Perceived expressed emotion in individuals with a first episode of psychosis from a south Asian background.

AIM: To explore perceived expressed emotion in the south Asian context for individuals with a first episode of psychosis (FEP). METHOD: Semi-structured interviews were conducted with 16 service users experiencing a FEP to understand their experience of expressed emotion (EE) from their caregivers. Interviews were analysed using inductive thematic analysis. RESULTS: Four main categories were identified: connection and support, understanding and awareness, boundaries and independence and context and influence. Factors influencing perceived expressed emotion such as acceptance, acculturation, warmth and expressions of love, communication and family values were identified. Findings highlight south Asian's experiences of being cared for, and their perception of EE, including warmth and connection as a strength and resource. CONCLUSION: The findings shed light on culturally specific EE within the context of FEP that can be considered when working with south Asian communities within early intervention services. Findings highlight the impact of navigating and negotiating bicultural identities and generational differences in EE in the British south Asian context.

Pediatric traumatic brain injury as a risk factor for psychosis and psychotic symptoms: a systematic review and meta-analysis.

BACKGROUND: Psychosis is one of the most disabling psychiatric disorders. Pediatric traumatic brain injury (pTBI) has been cited as a developmental risk factor for psychosis, however this association has never been assessed meta-analytically. METHODS: A systematic review and meta-analysis of the association between pTBI and subsequent psychotic disorders/symptoms was performed. The study was pre-registered (CRD42022360772) adopting a random-effects model to estimate meta-analytic odds ratio (OR) and 95% confidence interval (CI) using the Paule-Mandel estimator. Subgroup (study location, study design, psychotic disorder v. subthreshold symptoms, assessment type, and adult v. adolescent onset) and meta-regression (quality of evidence) analyses were also performed. The robustness of findings was assessed through sensitivity analyses. The meta-analysis is available online as a computational notebook with an open dataset. RESULTS: We identified 10 relevant studies and eight were included in the meta-analysis. Based on a pooled sample size of 479686, the pooled OR for the association between pTBI and psychosis outcomes was 1.80 (95% CI 1.11-2.95). There were no subgroup effects and no outliers. Both psychotic disorder and subthreshold symptoms were associated with pTBI. The overall association remained robust after removal of low-quality studies, however the OR reduced to 1.43 (95% CI 1.04-1.98). A leave-one-out sensitivity analysis showed the association was robust to removal of all but one study which changed the estimate to marginally non-significant. CONCLUSIONS: We report cautious meta-analytic evidence for a positive association between pTBI and future psychosis. New evidence will be key in determining long-term reliability of this finding.

A systematic review of the effectiveness and implementation readiness of psychosocial interventions for psychosis in South Asia.

BACKGROUND: Little is known about the effectiveness and implementation of psychosocial interventions for psychosis in low- and middle-income countries (LMICs). In South Asia, specialist psychiatric resources are scarce. Support for psychosis often falls on the family or caregiver which can increase feelings of burden, impact caregivers' wellbeing, and increase mental health stigma. Psychosocial interventions are increasingly used for psychosis in South Asia and could reduce relapse and symptoms, reduce caregiver burden, conserve cost and resources. The aim of this review was to appraise the effectiveness and implementation readiness of psychosocial interventions for people with psychosis in South Asia. METHOD: A systematic search was conducted on MEDLINE, PsycINFO, Global Health, and Web of Science. The review was prospectively registered on PROSPERO (CRD42022329254). Studies were rated on two scales assessing quality and implementation readiness. RESULTS: Twenty-six papers were included, nine intervention-types including community-based interventions/assertive outreach; CaCBTp; FAP; psychoeducation; cognitive retraining/rehabilitation; social cognition/skills; family/ caregiver intervention; telehealth intervention; yoga-based intervention in six South Asian countries. Findings suggest a multicomponent community-based intervention (MCBI) was the most implementation ready due to its standardisation, good clinical outcomes for patients and caregivers, and training and cost evaluations. CONCLUSION: Of the included studies, MCBI and community-based outreach interventions utilising lay health workers appear to be the most implementation ready and are suggested to best address the treatment gap in South Asia.

