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Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in patients and relatives, and sought to establish whether antisaccade measures could differentiate between two patients clusters identified in the Western Australian Family Study of Schizophrenia with either pervasive cognitive deficits (CD) or cognitively spared (CS). Ninety-three patients (CD = 47, CS = 46), 99 relatives and 62 healthy controls carried out a standard antisaccade task. Results showed: (i) significantly greater error rate, and prolonged latencies to correct responses and self-correction saccades in patients compared with controls; (ii) high error rates in relatives of poorly performing patients; (iii) longer latencies of self-correction saccades in relatives compared to controls; and (iv) higher error rate and longer latencies of self-correction saccades in the CD subgroup compared with CS. Unaffected relatives as a group were unimpaired in error rate as compared to healthy controls. These findings suggest that the antisaccade error rate and latency of self-correction saccades are useful measures in specific applications of genetic research in schizophrenia, without fully meeting endophenotype co-familiality requirements. (Contains 4 tables and 3 figures.)

Objectives: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. Methods: We performed a case–control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. Results: The strongest finding (p = 2.01 × 10−6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance (p = 2.78 × 10−6). Conclusion: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Phenotypic heterogeneity is a major barrier to understanding the genetic architecture underlying schizophrenia. Incorporating endophenotypes is one way to reduce heterogeneity and facilitate more powerful genetic analysis. Candidate endophenotypes require systematic assessment against endophenotype criteria, and a ranking of their potential utility for genetic analysis. In this study we assess 20 cognitive and personality measures in a sample of 127 families with at least 2 cases of schizophrenia per family (n = 535) plus a set of 30 control families (n = 121) against 4 endophenotype criteria: (a) be associated with the illness but not be a part of its diagnosis, (b) be heritable, (c) co-segregate with the illness in families, and (d) be found in unaffected relatives at a higher rate than in the general population. The endophenotype ranking score (endophenotype ranking variable [ERV]) was used to rank candidate endophenotypes based on their heritability and genetic correlation with schizophrenia. Finally, we used factor analysis to explore latent factors underlying the cognitive and personality measures. Evidence for personality measures as endophenotypes was at least equivalent to that of the cognitive measures. Factor analysis indicated that personality and cognitive traits contribute to independent latent dimensions. The results suggest for this first time that a number of cognitive and personality measures are independent and informative endophenotypes. Use of these endophenotypes in genetic studies will likely improve power and facilitate novel aetiological insights. [ABSTRACT FROM AUTHOR]

Introduction: The Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines for the management of schizophrenia and related disorders provide evidence-based recommendations for optimising treatment and prognosis. This update to the 2005 RANZCP guidelines has a greater emphasis on psychosocial treatments, physical health comorbidities and vocational rehabilitation. Main recommendations: The guidelines advise a clinical staging approach and deliver specific recommendations for:•comprehensive treatment using second generation antipsychotic agents continuously for 2-5 years;•early treatment of comorbid substance use;•community treatment after initial contact, during crises and after discharge from hospital;•physical health monitoring and management of comorbidities, particularly metabolic health;•interventions to optimise recovery of social function and return to study or work; and•management of schizophrenia in specific populations and circumstances. Changes in management as a result of the guidelines: The guidelines provide benchmarks against which the performance of services and clinical teams can be assessed. Measuring treatment response and clinical outcome is essential. General practitioners have an important role, particularly in monitoring and reducing the high cardiovascular risk in this population. Clinical services focusing on early detection, treatment and recovery need continuous funding to be proactive in implementing the guidelines and closing the gap between what is possible and what actually occurs. [ABSTRACT FROM AUTHOR]

Objective: The objective is to summarise recent findings from the 2010 Australian Survey of High Impact Psychosis (SHIP) and examine their implications for future policy and planning to improve mental health, physical health and other circumstances of people with a psychotic disorder. Methods: Survey of High Impact Psychosis collected nationally representative data on 1825 people with psychotic illness. Over 60 papers have been published covering key challenges reported by participants: financial problems, loneliness and social isolation, unemployment, poor physical health, uncontrolled symptoms of mental illness, and lack of stable, suitable housing. Findings are summarised under the rubric of participant-ranked top challenges. Results: The main income source for the majority (85%) of participants was a government benefit. Only one-third was employed, and the most appropriate employment services for this group were under-utilised. High rates of loneliness and social isolation impacted mental and physical health. The rate of cardiometabolic disease was well above the general population rate, and associated risk factors were present from a very young age. Childhood abuse (30.6%), adult violent victimisation (16.4%) and alcohol and substance abuse/dependence (lifetime rates of 50.5% and 54.5%, respectively) complicated the clinical profile. Treatment with medication was suboptimal, with physical health conditions undertreated, a high rate of psychotropic polypharmacy and underutilisation of clozapine in chronic persistent psychotic illness. Only 38.6% received evidence-based psychosocial therapies. In the previous year, 27.4% had changed housing and 12.8% had been homeless, on average for 155 days. Conclusion: Money, social engagement and employment are the most important challenges for people with psychotic illness, as well as good physical and mental health. An integrated approach to recovery is needed to optimise service delivery and augment evidence-based clinical practice with measures to improve physical health and social circumstances. Meeting these challenges has the potential to reduce costs to government and society, as well as promote recovery. [ABSTRACT FROM AUTHOR]

