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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., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Loneliness is an established risk factor for poor cardiometabolic health. People with psychotic disorders experience high rates of both cardiometabolic disease and loneliness, but how these factors are associated is poorly understood. Thus, using data from the second Australian National Survey of Psychosis we examined whether loneliness is associated with the likelihood of cardiometabolic disorder in psychotic illness. Loneliness was assessed using a single-item measure, with a 4-point scale (not lonely; lonely occasionally; some friends but lonely for company; socially isolated and lonely) whilst cardiometabolic status was assessed in terms of the criteria used to determine metabolic syndrome (elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose). Logistic regression was employed to examine whether loneliness was associated with metabolic syndrome status, and its individual components, with and without adjustment for confounding variables. Increased loneliness was associated with an increased risk of metabolic syndrome in people with psychosis (OR 1.21, 95% CI 1.08-1.36, p < .001) and to the risk of elevated waist circumference (p < .01), elevated triglycerides (p < .05) and reduced high-density lipoprotein cholesterol (p < .05). Notably, these associations largely persisted when controlling for a range of covariates. Feeling lonely is significantly associated with metabolic syndrome, and dyslipidemia specifically, in people with psychotic disorders. These data suggest that the potential benefits of interventions to reduce loneliness in psychosis may extend to cardiovascular as well as psychosocial functioning, and should be explored in future research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Schizotypal traits are expressions of underlying vulnerability to psychotic disorders which have a potential impact on mental health status, neurocognition, quality of life, and daily functioning. To date, little research has examined epidemiologic landscape of schizotypal traits at the cross-national level. Our aim was to study the expression of schizotypal traits by sex, age, and country in a combined sample gathered from 12 countries., Methods: A total of 27,001 participants completed the Schizotypal Personality Questionnaire (SPQ). The mean age of participants was 22.12 (SD=6.28); 37.5% (n=10,126) were males., Results: Schizotypal traits varied according to sex, age, and country. Females scored higher than males in the positive dimension, whereas males scored higher in the disorganization dimension. By age, a significant decrease in the positive schizotypal traits was observed. Epidemiological expression of schizotypal traits varied by country. Moreover, several interactions by sex, age, and country were found., Conclusions: This pattern is similar to those found in patients with psychosis and psychotic-like experiences. These findings provide new insights and the opportunity to explore the phenotypic expression of schizotypal traits at cross-national level., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Schizotypal Personality Questionnaire-Brief (SPQ-B) was developed with the aim of examining variations in healthy trait schizotypy, as well as latent vulnerability to psychotic-spectrum disorders. No previous study has studied the cross-cultural validity of the SPQ-B in a large cross-national sample. The main goal of the present study was to analyze the reliability and the internal structure of SPQ-B scores in a multinational sample of 28,426 participants recruited from 14 countries. The mean age was 22.63years (SD=7.08; range 16-68years), 37.7% (n=10,711) were men. The omega coefficients were high, ranging from 0.86 to 0.92 for the total sample. Confirmatory factor analysis revealed that SPQ-B items were grouped either in a theoretical structure of three first-order factors (Cognitive-Perceptual, Interpersonal, and Disorganized) or in a bifactor model (three first-order factors plus a general factor of schizotypal personality). In addition, the results supported configural but not strong measurement invariance of SPQ-B scores across samples. These findings provide new information about the factor structure of schizotypal personality, and support the validity and utility of the SPQ-B, a brief and easy tool for assessing self-reported schizotypal traits, in cross-national research. Theoretical and clinical implications for diagnostic systems, psychosis models, and cross-national mental health strategies are derived from these results., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The exome array assays rare-but-recurrent, likely deleterious, exonic variants and represents an intermediary between single nucleotide polymorphism (SNP) arrays and sequencing for genetic association studies. Multiplex families with multiple affected individuals may be enriched for disease-associated variants of this class compared to unrelated populations. We present an exome array study of schizophrenia in 99 multiplex families (n=341, including 118 cases) from the Western Australian Family Study of Schizophrenia (WAFSS). Compared to 55,726 individuals from the DIAGRAM sample not selected for schizophrenia, overall allele frequency of exome variants was higher in the WAFSS (P<2.2E-16). This was pronounced in variants nominally associated (P<0.05) with schizophrenia. Genes harbouring variants present only in WAFSS cases were enriched (FDR-corrected P=0.05) for membership of the 'extracellular matrix (ECM) - receptor interaction' biological pathway, adding to evidence that processes affecting the composition or turnover of ECM may contribute to neuropsychiatric disease. We did not find individual variants significantly associated with schizophrenia, although like previous studies, power to detect associations of small effect size was low. Cases did not exhibit a higher burden of variants compared to their unaffected relatives and the finding of previous exome chip studies of unrelated samples that 'schizophrenia gene-sets' were enriched for case-only variants was not replicated in the WAFSS. The higher frequency of moderately rare, exonic variants in these multiplex families compared to a population-based sample may account for some of their genetic liability to schizophrenia, and adds to evidence for a role of exome array variants from previous studies of unrelated samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Loneliness involves subjective, rather than objective, social isolation and has a range of negative effects on mental and physical functioning. The purpose of this study was to examine the prevalence of loneliness in psychotic disorders and its association with symptoms and cognitive performance., Method: Data were drawn from the second Australian National Survey of Psychosis and comprised responses from 1642 participants with an International Classification of Diseases 10 diagnosis of psychotic disorder who had completed a semi-structured interview of symptoms and social functioning (including loneliness), along with standardized assessments of current (digit symbol coding; DSC) and premorbid (National Adult Reading Test) cognitive ability. We examined the prevalence of loneliness across the diagnostic categories of psychosis, and its association with psychotic and non-psychotic symptoms and digit symbol coding scores., Results: The prevalence of loneliness was high, ranging from 74.75% in participants with delusional disorders to 93.8% in depressive psychosis, and was significantly higher than in the general population. Loneliness was also significantly associated with anhedonia and subjective thought disorder. Participants feeling socially isolated/lonely for company had significantly lower DSC scores than those who only felt lonely occasionally. Unexpectedly, participants who reported not feeling lonely had the lowest DSC scores., Conclusions: Loneliness is common across all psychotic disorders, particularly in depressive psychosis. It is specifically associated with ongoing loss of pleasure and disordered thoughts as well as impairment in current cognitive functioning. However, poor cognitive functioning is not inevitably associated with loneliness. Implications for personalized treatment of psychosis are discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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., (Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.)