Expressed emotion in the South Asian diaspora living in the UK: A qualitative study.

BACKGROUND: 'Expressed Emotion (EE)' captures ways in which emotions are expressed within a family environment. Research has found that EE in families has an impact on psychiatric illness, in particular psychosis, such that it increases risk of relapse. EE was conceptualised by research conducted in the UK. Thus, behaviours defined as pathological were largely based on white samples adhering to UK norms. Cross-cultural variations have been found in EE and its relationship with clinical outcomes. A more culturally appropriate understanding of norms surrounding the EE across cultures is required. AIMS: This study aims to use a bottom-up approach to provide a culturally specific understanding of family relationships and EE across 'non-clinical' UK-based South Asian families. METHODS: Semi-structured interviews were conducted with 18 South Asian participants to explore their relationships with a significant other. Interviews were analysed using thematic analysis. RESULTS: Four main themes were generated: expression of love, setting boundaries, inter-generational differences and acceptance. CONCLUSION: The findings indicate considerable cultural variability within EE and highlight the need to interpret EE in the context of socio-cultural norms. Whilst certain domains of EE that are considered pathological in Western contexts are present in the UK-based South Asian diaspora, these are perceived as less problematic, indicative of varying cultural norms.

Psychosis Endophenotypes: A Gene-Set-Specific Polygenic Risk Score Analysis.

BACKGROUND AND HYPOTHESIS: Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. STUDY DESIGN: We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. STUDY RESULTS: After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores. CONCLUSIONS: Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.

Exploring biomedical and traditional care pathways for people with psychosis in Karachi, Pakistan.

Background: Psychosis is known to have an adverse impact on an individual's quality of life, social and occupational functioning. A lack of treatment options for psychotic disorders such as schizophrenia contributes to adverse outcomes for individuals. A significant proportion of people with psychosis consult both formal and traditional routes of care. This warrants a need to explore perceptions around treatment options provided by diverse care providers, as the identification of avenues for support can improve psychiatric, alternative treatment and social outcomes. Methods: Focus groups discussions (FGDs) and in-depth interviews (IDIs) were used. Interactive Research and Development (IRD) research staff conducted 20 IDIs and 2 FGDs to obtain information about the perspectives, treatment pathways and experiences of individuals with psychosis, their caregivers, and service providers. Questions for clinician care providers and faith healers revolved around perceptions of psychosis, service users' background, subject knowledge and treatment, feedback and referral mechanisms, and promotion of services. A thematic analysis was used to analyze the interviews and coding was conducted on NVivo. Results: The results were categorized into five themes: perception of psychosis, experience of seeking/receiving care, assessment and diagnosis methods, promotion of services, and living with psychosis. Across service providers and patients, there was a wide variety of causes attributed to psychosis, and an overall lack of awareness regarding severe mental health conditions from both formal and informal care-providers. Biomedical treatment received mixed reviews, while some reported it as beneficial, the limited number of institutes and clinicians to cater for patients, stigma within society and care providers, the burden of caregiving, and misinformation from faith healers were all significant barriers to treatment. Conclusion: The results highlight the use of traditional healing practices for psychosis in Pakistan, which, coupled with inadequate referral mechanisms, present an opportunity to bridge the treatment gap between clinical and traditional healing practices through integration of treatment within community structures and systems. Better awareness of psychosis and its treatment methods, alongside interventions that reduce stigma could help facilitate help-seeking behavior and reduce the burden of caregiving.

Understanding experiences of mental health help-seeking in Arab populations around the world: a systematic review and narrative synthesis.