Objectives: This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encourage all clinicians to adopt best practice principles. The recommendations represent the consensus of a group of Australian and New Zealand experts in the management of schizophrenia and related disorders. This guideline includes the management of ultra-high risk syndromes, first-episode psychoses and prolonged psychoses, including psychoses associated with substance use. It takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function. Methods: The writing group planned the scope and individual members drafted sections according to their area of interest and expertise, with reference to existing systematic reviews and informal literature reviews undertaken for this guideline. In addition, experts in specific areas contributed to the relevant sections. All members of the writing group reviewed the entire document. The writing group also considered relevant international clinical practice guidelines. Evidence-based recommendations were formulated when the writing group judged that there was sufficient evidence on a topic. Where evidence was weak or lacking, consensus-based recommendations were formulated. Consensus-based recommendations are based on the consensus of a group of experts in the field and are informed by their agreement as a group, according to their collective clinical and research knowledge and experience. Key considerations were selected and reviewed by the writing group. To encourage wide community participation, the Royal Australian and New Zealand College of Psychiatrists invited review by its committees and members, an expert advisory committee and key stakeholders including professional bodies and special interest groups. Results: The clinical practice guideline for the management of schizophrenia and related disorders reflects an increasing emphasis on early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes. The guideline uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care. This guideline also refers its readers to selected published guidelines or statements directly relevant to Australian and New Zealand practice. Conclusions: This clinical practice guideline for the management of schizophrenia and related disorders aims to improve care for people with these disorders living in Australia and New Zealand. It advocates a respectful, collaborative approach; optimal evidence-based treatment; and consideration of the specific needs of those in adverse circumstances or facing additional challenges. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to establish the 12-month prevalence of violent victimisation in a large sample of adults with psychotic disorders (N = 1825), compare this to population estimates, and examine correlates of violent victimisation.Methods: The Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders. Interview questions included psychopathology, cognition, sociodemographics, substance use, criminality, and childhood and adult victimisation. Multivariable logistic regression models were used to examine the independent contributions of known risk factors, clinical profile and childhood abuse, on risk of violent victimisation. Differences between men and women were examined.Results: Among adults with psychotic disorders, 12-month prevalence of any victimisation was 38.6% (males 37.4%, females 40.5%), and of violent victimisation was 16.4% (males 15.2%; females 18.3%). Violent victimisation was 4.8 times higher than the population rate of 3.4% (6.5 times higher for women; 3.7 times higher for men). Significant correlates of violent victimisation were established sociodemographic and behavioural risk factors predicting victimisation in the general community: younger age, residence in the most disadvantaged neighbourhoods, homelessness, lifetime alcohol abuse/dependence, and prior criminal offending. Among clinical variables, only mania and self-harm remained significant in the multivariable model. Childhood abuse was independently associated with violent victimisation.Conclusions: Rates of violent victimisation are high for people with psychotic disorders, especially women, compared to population rates. Greater exposure to sociodemographic and behavioural risks may render them particularly vulnerable to victimisation. Social cognition as a valuable treatment target is discussed. [ABSTRACT FROM AUTHOR]

BackgroundThere are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.MethodThe 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.ResultsThe 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.ConclusionsOur findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness. [ABSTRACT FROM PUBLISHER]

We investigated the existence of a temporal association between age at initiation of cannabis use and age at onset of psychotic illness in 997 participants from the 2010 Survey of High Impact Psychosis (SHIP) in Australia. We tested for group differences in age at onset of psychotic illness and in the duration of premorbid exposure to cannabis (DPEC). Analyses were repeated in subgroups of participants with a schizophrenia-spectrum disorder (SSD), a diagnosis of lifetime cannabis dependence (LCD), and a comorbid SSD/LCD diagnosis. The association between age at initiation of cannabis use and age at onset of psychotic illness was linear and significant, F(11, 984) = 13.77, P < .001, even after adjusting for confounders. The effect of age at initiation of cannabis use on DPEC was not significant (mean duration of 7.8 years), and this effect was similar in participants with a SSD, LCD, and comorbid SSD/ LCD diagnosis although a shift toward shorter premorbid exposure to cannabis was noted in the SSD/LCD subgroup (mean duration of 7.19 years for SSD/LCD). A temporal direct relationship between age at initiation of cannabis use and age at onset of psychotic illness was detected with a premorbid exposure to cannabis trend of 7–8 years, modifiable by higher severity of premorbid cannabis use and a diagnosis of SSD. Cannabis may exert a cumulative toxic effect on individuals on the pathway to developing psychosis, the manifestation of which is delayed for approximately 7–8 years, regardless of age at which cannabis use was initiated. [ABSTRACT FROM PUBLISHER]

The article reports a study which was conducted to test the hypothesis that consumption of amphetamine and/or cocaine in addition to cannabis would lead to an earlier age at onset of schizophrenia than that seen for cannabis consumption alone. The results confirmed the hypothesis. These findings suggest that additional consumption of each substance predicted an earlier age at onset by approximately 1 additional year.

The article describes recent trends in the use of medications in the management of psychotic disorders and explores adherence, side effects and treatment efficacy from the participant's perspective based on the second Australian national survey of psychosis. The survey revealed that the majority of participants were using antipsychotic medication and a considerable number of people were taking antidepressants, mood stabilizers and anxiolytics/hypnotics.

