Development and initial validation of a multivariable predictive Early Adversity Scale for Schizophrenia (EAS-Sz) using register data to quantify environmental risk for adult schizophrenia diagnosis after childhood exposure to adversity.

BACKGROUND: Additional to a child's genetic inheritance, environmental exposures are associated with schizophrenia. Many are broadly described as childhood adversity; modelling the combined impact of these is complex. We aimed to develop and validate a scale on childhood adversity, independent of genetic and other environmental liabilities, for use in schizophrenia risk analysis models, using data from cross-linked electronic health and social services registers. METHOD: A cohort of N = 428 970 Western Australian children born 1980-2001 was partitioned into three samples: scale development sample (N = 171 588), and two scale validation samples (each N = 128 691). Measures of adversity were defined before a child's 10th birthday from five domains: discontinuity in parenting, family functioning, family structure, area-level socioeconomic/demographic environment and family-level sociodemographic status. Using Cox proportional hazards modelling of follow-up time from 10th birthday to schizophrenia diagnosis or censorship, weighted combinations of measures were firstly developed into scales for each domain, then combined into a final global scale. Discrimination and calibration performance were validated using Harrell's C and graphical assessment respectively. RESULTS: A weighted combination of 42 measures of childhood adversity was derived from the development sample. Independent application to identical measures in validation samples produced Harrell's Concordance statistics of 0.656 and 0.624. Average predicted time to diagnosis curves corresponded with 95% CI limits of observed Kaplan-Meier curves in five prognostic categories. CONCLUSIONS: Our Early Adversity Scale for Schizophrenia (EAS-Sz), the first using routinely collected register data, predicts schizophrenia diagnosis above chance, and has potential to help untangle contributions of genetic and environmental liability to schizophrenia risk.

Hospital inpatient admissions of children of mothers with severe mental illness: A Western Australian cohort study.

BACKGROUND: Children of parents with mental illness face a number of adversities, potentially contributing to poor health. AIM: The aim of this study was to quantify the association between maternal severe mental illness and children's hospital admissions. METHOD: Record linkage cohort study of 467,945 children born in Western Australia between 1 January 1980 and 31 December 2001. Follow-up was from age 28 days until fifth birthday. Linked registers captured information on potential confounders. Rate ratios and adjusted rate ratios measured relative change in the numbers of admissions and total days of stay, while rate differences measured absolute change in outcomes. Cause-specific increases were calculated for ICD-9 chapters and for 'potentially preventable' conditions. RESULTS: After adjusting for potential confounders, children of mothers with severe mental illness had a 46% relative increased rate in hospital admissions (95% confidence interval = [38%, 54%]) and an absolute increase in 0.69 extra days in hospital per child, per year (95% confidence interval = [0.67, 0.70]). The relative increase in admissions was greatest in the child's first year of life (adjusted rate ratio = 1.76, 95% confidence interval = [1.64, 1.88]; rate difference = 0.32, 95% confidence interval = [0.30, 0.34]). Rates of admissions were increased for a range of causes, particularly injuries, infections and respiratory disease, and for conditions classified as 'potentially preventable'. CONCLUSION: Children of mothers with severe mental illness have a substantial excess in hospital use compared to children of well mothers. This vulnerable group should be targeted with interventions to avert preventable morbidity and premature mortality in later life.

Factors that contribute to urban-rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers.

INTRODUCTION: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. METHODS: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia (N = 428,784) and Denmark (N = 1,357,874). Children were categorised according to the level of urbanicity of their mother's residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. RESULTS: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). DISCUSSION: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.

Loneliness and its association with health service utilization in people with a psychotic disorder.