BACKGROUND: Racial and ethnic disparities in mental health service utilisation and access is well established. Mental illness is common among Arab populations globally, but most individuals display negative attitudes towards mental health and do not seek professional help. The aim of this systematic review was to determine 1) help-seeking behaviours 2) help-seeking attitudes and 3) help-seeking barriers and facilitators, related to mental health services among Arab adults. METHOD: A pre-defined search strategy and eligibility criteria allowed for database searching using terms related to: mental health, Arabs, help-seeking, as well as experiences and behaviours. Seventy-four articles were included and analysed through narrative synthesis. Results were reported using the PRISMA guidelines. The review protocol was registered prospectively on PROSPERO (CRD42022319889). RESULTS: Arabs across the world have negative attitudes towards formal help-seeking and are reluctant to seek help, despite the presence of psychological distress. There is little information on factors that influence help-seeking behaviours and rates of service use. Preference for informal help sources such as family and friends were expressed and considered more acceptable. Low mental health literacy, stigma, gender, age, education, religion, acculturation, and immigrant status were the most common factors influencing help-seeking attitudes. Barriers to help-seeking included stigma, privacy and confidentiality, trust, mental health literacy, language, logistics, and culture related barriers. Increasing societal and family awareness, external support and encouragement, shared culture between the client and therapist, quality of doctor patient relationship, and feelings of connectedness with the host country among refugees were mentioned facilitators. Mixed findings for the role of religion, and family and community, in relation to facilitating or hindering help-seeking were reported. CONCLUSIONS: There is an increased likelihood and preference to seek informal sources of psychological support among Arabs. Contextual and cultural factors impeding help-seeking for Arabs are common across the world. Future research should address actual utilisation rates of services to better understand factors that influence help-seeking behaviours and facilitators to help-seeking. Increasing mental health literacy and developing anti stigma campaigns is necessary. Developing culturally informed interventions should inform future efforts to promote help-seeking among this population.

Exploring the efficacy of a low intensity psychological intervention for family members and carers of individuals with a first episode of psychosis in early intervention services.

AIM: The study aimed to evaluate the efficacy, and explore carers' experience, of a brief carer focussed intervention in an Early Intervention in Psychosis (EIP) service using a mixed methods approach. METHODS: Carers within EIP services were invited to have the intervention, comprising a psychoeducation and wellbeing component, and 153 carers completed routine outcome measures including the Brief Experience of Caregiving Inventory (BECI), The Warwick-Edinburgh Mental Well-being Scale (WEMWEBS) and the Hospital Anxiety and Depression Scale (HADS) at baseline and after the completion of the intervention. Separately, nine carers took part in semi-structured interviews about their experience of the intervention. RESULTS: The intervention resulted in improvement of overall well-being, a reduction in self-reported anxiety and caregiving experience relating to difficult behaviours and stigma/effects on the family. Overall, the carers' subjective experiences of the intervention were positive. Thematic analysis indicated epistemic trust indexed by the connection carers achieved with the service, an experience of being valued and of experiencing change through the intervention. CONCLUSION: A short, 8 weeks intervention delivered by assistant psychologists, may offer an effective method for facilitating understanding of the illness and acclimatizing to new challenges. Exploring the effectiveness of psychoeducation and capturing this with specific measures may allow the service to make meaningful adaptations to their intervention.

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature.

INTRODUCTION: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. AIM: To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD METHODS: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. RESULTS: The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab. CONCLUSION: In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD.

Trends and Outcomes of Hospitalizations Due to Hemolytic Uremic Syndrome: A National Perspective.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a rare but challenging disease with varying degrees of mortality and prognosis. We aim to evaluate the trends and outcomes of hospitalizations due to HUS by utilizing a large population-based dataset. METHODS: We derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2007-2018. Our primary outcomes were in-hospital mortality, discharge disposition, and predictors of poor outcomes. We then utilized the Cochran Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors. RESULTS: A total of 8043 hospitalizations ranging from age zero to above 65 years of age occurred due to HUS from 2007-2018. The number of hospitalizations with HUS increased steadily from 528 in 2007 to 800 in 2013, but afterwards, we noticed a steady decline to 620 in 2018. Additionally, trends of in-hospital mortality slowly increased over the study period but we noticed a decline in the rate of discharge to skilled nursing facilities (SNFs). Furthermore, in multivariable regression analysis, predictors of increased mortality in hospitalized HUS patients were advanced age (95%CI: 1.221-1.686; p-value <0.0001) and requirement for dialysis (95%CI: 1.141-4.167; p-value: <0.0001). Advanced age >65 years (OR: 2.599, 95%CI: 1.406-4.803; p-value: 0.0023), as well as comorbidities such as diabetes mellitus and pulmonary circulatory diseases, which are under vascular events (OR: 1.467, 95%CI:1.075-2.000; p-value: 0.0156), were shown to have a higher rate of discharge to SNFs. Moreover, patients needing intravenous immunoglobulin (IVIG) and plasmapheresis had high odds of discharge to SNFs ((OR: 1.99, 95%CI: 1.307-3.03; p-value: 0.0013) and (OR: 5.509, 95%CI: 2.807- 10.809; p-value <0.0001), respectively), as well as smaller hospital bed size and hospital type (OR: 1.849, 95%CI: 1.142-2.993; p-value: 0.012). CONCLUSION: In this national representative study, we observed a total decrease in hospitalizations as well as discharge to SNFs; however we saw an increase in inpatient mortality. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.