The article discusses the finding from the Survey of High Impact Psychosis (SHIP) 2010, the second such survey from Australia, and provides an overview of comparisons with the first psychosis survey. The finding from the survey suggested that people with psychotic illness face multiple challenges. Comparisons with data from the 1997−98 survey indicate that things have improved for these people but there are still major areas of concern.

Objective: This article describes the establishment of the Australian Schizophrenia Research Bank (ASRB), which operates to collect, store and distribute linked clinical, cognitive, neuroimaging and genetic data from a large sample of people with schizophrenia and healthy controls. Method: Recruitment sources for the schizophrenia sample include a multi-media national advertising campaign, inpatient and community treatment services and non-government support agencies. Healthy controls have been recruited primarily through multi-media advertisements. All participants undergo an extensive diagnostic and family history assessment, neuropsychological evaluation, and blood sample donation for genetic studies. Selected individuals also complete structural MRI scans. Results: Preliminary analyses of 493 schizophrenia cases and 293 healthy controls are reported. Mean age was 39.54 years (SD = 11.1) for the schizophrenia participants and 37.38 years (SD = 13.12) for healthy controls. Compared to the controls, features of the schizophrenia sample included a higher proportion of males (cases 65.9%; controls 46.8%), fewer living in married or de facto relationships (cases 16.1%; controls 53.6%) and fewer years of education (cases 13.05, SD = 2.84; controls 15.14, SD = 3.13), as well as lower current IQ (cases 102.68, SD = 15.51; controls 118.28, SD = 10.18). These and other sample characteristics are compared to those reported in another large Australian sample (i.e. the Low Prevalence Disorders Study), revealing some differences that reflect the different sampling methods of these two studies. Conclusion: The ASRB is a valuable and accessible schizophrenia research facility for use by approved scientific investigators. As recruitment continues, the approach to sampling for both cases and controls will need to be modified to ensure that the ASRB samples are as broadly representative as possible of all cases of schizophrenia and healthy controls. [ABSTRACT FROM AUTHOR]

The relationship of iron status with cognition and dementia risk in older people is contentious. We have examined the longitudinal relationship between serum ferritin and cognition in 800 community-dwelling Australians 60 years or older. Iron studies (serum iron, transferrin saturation, serum ferritin) were performed in 1994/5 and 2003/4 and clinical and cognitive assessments were conducted in 2003/4 for 800 participants of the Busselton Health Study. All participants completed the Cambridge Cognitive test (CAMCOG). Those with CAMCOG scores <84 underwent expert clinical review for cognitive disorders, including the Clinical Dementia Rating scale. Mean serum iron (18.3 μmol/l) and transferrin saturation (28.5%) in 2003/4 did not differ significantly from 1994/5 whereas mean serum ferritin decreased from 162 μg/l in 1994/5 to 123 μg/l in 2003/4, possibly reflecting aging or dietary changes. No relationships were observed between serum iron or transferrin saturation and presence or absence of dementia (p> 0.05). In participants without dementia (n=749), neither serum ferritin in 1994/5 or 2003/4 nor change in serum ferritin between these times was related to total CAMCOG or executive function scores, with or without adjustment for gender, age, National Adult reading test, or stroke history (all p> 0.05). No relationships were observed between ferritin and cognition for participants with possible or probable dementia (n=51). All participants identified as HFE C282Y homozygous or with serum ferritin >1,000 ng/ml had normal CAMCOG scores. We conclude abnormal body iron stores (low or high) are unlikely to have clinically significant effects on cognition or dementia risk in community-dwelling older people. [ABSTRACT FROM AUTHOR]

The article presents a research related to the impact of schizophrenia on social organization and urbanicity in Australia. It states that schizophrenia is the most common of the psychotic disorders and is characterized by fundamental distortions of thought, perception and emotional response. The aim of the study was to identify the influence or area residence on arrest and on recorded diagnoses of schizophrenia. Furthermore, the study takes advantage of prior record linkage between two population-based registers, the Western Australian Mental Health Information System and the Western Australian Arrestee Database.

Objective: To examine how women differ from men in their expression and experience of psychosis. Method: Using an epidemiological sampling frame, 1090 cases of psychosis (schizophrenia, schizoaffective disorder, affective psychoses, and other psychoses) were randomly selected from a catchment of 1.1million people as part of the Australian Study of Low Prevalence (Psychotic) Disorders. Women and men were compared with respect to their premorbid functioning, onset and course of illness, symptomatology, levels of disability and service utilization. Results: Results within diagnostic groupings confirm differences in how men and women experience and express their illness. Within each diagnostic group, women reported better premorbid functioning, a more benign illness course, lower levels of disability and better integration into the community than men. They were also less likely to have a chronic course of illness. There were no significant differences in age at onset. Differences between women across the diagnostic groups were more pronounced than differences between women and men within a diagnostic group. In particular, women with schizophrenia were severely disabled compared to other women. Conclusions: These comparisons across diagnostic groupings are among the most systematic and comprehensive in the literature. It is likely that several mechanisms are needed to explain the differences. Greater social integration and functioning in women across diagnostic groups may well reflect culturally and socially determined gender differences. In contrast, variability and attenuated findings with respect to symptom profiles beg the question of biological mechanisms with some degree of specificity. [ABSTRACT FROM AUTHOR]

