthis issue in patients from the Southern Hemisphere. Data which included OPCRITrSCAN items and demographic information was obtained for Australian-born cases from the Australian National Mental Health Survey. Followingpreviously published methods, cases were assigned to the deficit group Žns153.or non-deficit groupŽns228.. A logistic regression analysis was used to ascertain whether beingborn in summer ŽDecember, January, February.in the Southern Hemisphere altered the odds of havingdeficit syndrome. There was no association between summer birth and odds of havingdeficit versus non-deficit schizophrenia ŽOdds Ratios0.75, 95% CI 0.49–1.16.. Based on our previous work showingthat the size of the winterrspringbirth excess in schizophrenia is reduced in the Southern Hemisphere, we speculate that factors that influence the association between summer birth and non-deficit syndrome may also vary across geography andror latitude. The Stanley Foundation supported this project.