Profiles and trajectories of mental health service utilisation during early intervention in psychosis.

BACKGROUND: Early intervention in psychosis services (EIS) support individuals experiencing a first episode of psychosis. Support required will vary in response to the remittance and reoccurrence of symptoms, including relapses. Characterising individuals who will need more intensive support can inform care planning. This study explores service utilisation profiles and their trajectories of service use in a sample of individuals referred to EIS. METHOD: We analysed service utilisation during the 3 years following referral to EIS (n = 2363) in West London between 2011 and 2020. Mental health service utilisation data were submitted to model-based clustering. Latent growth models were then estimated for identified profiles. Profiles were compared regarding clinical and demographic characteristics and onward pathways of care. RESULTS: Analyses revealed 5 profiles of individuals attending EIS based on their service utilisation over 3 years. 55.5% of the sample were members of a low utilisation and less clinically severe profile. The distinct service use patterns of these profiles were associated with Health of the Nations Outcome Scale scores at treatment initiation (at total, subscale, and individual item level), along with age and gender. These patterns of use were also associated with onward care and ethnicity. CONCLUSIONS: Profiles and trajectories of service utilisation call for development of integrated care pathways and use of more personalised interventions. Services should consider patient symptoms and characteristics when making clinical decisions informing the provision of care. The profiles represent typical patterns of service use, and identifying factors associated with these subgroups might help optimise EIS support.

Transitioning to age inclusive early intervention for psychosis.

AIM: Early Intervention in psychosis Services (EIS) have previously restricted access based on age. However, there is now a move to age inclusive service. We aimed to examine differences between early and late onset (>35 years) psychosis to see if a threshold was valid. We also investigated the potential of a statistical modelling method to identify group characteristics which may be missed using a descriptive approach. METHODS: Routine clinical data (n = 343), from an EIS, comprising socio-demographic, clinical, physical and treatment variables, were examined using descriptive and classification and regression tree (CART) analysis. RESULTS: The findings suggest that age differences were best explained by social factors. There was no emerging evidence that the differences exhibited had a fundamental impact on the clinical outcomes of the clients in terms of support beyond EIS (ie, hospitalization and home treatment team involvement) and pharmacological and psychological interventions. CART analysis revealed distinct service user characteristics associated with the clinical outcomes. CONCLUSION: There was no evidence to support a clinical cut off based on age providing support for age inclusive services. However, in the transition to age inclusive service delivery, EIS need to consider social/life stage variables, adapting provision where service delivery may operate a youth focused model. Routine analysis of clinical data should employ methods to identify groups of service users who may require adjusted service provision.

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Caregiving processes and expressed emotion in psychosis, a cross-cultural, meta-analytic review.