This study examined variables associated with having aonce-only contactwith the out-patient department of two community mental health services in Italy and Australia.Two 8-year cohorts of patients, who had a new episode of care with out-patient psychiatric departments in South Verona and in Western Australia, were followed-up for 3 months after the first contact, to identify those patients who had no further contact with services. Potential determinants ofonce-only contactwere analysed.Thirty percent of new episodes of care for persons who met the inclusion criteria of the study wereonce-only contactswith the service in South Verona. In Western Australia, the figure was 24%. Moreover, the proportion ofonce-only contactpatients has increased over time in South Verona whereas, in Western Australia, it has remained stable. In Western Australia,once-only contactpatients were younger whereas in South Verona they tended to be older. At both research sites, patients who had aonce-only contactwere more likely to be male and to have a less severe mental illness.The results of this study suggest that only clinical characteristics were significant determinants of this pattern of contact with services consistently at both sites: the less severe the patient's diagnosis, the more likely the patient is to have aonce-only contact. This may well indicate good screening at the initial point of contact by both sets of mental health service providers. Prospective studies are necessary to clarify the problem of‘once-only contact’ and to organize a proper psychiatric care. [ABSTRACT FROM AUTHOR]

Objective: To describe patterns of self-reported medication use in a population-based sample of people with psychotic disorders; to establish correlates with clinical variables; to determine perceived side-effect burden; and investigate patient perception of efficacy for different classes of antipsychotic agent. Methods: Using the Australian Low Prevalence (Psychosis) Study database we analysed patterns of psychotropic medication and examined their clinical correlates. We also determined rates of reported side-effects and perceived benefit or otherwise associated with the different antipsychotic drugs. Results: Of the 1126 persons interviewed, 88.6% were on psychotropic medication; 54.3% were using ‘typical’ antipsychotics (24.8% in depot form), while 8.3% were on clozapine, 13.3% on risperidone, and 8.8% on olanzapine. Around 30% of women, and 20% of men, were on mood stabilizers or antidepressants. Over half of respondents were on more than one agent. Of those on only one agent, nearly 80% reported at least one side-effect; the mean number of side-effects was 3.9 for typical antipsychotics, and 3.3 for atypicals. Atypicals, notably clozapine, tended to be rated by patients as more efficacious than typicals; depot preparations, in particular, tended to be seen as unhelpful, and were associated with a higher side-effect burden. Conclusions: This study presents an insight into patients’ perception of efficacy and side-effects of antipsychotic medications. The findings have implications for clinicians, and can inform treatment options in people with psychotic disorders. [ABSTRACT FROM AUTHOR]

Objective: We aimed to use data from the Australian Survey of Mental Health and Well-being to examine the psychometric properties of the Diagnostic Interview for Psychosis-Disability Module (DIP-DIS). The DIP-DIS is a semi-structured questionnaire specially designed to assess disability associated with psychotic disorders. Method: The psychometric properties of the instrument were determined by examining its inter-rater reliability, internal structure, as well as its criterion and discriminant validities. Results: Analysis shows: (1) that it can be rated reliably by trained interviewers, (2) that the items are complementary but tap a number of different domains, (3) that four factors account for over 66% of the variance, and (4) that it is sensitive to differing clinical populations with expected differences in level of disability. Ratings on the DIP-DIS bore significant relationships with a criterion measure of quality of life. Conclusions: The DIP-DIS has encouraging psychometric properties for cross-sectional assessment of disability and may be useful in future studies of disablement associated with psychosis. Future work should examine its sensitivity to change. [ABSTRACT FROM AUTHOR]

Objective: This study examines seasonality birth effects in schizophrenia and affective psychoses in the southern hemisphere, given possible confounding of age incidence effects with winter birth peaks in northern hemisphere data. Method: Distributions of births by season, quarter and month for individuals born in Western Australia 1916-61 with a diagnosis of schizophrenia (N = 2284), affective psychoses (N = 3236), and neurotic depression (N = 4869) on the statewide mental health register were compared with distributions for the general population. Results: We found no association between season of birth and schizophrenia, affective psychoses or neurotic depression. For schizophrenia, the pattern of risks by quarter reflects northern hemisphere trends. Results by month are difficult to interpret due to large fluctuations in the data. While age-incidence effects had no impact on the distribution of risk, we found an artefactual increase in January births due to routine imputation of missing birth dates. Conclusion: Adjusting for artefacts in the data produced a pattern analogous to northern hemisphere trends. [ABSTRACT FROM AUTHOR]