BACKGROUND: Loneliness is common in people with psychotic disorders and associated with reduced health and well-being. The relationship between loneliness in psychosis and health service use is unclear. This study examined whether loneliness predicts increased health care utilization in this population, independently of sociodemographics, health and functioning. METHODS: We used cross-sectional data from the Second Australian National Survey of Psychosis. Loneliness was assessed using a single-item question, rated on a 4-point scale (not lonely; lonely occasionally; some friends but lonely for company; socially isolated and lonely). Health service use (past 12-months) was measured by the number of general practitioner (GP), emergency department (ED) and outpatient visits, inpatient admissions, and home visits by mental health professionals. Frequent hospital users comprised those in the top 15% of users of at least two services. RESULTS: Negative binomial regression analysis showed that loneliness was associated with an increased number of GP visits, ED visits and inpatient admissions, only. Socially isolated and lonely survey participants were more than twice as likely (OR = 2.6) of being 'frequent users' compared to non-lonely responders. Following stringent adjustment for covariates, loneliness remained significantly associated with being a 'frequent user' and showed a non-significant trend to an increased number of GP visits and inpatient admissions. CONCLUSIONS: Loneliness is a complex social and personal problem for people with psychosis, related to greater use of some health services. Better strategies for identifying and responding to loneliness in this population have the potential to increase well-being and contain health service utilization costs.

Parsing components of risk of premature mortality in the children of mothers with severe mental illness.

INTRODUCTION: Children of mothers with severe mental illness are at increased risk of premature death including in infancy and early childhood. Importantly, these children are also more likely to be exposed to adverse socio-demographic risk factors and serious obstetric complications which, of themselves, may increase risk for childhood mortality. We examined mortality outcome at different ages up to 5 years taking account of these risks. METHOD: We used linked data across Western Australian whole-population psychiatric, inpatient, death, and midwives' registers to identify 15,486 births to mothers with severe mental illness and 452,459 births to mothers with no mental illness. Multivariable models were adjusted for exposure to adverse socio-demographic risk factors and serious obstetric complications. RESULTS: Overall risk of premature death was increased amongst children of mothers with severe mental illness (2.3%, 354 deaths) compared with children of mothers with no mental illness (1.4%, 6523 deaths); the same was true for specific risk of stillbirth, neonatal, post­neonatal and early childhood deaths. Risk was substantially attenuated after adjustment for adverse socio-demographic exposures, and further still after adjustment for exposure to serious obstetric complications. We observed no effects for the timing of maternal illness diagnosis. CONCLUSIONS: To minimise the risk of premature mortality in the children of mothers with severe mental illness, priority should be given to the prompt diagnosis of maternal mental illness with targeted delivery of high quality antenatal and psychiatric care, as well as social and structural supports for affected families that continue after birth.

Are familial liability for schizophrenia and obstetric complications independently associated with risk of psychotic illness, after adjusting for other environmental stressors in childhood?

OBJECTIVE: The interplay between genetic and environmental factors on risk for psychotic illness remains poorly understood. The aim of this study was to estimate independent and combined effects of familial liability for schizophrenia and exposure to obstetric complications on risk for developing psychotic illness, covarying with exposure to other environmental stressors. METHODS: This whole-population birth cohort study used record linkage across Western Australian statewide data collections (midwives, psychiatric, hospital admissions, child protection, mortality) to identify liveborn offspring (n = 1046) born 1980-1995 to mothers with schizophrenia, comparing them to offspring of mothers with no recorded psychiatric history (n = 298,370). RESULTS: Both maternal schizophrenia and pregnancy complications were each significantly associated with psychotic illness in offspring, with no interaction. Non-obstetric environmental stressors significantly associated with psychotic illness in offspring included the following: being Indigenous; having a mother who was not in a partnered relationship; episodes of disrupted parenting due to hospitalisation of mother, father or child; abuse in childhood; and living in areas of greatest socioeconomic disadvantage and with elevated rates of violent crime. Adjustment for these other environmental stressors reduced the hazard ratio for maternal schizophrenia substantially (from hazard ratio: 5.7, confidence interval: 4.5-7.2 to hazard ratio: 3.5, confidence interval: 2.8-4.4), but not the estimate for pregnancy complications (hazard ratio: 1.1, confidence interval: 1.0-1.2). The population attributable fraction for maternal schizophrenia was 1.4 and for pregnancy complications was 2.1. CONCLUSION: Our finding of a substantial decrease in risk of psychotic illness associated with familial liability for psychosis following adjustment for other environmental stressors highlights potentially modifiable risk factors on the trajectory to psychotic illness and suggests that interventions that reduce or manage exposure to these risks may be protective, despite a genetic liability.