The construct of Expressed Emotion (EE) is a reliable predictor of relapse in psychotic disorders globally. However, cultural differences in the level and manifestation of EE have been reported. This review was conducted in line with PRISMA guidelines to demonstrate the distribution of EE and its domains cross-culturally as well as its relationship with relapse in psychosis. Ninety-six studies reported global EE scores and/or separate EE domains amongst caregivers of a family member with psychosis and used the Camberwell Family Interview (CFI) to measure EE. In the meta-analysis (k = 34, n = 1982), exposure to high EE was indicative of a 95% increased likelihood of relapse compared to low EE. However, no significant effect of geographical region on global EE scores (high/low) or EE domains was found. Several adjustments to the scoring of the CFI were highlighted based on cultural norms, particularly relevant to the domains of emotional over-involvement, warmth and criticism. Although this made meaningful quantitative comparisons across studies difficult, it nonetheless highlighted cultural considerations that need to be taken into account when interpreting EE and understanding its relationship to clinical outcomes. There is not a universal normative EE experience, with cultural variation in the scoring and interpretation of EE existing as evidenced by adjusted cut off scores and conceptualisation of EE constructs. Thus, it is important for clinical practitioners to have an awareness of different cultural norms in relation to caregiving and care receiving behaviours, which can inform adaptations to clinical interventions in multicultural settings.

Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders.

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.

The development and validation of the Brief Experience of Caregiving Inventory (BECI).

BACKGROUND: The social network supporting an individual with psychosis may be adversely affected by the experience of caregiving. The Experience of Caregiving Inventory (ECI) is 66 item self-report measure of the impact of caregiving for carers of people diagnosed with psychotic disorders. This study aimed to create a brief version of the ECI, and evaluate its reliability and validity (n = 626). METHODS: The validation process was conducted through a Multidimensional Item Response Theory (MIRT) approach, using a graded response model and a complementary network approach. RESULTS: This resulted in a 19 item, four factor inventory with a good model fit, displaying good reliability and validity. CONCLUSION: The BECI is a valid measure. The simplicity, ease of application and robust psychometric properties further enhances its acceptability and usefulness as a brief measure in clinical research and trials, as well as in routine practice providing reliable and valid data on experience of caregiving in families of an individual with psychosis.

A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains.

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.

Cross-Cultural Applicability of the Montreal Cognitive Assessment (MoCA): A Systematic Review.

The Montreal Cognitive Assessment (MoCA) is widely used to screen for mild cognitive impairment (MCI). While there are many available versions, the cross-cultural validity of the assessment has not been explored sufficiently. We aimed to interrogate the validity of the MoCA in a cross-cultural context: in differentiating MCI from normal controls (NC); and identifying cut-offs and adjustments for age and education where possible. This review sourced a wide range of studies including case-control studies. In addition, we report findings for differentiating dementias from NC and MCI from dementias, however, these were not considered to be an appropriate use of the MoCA. The subject of the review assumes heterogeneity and therefore meta-analyses was not conducted. Quality ratings, forest plots of validated studies (sensitivity and specificity) with covariates (suggested cut-offs, age, education and country), and summary receiver operating characteristic curve are presented. The results showed a wide range in suggested cutoffs for MCI cross-culturally, with variability in levels of sensitivity and specificity ranging from low to high. Poor methodological rigor appears to have affected reported accuracy and validity of the MoCA. The review highlights the necessity for cross-cultural considerations when using the MoCA, and recognizing it as a screen and not a diagnostic tool. Appropriate cutoffs and point adjustments for education are suggested.

Abnormal frontoparietal synaptic gain mediating the P300 in patients with psychotic disorder and their unaffected relatives.

The "dysconnection hypothesis" of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc.

Perceived ethnic discrimination and persecutory paranoia in individuals at ultra-high risk for psychosis.

Despite a consensus that psychosocial adversity plays a role in the onset of psychosis, the nature of this role in relation to persecutory paranoia remains unclear. This study examined the complex relationship between perceived ethnic discrimination and paranoid ideation in individuals at Ultra High Risk (UHR) for psychosis using a virtual reality paradigm to objectively measure paranoia. Data from 64 UHR participants and 43 healthy volunteers were analysed to investigate the relationship between perceived ethnic discrimination and persecutory ideation in a virtual reality environment. Perceived ethnic discrimination was higher in young adults at UHR in comparison to healthy controls. A positive correlation was observed between perceived ethnic discrimination and paranoid persecutory ideation in the whole sample. Perceived ethnic discrimination was not a significant predictor of paranoid persecutory ideation in the VR environment. Elevated levels of perceived ethnic discrimination are present in individuals at UHR and are consistent with current biopsychosocial models in which psychosocial adversity plays a key role in the development of psychosis and attenuated symptomatology.