Objective: This paper reports on a study designed within the framework of the National Survey of Mental Health and Wellbeing to: estimate the prevalence of psychoses in urban areas of Australia; identify profiles of symptomatology, impairments and disabilities; collect information on services received and needed; and explore quality of life issues in a broadly representative sample of people with psychotic illnesses. Method: The study was conducted over four areas in the Australian Capital Territory, Queensland, Victoria and Western Australia, as a two-phase survey: (i) a census and screening for psychosis of all individuals who made contacts with mental health services during a period of 1 month in 1997; and (ii) interviews with a stratified random sample (n = 980) of the screen-positive individuals (n = 3800) using a standardised instrument. Results: The point prevalence (1 month) of psychotic disorders in the urban population aged 18–64 is in the range of 4–7 per 1000 with a weighted mean of 4.7 per 1000. People with psychotic disorders experience high rates of functional impairments and disability, decreased quality of life, persistent symptoms, substance-use comorbidity and frequent side effects of medication. Although the utilisation of hospital-based and community mental health services, as well as of public and non-governmental helping agencies, is high, the majority live in extreme social isolation and adverse socioeconomic circumstances. Among the many unmet needs, the limited availability of community-based rehabilitation, supported accommodation and employment opportunities is particularly prominent. Conclusions: The so-called ‘low-prevalence’ psychotic disorders represent a major and complex public health problem, associated with heavy personal and social costs. There is a need for a broad programmatic approach, involving various sectors of the community, to tackle the multiple dimensions of clinical disorder, personal... [ABSTRACT FROM AUTHOR]

The article focuses on a study on reform in the mental health services for schizophrenia and related psychotic disorders. Topics discussed include aspirations of young people for personal development and a meaningful life affected by the illness, stigmatizing stereotype of schizophrenia as a chronic disorder, and effects of diagnostic misclassification in the familial burden of psychotic disorders.

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, post‑neonatal 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. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine the association between lifetime cannabis use and estimates of both premorbid and current cognitive function in psychotic disorders in an Australian cohort.Methods: In an Australian multicenter cohort, 1237 participants with an established ICD-10 diagnosis of psychotic disorder were categorised according to history of lifetime cannabis use (non-users, n=354; cannabis users, n=221; cannabis dependency, n=662). Groups were analyzed according to available indices of cognitive ability: the National Adult Reading Test - Revised (NART-R) for ability prior to illness onset; and the Digit Symbol Coding Test (DSCT) for current ability. Two-way analysis of variance was conducted without any covariate, followed by a two-way analysis of covariance (using age, age at onset of psychiatric illness, premorbid IQ and the Socio-Economic Index for Areas (SEIFA) rankings).Results: Whilst there appeared to be a significant association between cannabis use and mean DSCT (higher DSCT scores in cannabis using groups) F(2,1080)=9.478, p<0.001, η2=0.017), once covariates were used in the analysis there were no significant differences between groups in mean DSCT scores (F(2,1011)=0.929, p=0.395, η2=0.002). Similarly there were no differences between groups in mean NART scores once, age, age at illness onset and SEIFA rankings were used as covariates (F(2,1032)=1.617, p=0.199, η2=0.003).Conclusions: Confounding variables underpin the association between cannabis use and cognitive function in psychotic disorders. Taken together, it would appear that cannabis use or dependence has no additive effect on cognitive dysfunction in these disorders. [ABSTRACT FROM AUTHOR]

Abstract: Background: We aimed to examine the association between illicit substance use and age at onset in psychotic disorders in an Australian cohort. Methods: Retrospectively acquired information on substance use during the year prior to illness onset was collected from 1642 participants enrolled in the Australian National 2010 Survey of High Impact Psychosis study (SHIP), with an ICD-10 diagnosis of schizophrenia spectrum or affective psychosis. Latent class analysis was performed according to illicit substance use, using age as an active covariate; identified classes were subsequently validated. Cox regression was used to examine the independent contribution of the identified substance use classes and several confounding variables to the prediction of age at onset of psychosis. Results: Three classes according to substance use were identified: non-users (n =803), cannabis predominant users (n =582), and polysubstance users (n =257). For participants with schizophrenia spectrum disorders, cannabis predominant users had a higher hazard of earlier age at onset than for non-users (adjusted HR=1.38, 95% CI=1.2–1.6); polysubstance users had an even higher hazard (adjusted HR=1.95, 95% CI=1.5–2.4). In contrast, for participants with affective psychosis, cannabis predominant users (adjusted HR=1.10, 95% CI=0.8–1.4) and polysubstance users (adjusted HR=0.87, 95% CI=0.6–1.3) did not have a higher hazard of earlier age at onset compared with non-users. Conclusions: Illicit substance use in the 12months prior to psychosis onset has a differential effect on age at onset in schizophrenia spectrum and affective psychotic disorders. Our findings are compatible with the notion that illicit drugs bring forward age at onset in schizophrenia spectrum disorders but not affective psychotic disorders. [Copyright &y& Elsevier]

Background: While there has been substantial research examining the correlates of comorbid substance abuse in psychotic disorders, it has been difficult to tease apart the relative importance of individual variables. Multivariate analyses are required, in which the relative contributions of risk factors to specific forms of substance misuse are examined, while taking into account the effects of other important correlates.Methods: This study used multivariate correlates of several forms of comorbid substance misuse in a large epidemiological sample of 852 Australians with DSM-III-R-diagnosed psychoses.Results: Multiple substance use was common and equally prevalent in nonaffective and affective psychoses. The most consistent correlate across the substance use disorders was male sex. Younger age groups were more likely to report the use of illegal drugs, while alcohol misuse was not associated with age. Side effects secondary to medication were associated with the misuse of cannabis and multiple substances, but not alcohol. Lower educational attainment was associated with cannabis misuse but not other forms of substance abuse.Conclusion: The profile of substance misuse in psychosis shows clinical and demographic gradients that can inform treatment and preventive research. [ABSTRACT FROM AUTHOR]