Sex differences in the cardiometabolic health of cannabis users with a psychotic illness.

BACKGROUND: Growing evidence shows cannabis use is associated with lower rates of metabolic dysregulation. Despite cannabis impacting each sex differently, few studies have examined the metabolic profile of male and female cannabis users separately. Our aim was to investigate sex differences in the impact of cannabis use on metabolic syndrome in adults with psychotic illness. METHOD: Data from 1078 men and 735 women interviewed in the second Australian national survey of psychosis were analyzed using multiple logistic regression to model separately, for each sex, the influence of no, occasional and frequent past-year cannabis use on metabolic syndrome, adjusting for potential covariates including antipsychotic medication, smoking, and physical activity. RESULTS: The proportion of women and men with metabolic syndrome was 58.1% and 57.6% respectively. Unadjusted analyses showed frequent cannabis use was associated with significantly lower odds of metabolic syndrome for both sexes. In adjusted analyses, the association between metabolic syndrome and frequent cannabis use remained significant for men (AOR = 0.49, 95% CI = 0.31-0.78), but not for women (AOR = 0.68, 95% CI = 0.37-1.24). Frequent cannabis use was associated with lower odds of abdominal obesity, hypertension and elevated triglyceride levels in men only. CONCLUSIONS: The differences we found suggest cannabinoid regulation of energy balance may be sex-dependent and highlight the importance of examining cannabis use in men and women separately. At the same time, the negative association between cannabis and psychosis onset and relapse should not be dismissed.

Intellectual Disability and Psychotic Disorders in Children: Association With Maternal Severe Mental Illness and Exposure to Obstetric Complications in a Whole-Population Cohort.

OBJECTIVE: Children of mothers with severe mental illness are at significantly increased risk of developing intellectual disability. Obstetric complications are also implicated in the risk for intellectual disability. Moreover, children of mothers with severe mental illness are more likely to be exposed to obstetric complications. The purpose of this study was to examine the independent and joint contributions of familial severe mental illness and obstetric complications to the risk of intellectual disability. METHOD: Record linkage across Western Australian whole-population psychiatric, inpatient, birth, and midwives' registers identified 15,351 children born between 1980 and 2001 to mothers with severe mental illness and 449,229 children born to mothers with no mental illness. Multivariable models were adjusted for paternal psychiatric status, parental intellectual disability, and other family and sociodemographic covariates. RESULTS: The risk of intellectual disability was increased among children of mothers with severe mental illness compared with children of unaffected mothers. The impact varied across maternal diagnostic groups. For children of mothers with schizophrenia, the unadjusted odds ratio was 3.8 (95% CI=3.0, 4.9) and remained significant after simultaneous adjustment for exposure to obstetric complications and other covariates (odds ratio=1.7, 95% CI=1.3, 2.3). The odds ratio for exposure to obstetric complications also remained significant after adjustment (odds ratio=1.7, 95% CI=1.6, 1.8). For intellectual disability of a genetic basis, the adjusted odds ratio for maternal schizophrenia was elevated but not statistically significant. Among children with intellectual disability, 4.2% later developed a psychotic disorder, compared with 1.1% of children without intellectual disability. CONCLUSIONS: Maternal severe mental illness and exposure to obstetric complications contribute separately to the risk of intellectual disability, suggesting potentially different causal pathways.

The impact of current cannabis use on general cognitive function in people with psychotic illness.

