Biopsychosocial Predictors of Paranoia in the Attenuated Psychosis Syndrome

Despite a consensus that psychosocial adversity plays a role in the onset of psychosis, the nature of this role and the underlying neurobiological mechanisms remain unclear. This study examined the complex relationship between perceived ethnic discrimination (PED) and paranoid ideation and its mediating factors, in individuals with Attenuated Psychotic Syndrome (APS) using a virtual reality paradigm to objectively quantify paranoia. Secondly, a sensory gating deficit, indexed by P50 Event Related Potential (ERP) abnormalities was examined, and the combined effect of electrophysiological sensory gating deficits and psycho-social adversity on the development of psychosis was explored. Results showed that perceived maternal neglect and antipathy in childhood, PED and perceived social support were key factors in young adults with APS. Also PED was positively correlated with persecutory paranoia. Furthermore, individuals with APS displayed sensory gating impairments. Therefore, perceived exposure to adverse experiences and sensory gating deficits observed in individuals with APS are present before the first episode and are consistent with current biopsychosocial models in which early psychosocial stress, later psychosocial adversity and neurocognitive functioning plays a key role in the development of psychosis

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

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

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

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

Abnormal P300 in people with high risk of developing psychosis

Background Individuals with an “at-risk mental state” (or “prodromal” symptoms) have a 20–40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable. Method 35 cases meeting PACE criteria for the at-risk mental state (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression. Results The P300 amplitude was significantly reduced in the ARMS group [8.6 ± 6.4 microvolt] compared to controls [12.7 ± 5.8 microvolt] (p < 0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Conclusion Reduction in the amplitude of the P300 is associated with an increased vulnerability to psychosis. Neurophysiological and other biological markers may be of use to predict clinical outcomes in populations at high risk

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.Funding: This work was funded by the Medical Research Council (G0901310), the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z), the European Union’s Seventh Framework Programme for research, technological development and demonstration (grant 602450). This study was also supported by the NIHR Biomedical Research Centre at University College London (mental health theme) and by the NIHR Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry – Kings College London. Further support: NHIR Academic Clinical fellowship awarded to M.S.C.. E.B. acknowledges research funding from: BMA Margaret Temple grants 2016 and 2006, MRC – Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry Kings College London. The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to C.I.). The BMA Margaret Temple grant 2016 to J. H.T. European Research Council Marie Curie award to A.D.-R. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental healthcare organisations. Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en de kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan Zorggroep, Prins Clauscentrum Sittard, RIAGG Roermond, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psychomedical center (The Hague). Utrecht: University Medical Center Utrecht and the mental health institutions Altrecht, GGZ Centraal, Riagg Amersfoort and Delta. The sample from Spain was collected at the Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Carlos III Health Institute PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005- Orden sco/3246/2004, SENY Fundació Research Grant CI 2005-0308007 and Fundación Marqués de Valdecilla API07/011. The present data were obtained at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: MINECO Exp.: SAF2013-46292-R

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

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