Abstract: Individuals with a psychotic disorder who had a premorbid history of amphetamine use (n =382) were analyzed in groups according to age of initiation to amphetamine (AIA) and mean number of years of duration of premorbid exposure to amphetamine (DPEA) was calculated. Univariate General Linear Models were used to test for group differences in age at onset of psychotic illness (AOI) and DPEA. Although a temporal direct relationship between AIA and AOI was detected (mean duration 5.3years), our findings suggested this association was spurious and better explained by a later initiation to amphetamine than to cannabis (by 2–3years). [Copyright &y& Elsevier]

Background Schizophrenia (SZ) is a clinically heterogeneous disorder with multifactorial causes including a significant genetic contribution. Recent, large scale GWAS have described a polygenic risk score (PRS) for SZ which accounts for ~ 7% of variation on the liability scale (Bulik-Sullivan et al, 2015). The aim of this study was to ascertain whether the PRS also contributed to a range of psychological measures which are associated with SZ. Methods Our cohort comprised a set of 127 multiplex families recruited through a proband with SZ (n=536 including 161 SZ cases) and a control group of 30 unaffected families (n=121). We examined neurocognitive measures across 6 domains: General cognitive ability (National Adult Reading Test & Shipley Institute of Living Scale IQ); verbal learning and memory (Rey Auditory Verbal Learning Test); sustained attention (Continuous Performance Task, degraded stimulus and identical pairs); speed of information processing (inspection time); executive function (Controlled Oral Word Association Task) and personality factors (Schizotypal Personality Questionnaire & Temperament and Character Inventory) (Hallmayer et al, 2005). Whole genome sequence (WGS) data (Illumina 10X platform, 15X coverage) were available for a subset of the multiplex families (n=320). We mapped all 102,636 PRS SNPs to the called WGS data by rsID; 97,507 passed QC and were used to calculate a PRS for each individual (Purcell et al, 2009). Correlation between PRS and each neurocognitive measure was conducted in SOLAR adjusting for the relationship matrix, age, sex and educational attainment. Results In the multiplex families, all psychological measures were associated with SZ in the expected direction (FDR corrected at α 0.05). Comparison with the control families showed that the Shipley measure of current IQ, and the identical pairs measure of sustained attention were significantly impaired in unaffected relatives of those with SZ compared the healthy control cohort (FDR-corrected at α 0.05) indicating a shared genetic component with SZ. PRS was significantly correlated with the identical pairs task, both inspection time tasks, and personality measures after FDR correction with the expected direction of effect. Discussion Recent studies have shown associations between PRS and neurocognitive measures in healthy populations, including IQ measures in a population based sample of children (Hubbard et al 2016) and working memory in young adults (Hatzimanolis et al 2015). Our findings add to these data and support the presence of shared common genetic factors between SZ and measures of sustained attention, speed of information processing and personality factors in a familial cohort with SZ. This information may help to inform the selection of endophenotypes for SZ. [ABSTRACT FROM AUTHOR]

Introduction Familial risk for psychosis may interact with environmental risk factors. Objectives We are studying a large birth cohort of children of mothers with psychotic disorders, themselves at high risk of developing a psychotic illness, to understand the developmental aetiology of psychotic illness. Aims Our aim is to examine whether exposure to environmental stressors in childhood, including timing of exposure, is a risk factor for psychotic illness, independent of familial liability. Specificity to maternal schizophrenia is explored. Methods We used record-linkage across state-wide registers (midwives, psychiatric, child protection and mortality, among others) to identify 15,486 offspring born in Western Australia 1980–2001 to mothers with a lifetime history of psychotic illness (case children) and compared them with 452,459 offspring born in the same period to mothers with no known psychiatric history (comparison children). Results A total of 4.1% of case children had developed a psychotic illness compared to 1.1% of comparison children. Exposure to environmental risk factors including obstetric complications, aboriginality, lower socioeconomic status, discontinuity in parenting and childhood abuse significantly increased risk of psychotic illness in offspring. Length and age at time of discontinuity in parenting impacted on risk. At the same time, case children were also significantly more likely than comparison children to be at risk of experiencing these adverse life events. Conclusions Exposure to environmental stressors is associated with psychotic illness, and timing of exposure is important. However, children already at increased familial risk for psychotic illness are also at increased risk of experiencing these environmental stressors. [ABSTRACT FROM AUTHOR]