Background: Formal thought disorder (TD) is a key symptom of schizophrenia with a significant impact on interpersonal relationships. Current cognitive models emphasize disordered language functioning and abnormalities accessing semantic representations. The cortical mechanisms for language and motor function are closely linked, hence action-related language may be impaired in TD, yet existing studies have focussed exclusively on object (noun) rather than action (verb) semantics., Method: In order to examine this issue both action (verb) and traditional semantic (tools, fruits, musical instruments) and phonological (FAS) fluency tasks were completed by individuals with schizophrenia (N=53) and healthy controls (N=69). Fluency performance was measured as the total number of correct words generated in 60s. The Schizotypal Personality Questionnaire (SPQ) was used to index odd and disorganized speech, as well as positive and negative symptoms., Results: Fluency on all tasks was impaired in schizophrenia, compared to controls, with a similar effect size. Within the schizophrenia group Odd Speech was correlated with poor fluency for actions, tools and musical instruments but not fruit or phonological fluency. These action-related fluency deficits were also correlated with Constricted Affect and Social Anxiety but not with Unusual Perceptions/Odd Beliefs., Conclusion: These results point to a unique connection and possible common aetiology between action fluency and odd speech in schizophrenia rather than a general impairment in language/executive functions common to fluency tasks. The findings provide the first evidence of a specific role of action-based language production deficits in TD together with a joint effect on social interaction skills., (Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.)

Background: Visuospatial working memory is not a unitary sketch pad but comprises independent dimensions of target distance and direction and at least two levels of detail (fine-grained and category level). The aim of this study was to examine these multiple aspects of encoding in patients with schizophrenia using a modified delayed response task., Method: 42 patients with schizophrenia and 48 healthy controls pointed, as accurately as possible from a fixed starting position, to the visual location of target stimuli presented to a touch-sensitive screen. An adaptive staircase procedure was used to equate stimulus duration for each individual. Encoding accuracy and maintenance of distance (mm) and direction ( degrees ) information was examined following a 0-second (immediate) or 4-second (unfilled) delay. Analyses utilized both absolute (unsigned) and signed data., Results: The results showed that the average duration required to detect a target was significantly longer in patients than controls. When stimulus duration was equated, (a) the absolute accuracy of distance and direction responses was not significantly different between groups at 0-second delay but was significantly reduced at 4-second delay in patients with schizophrenia, and (b) signed direction errors at 4-second delay were significantly different between groups at stimulus angles greater than 90 degrees ., Conclusions: The findings challenge previous suggestions of deficits in fine-grained encoding of spatial information in schizophrenia but confirm a difficulty maintaining both direction and distance details in working memory. Imprecision in spatial memory in schizophrenia also introduced greater bias from category level (prior) representations, especially in left hemi-space.

The current study aimed to provide evidence for the context-memory hypothesis, which proposes that schizophrenia is linked to a deficit in retrieving contextual information and in binding the different components of a memory together. A new task was developed in which memory for the content of events could be assessed in conjunction with memory for both source and temporal information. Forty-three patients with schizophrenia and 24 normal controls took part in the study. Patients were found to be less accurate in identifying the source and temporal context of events. Furthermore, whereas controls tended to identify correctly both source and temporal context of events, patients tended to have a more fractionated recollection of those events. The study provides support for the context-memory hypothesis by demonstrating that patients with schizophrenia show a fundamental deficit in binding contextual cues together to form a coherent representation of an event in memory.

The study investigated whether auditory hallucinations (AH) in schizophrenia are linked to a deficit in inhibition. Two tasks assessing the intentional suppression of cognitive events-the Hayling Sentence Completion Test (HSCT) [Neuropsychologia 34 (1996) 263] and the Inhibition of Currently Irrelevant Memories Task (ICIM) [Nature Neuroscience 2 (1999) 677]-were administered to 42 patients with schizophrenia and 24 normal controls. Presence and severity of symptoms in the patient group were examined using the Positive and Negative Syndrome Scale (PANSS). Patients performed significantly worse on the measures of inhibition compared to controls. More importantly, among patients, significant positive correlations were obtained between an index of AH severity (defined as an increase in frequency of AH on PANSS) and the number of type A errors on the HSCT and errors in the last three runs of the ICIM. An increase in AH severity was, therefore, associated with increasingly impaired control of intentional inhibition. Furthermore, no significant correlations were found between these indices of inhibition and either negative, general or positive symptoms (excluding AH scores).