BACKGROUND: Despite growing research, it remains unclear if cannabis use is associated with additive cognitive impairment in people with psychotic illness and whether exposure in early adolescence is associated with poorer cognitive performance in adulthood. METHODS: This cross-sectional study of a nationally representative sample of 1199 adults with psychotic illness compared current cognition (digit symbol coding) of 297 current users of cannabis (used in the past year), 460 past users (used previously but not in the past year) and 442 non-users (never used). Multiple logistic regression was used to examine whether cognitive performance of cannabis-user groups varied by exposure age and diagnosis (non-affective/affective psychoses). RESULTS: Unadjusted analysis showed current cannabis users had significantly higher odds of impaired cognitive function compared to non-users (odds ratio=1.52, 95%CI=1.04-2.22). After adjusting for potential confounders, differences between the three groups were not significant. Exposure age was not significant in adjusted analysis. In participants with nonaffective psychoses, cognitive ability of current cannabis users did not differ from non-users. However, in participants with affective psychoses, using cannabis in the last year was a significant predictor of impaired cognitive function (odds ratio=2.25, 95%CI=1.05-4.84). CONCLUSION: Among people with psychotic illness, there was no significant difference in cognitive function between current, past and non-users of cannabis. However, when we compared cognitive performance of the three cannabis groups by diagnostic grouping, current cannabis use had a significant negative relationship with cognitive function in people with affective psychoses, but not in those with non-affective psychoses. This finding requires replication and further investigation.

Academic Performance in Children of Mothers With Schizophrenia and Other Severe Mental Illness, and Risk for Subsequent Development of Psychosis: A Population-Based Study.

OBJECTIVE: We examined the academic performance at age 12 years of children of mothers diagnosed with schizophrenia or other severe mental illness using a large whole-population birth cohort born in Western Australia. We investigated the association between academic performance and the subsequent development of psychotic illness. METHOD: The sample comprised 3169 children of mothers with severe mental illness (schizophrenia, bipolar disorder, unipolar major depression, delusional disorder or other psychoses; ICD-9 codes 295-298), and 88 353 children of comparison mothers without known psychiatric morbidity. Academic performance of children was indexed on a mandatory state-wide test of reading, spelling, writing and numeracy. RESULTS: A larger proportion of children (43.1%) of mothers with severe mental illness performed below the acceptable standard than the reference group (30.3%; children of mothers with no known severe mental illness). After adjusting for covariates, children of mothers with any severe mental illness were more likely than the reference group to perform below-benchmark on all domains except reading. For all children, poor spelling was associated with the later development of psychosis, but particularly for those at familial risk for severe mental illness (hazard ratio [HR] = 1.81; 95% CI for HR = 1.21, 2.72). CONCLUSIONS: Children of mothers with a severe mental illness are at increased risk for sub-standard academic achievement at age 12 years, placing these children at disadvantage for the transition to secondary school. For children with familial risk for severe mental illness, very poor spelling skills at age 12 years may be an indicator of risk for later psychotic disorder.

Medication for psychosis--consumption and consequences: the second Australian national survey of psychosis.

BACKGROUND: Most people diagnosed with a psychotic disorder will be prescribed psychotropic medication. The second Australian national survey of psychosis provided a unique opportunity to examine the pharmacological treatment of psychotic disorders from the perspective of the consumer. The aim of this paper is to report on medication use, adherence and perceived efficacy, and to describe side effect profiles. METHOD: Data on self-reported medication use in the 4 weeks prior to interview, including type, duration, adherence, side effects and helpfulness was collected from participants interviewed in the course of the second Australian national survey of psychosis. RESULTS: The majority (91.6%) of participants were using psychotropic medication: 89.0% of people aged 18-34 years and 93.5% of people aged 35-64 years. The most commonly used class of medication was antipsychotic medication (81.6%). In addition, 37.4% were using antidepressants, 26.7% were using mood stabilisers and 17.8% were using anxiolytics/hypnotics. Polypharmacy was common with almost two-thirds (63.4%) using more than one class of medication and over a quarter (28.1%) of people with schizophrenia using more than one antipsychotic. Many participants (84.4%) reported experiencing side effects. The side effect profile of people using atypical antipsychotics was on average better than that of people using typical antipsychotics. Most people (85.2%) felt their medication relieved their mental health symptoms and most (88.2%) medication was taken as prescribed. CONCLUSIONS: Many people with a psychotic disorder are receiving antipsychotics, with a substantial proportion also taking antidepressants, mood stabilisers and anxiolytics/hypnotics. Medication use differs by age group, diagnostic group and course of illness. Many people using antipsychotics describe significant impairment in their everyday life as a result of medication side effects. Users of typical antipsychotics reported more side effects and more impairment than people using atypical antipsychotics. Most of our participants were prescribed psychotropic medications, and most reported that they were taking them.