Objective: There is a dearth of longitudinal data on outcomes in prevalent cases of psychotic illness across a range of ages and levels of chronicity. Our aim was to describe changes over time in mental and physical health outcomes, as well as patterns of service utilisation that may have influenced outcomes, in a representative prevalence sample of 641 Western Australians with a psychotic illness who, at Wave 1, were part of the National Survey of High Impact Psychosis., Methods: In Wave 1 (2010, 2012), a two-phase design was employed to ensure representativeness: Phase 1 psychosis screening took place in public mental health and non-government organisation services, while, in Phase 2, a randomised sample was interviewed. In Wave 2, 380/641 (59%) of participants were re-interviewed, with interviews staggered between 2013 and 2016 (follow-up time: 2.3-5.6 years). Data collection covered mental and physical health, functioning, cognition, social circumstances and service utilisation. Mental health outcomes were categorised as symptomatic, functional and personal recovery. Physical health outcomes covered metabolic syndrome and its component criteria., Results: In mental health, there were encouraging improvements in symptom profiles, variable change in functional recovery and some positive findings for personal recovery, but not quality of life. Participants ranked physical health second among challenges. Metabolic syndrome had increased significantly. While treatment for underlying cardiovascular risk conditions had improved, rates of intervention were still very low. More people were accessing general practices and more frequently, but there were sharp and significant declines in access to community rehabilitation, psychosocial interventions and case management., Conclusion: Although we observed some positive outcomes over time, the sharp decline in access to evidence-based interventions such as community rehabilitation, psychosocial interventions and case management is of great concern and augurs poorly for recovery-oriented practice. Changes in service utilisation appear to have influenced the patterns found.

Background: There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.AimsTo investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls., Method: Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls., Results: Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest., Conclusions: Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.Declaration of interestR.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

Objective: To investigate whether recent cannabis use by men and women with psychotic disorders was associated with increased risk of suicide attempt, and to determine associated factors, stratified by sex., Methods: Data from 1065 men and 725 women interviewed in the Australian national survey of psychosis were analysed to model separately, for each sex, the impact of daily, casual or no past-year cannabis use and other risk factors including age, on a past-year suicide attempt., Results: In the past year, 168 (9.4%) participants attempted suicide. Unadjusted analyses showed daily cannabis users of both sexes had significantly increased odds of attempting suicide compared to non-users. After adjusting for confounding factors, this relationship was no longer significant. Depression had the strongest association with attempting suicide for both sexes. Sex differences in other risk factors were observed. In post hoc analysis, daily cannabis use was associated with higher odds of attempting suicide in older men compared to non-users; this was not found in younger men or women., Conclusions: Associations between past-year cannabis use and suicide attempts were confounded by other factors (depression, loneliness, homelessness and hallucinations). The possibility of greater risk of suicidal behaviour with regular cannabis use for older men should be considered.

Cognitive impairment is a core feature of schizophrenia and impacts negatively the functioning of affected individuals. Cognitive decline correlates with aging, and is the primary cause of loss of independence and reduced quality of life. The klotho gene is a key modulator of aging, with expression deficiency resulting in premature aging, while overexpression extends lifespan and enhances cognition. A haplotype and functional human variant of the gene, KL-VS, increases expression and promotes longevity. KL-VS heterozygosity is associated with enhanced cognition and a larger volume of the right dorsolateral prefrontal cortex, a region involved in planning and decision-making, which is especially susceptible to shrinkage with age. We examined the effect of KL-VS heterozygosity on cognition in 497 schizophrenia patients and 316 healthy controls from the Western Australian Family Study of Schizophrenia (WAFSS) who had been comprehensively characterised by neurocognitive tests and classified into cognitively deficient (CD) and cognitively "spared" (CS) clusters. An older, cognitively normal population sample from the Health in Men Study (HIMS) was included to allow assessment of heterozygosity and memory in aged individuals. We show that heterozygosity is associated with better learning and memory in the younger WAFSS healthy controls but not in the aging HIMS sample. However, in schizophrenia patients, KL-VS has a selective effect on memory, with heterozygotes in CD and CS clusters performing worse than non-carriers. This effect was significant and more severe in the CD cluster, reinforcing the utility of subtyping patients into CD and CS clusters that may differ in their genetic underpinnings., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis., (© 2017 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.)

Objectives: The recently published RANZCP guidelines for schizophrenia and related disorders reviewed recent scientific evidence, and, where lacking, referred to clinical expertise to supply a template for raising the standard of care. This paper builds on the guidelines and recommends how they might be used to improve outcomes., Methods: The guidelines call for evidence-based mental health policies, inclusive of mobilising affected families, communities and the public in support of policies that ensure better care and protect the wellbeing of people with severe mental disorders. The process of preparing the guidelines highlighted the limits of our scientific understanding of schizophrenia and shortcomings in the care currently provided., Results: Writing the guidelines evinced the need for a culture of measuring outcomes and response to treatment, and harnessing such data to monitoring and optimising patient care., Conclusions: We recommend creation of a national case cohort for mental health research involving a collaborative network of clinical research centres, using the guidelines and generating scientific evidence for translation into clinical practice protocols that enable personalised treatment plans for patients and criteria for the performance of clinical services.

In a previous study we identified a relatively homogeneous subtype of schizophrenia characterized by pervasive cognitive deficit, which was the exclusive contributor to our findings of linkage to 6p25-p24. The 6p region contains Dysbindin (DTNBP1), considered to be one of the major schizophrenia candidate genes. While multiple studies have reported association between genetic variation in DTNBP1 and schizophrenia, the findings have been inconsistent and controversial, leading to recent calls for systematic re-examination and unambiguous evidence of association. To address this, we have undertaken a comprehensive survey of common genetic variation within DTNBP1 and its association with schizophrenia, using a HapMap-based gene-tagging approach. We genotyped 39 tSNPs in a sample of 336 cases and 172 controls of Anglo-Irish ancestry, with the phenotype defined as clinical schizophrenia, and as composite neurocognitive endophenotypes. Allele and haplotype frequencies, and LD structure in our control sample were similar to those in other European populations. Using multivariate generalized linear modeling, we observed no significant association between any tSNP and any outcome variable. Association with haplotypes was examined across the gene and in the previously associated 5' region. Neither global haplotype tests, nor specific analysis of the "risk" haplotype previously reported in an ethnically related population, the Irish high-density schizophrenia families, showed significant evidence of association with schizophrenia or with the neurocognitive endophenotypes in our sample. The framework and results of this study should facilitate further attempts at re-analysis of DTNBP1, in terms of standardized approaches to both phenotype definition and analysis of genetic variation.

Objective: To provide an overview of the development, approaches and main research projects of the Centre for Clinical Research in Neuropsychiatry (CCRN) in Perth, Western Australia., Method: Discursive., Results: Underlying concepts, methods and selected findings of recent research into the neurobiology and epidemiology of schizophrenia, autism and other psychotic disorders are presented., Conclusion: CCRN, one of Australia's youngest centres of psychiatric research, has invested fruitfully in research areas such as molecular genetics, neuropsychology, neurophysiology, behavioural pharmacology, diagnostic assessment procedures and record linkage epidemiology.

Background: Knowledge of the level of psychosocial impairment associated with psychosis is important in evaluating the impact of the illness on those affected. When such knowledge is derived from community-based epidemiological surveys, it can help in providing a public health perspective for service planning with information derived from representative samples of patients., Methods: A two-phase epidemiological survey of persons with psychosis in four predominantly urban areas of Australia. First phase screening for psychosis (N= 5,710) was followed by a semi-structured interview of a stratified random sample (N = 980) to assess psychopathology (lifetime and current) and psychosocial disability., Results: Most of the interviewees were unemployed and had never married. There was widespread impairment in sexual and social relationships and in the performance of activities of daily living. Over half expressed dissatisfaction with life in general. Persons with affective psychoses were often as disabled as those with schizophrenia and diagnostic categorizations were not important in the conferment of risk for disability. Rather, poor pre-morbid work or social adjustment and poor course of illness were potent risk factors for diverse forms of disability in persons with psychosis., Conclusion: A large proportion of persons with experience of psychosis living in the community suffers from significant levels of psychosocial disability. Disablement seems to reflect, in part, a diathesis of poor pre-morbid functioning and less than optimal response to treatment of the disorder.

Objective: To investigate the risk of suicide following contact with mental health services and whether it has changed over time., Method: Record linkage was used to obtain the records of previous hospital admissions and mental health service contacts for deaths due to suicide in the period 1980-98. Standardized incidence rates were calculated for the general population and for users of mental health services. Proportional hazards regression was used to assess risk factors within the cohort of people with mental health service contact., Results: Suicide risk was significantly increased in users of mental health services (rate ratio 6.66 in males and 7.52 in females). Suicide risk was highest in the first 7 days after discharge from in-patient care, and decreased exponentially with time since discharge. Suicide risk in users of mental health services has increased over the study period., Conclusion: These results highlight the importance of adequate follow-up of patients discharged from in-patient services, and the need for adequate resources for community-based services.

Objective: This paper reviews the historical and conceptual background to proposals about prevention of schizophrenia through intervention targeting asymptomatic, high-risk individuals. It also examines the outcomes of a hypothetical model of prevention based on a two-stage risk segmenting approach., Method: The assumptions and parameters used in the model are derived from actual epidemiological and clinical research. The two risk criteria selected are: (i) genetic risk (having a parent with schizophrenia); and (ii) neurocognitive deficit (abnormal performance on the Continuous Performance Task, CPT). The parameters and risk factors are applied to a hypothetical screening program covering a population of 100000., Results: At the end of the second stage of screening the program using the risk criteria to search for preventable cases will have correctly identified only three out of 20 'true' cases and will have incorrectly assigned to treatment two non-cases. The great majority of people at risk who will eventually develop schizophrenia are likely to remain undetected by current screening or preclinical diagnostic programs, while a certain number of people actually not at risk would be falsely identified as high-risk and offered treatment., Conclusions: Reliably identifying, with intention to treat, asymptomatic people in the community who are presumed to be at high risk of developing schizophrenia is at present epidemiologically non-viable. This caveat should not apply to strategies for early diagnosis and treatment of incipient episodes of schizophrenia where strategies to reduce the duration of untreated psychosis are likely to be both feasible and cost-effective.

Objective: To investigate the association between mental illness and cancer incidence, mortality and case fatality., Method: A population-based record linkage study was undertaken based on 172,932 patients of mental health services in Western Australia. Records of mental health service contacts were linked with cancer registrations and death records., Results: While there was little difference in overall cancer incidence rates between psychiatric patients and the general community (RR in males 1.05, 95%, CI 1.02-1.09, RR in females 1.02, 0.98-1.05), cancer mortality was 39%, higher in males (95%) CI: 32-46%) and 24% higher in females (17-32%)., Conclusion: People with mental illness in Western Australia do not show an increased incidence rate of cancer, but do have higher cancer mortality. This was attributed to a higher cancer case fatality rate among people with mental illness.