Exploring the relationship between frequent cannabis use, belief updating under uncertainty and psychotic-like symptoms.

Background: Cannabis users present an important group for investigating putative mechanisms underlying psychosis, as cannabis-use is associated with an increased risk of psychosis. Recent work suggests that alterations in belief-updating under uncertainty underlie psychosis. We therefore compared belief updating under uncertainty between cannabis and non-cannabis users. Methods: 49 regular cannabis users and 52 controls completed the Space Game, via an online platform used for behavioral testing. In the task, participants were asked to predict the location of the stimulus based on previous information, under different uncertainty conditions. Mixed effects models were used to identify significant predictors of mean score, confidence, performance error and learning rate. Results: Both groups showed decreased confidence in high noise conditions, and increased belief updating in more volatile conditions, suggesting that they could infer the degree and sources of uncertainty. There were no significant effects of group on any of the performance indices. However, within the cannabis group, frequent users showed worse performance than less frequent users. Conclusion: Belief updating under uncertainty is not affected by cannabis use status but could be impaired in those who use cannabis more frequently. This finding could show a similarity between frequent cannabis use and psychosis risk, as predictors for abnormal belief-updating.

Differential inflammatory profiles in carriers of reciprocal 22q11.2 copy number variants.

BACKGROUND: Genetic copy number variants (CNVs; i.e., a deletion or duplication) at the 22q11.2 locus confer increased risk of neuropsychiatric disorders and immune dysfunction. Inflammatory profiles of 22q11.2 CNV carriers can shed light on gene-immune relationships that may be related to neuropsychiatric symptoms. However, little is known about inflammation and its relationship to clinical phenotypes in 22q11.2 CNV carriers. Here, we investigate differences in peripheral inflammatory markers in 22q11.2 CNV carriers and explore their relationship with psychosis risk symptoms and sleep disturbance. METHODS: Blood samples and clinical assessments were collected from 22q11.2 deletion (22qDel) carriers (n=45), 22q11.2 duplication (22qDup) carriers (n=29), and typically developing (TD) control participants (n=92). Blood plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and anti-inflammatory cytokine interleukin-10 (IL-10) were measured using a MesoScale Discovery multiplex immunoassay. Plasma levels of C-reactive protein (CRP) were measured using Enzyme-linked Immunosorbent Assay (ELISA). Linear mixed effects models controlling for age, sex, and body mass index were used to: a) examine group differences in inflammatory markers between 22qDel, 22qDup, and TD controls, b) test differences in inflammatory markers between 22qDel carriers with psychosis risk symptoms (22qDelPS+) and those without (22qDelPS-), and c) conduct an exploratory analysis testing the effect of sleep disturbance on inflammation in 22qDel and 22qDup carriers. A false discovery rate correction was used to correct for multiple comparisons. RESULTS: 22qDup carriers exhibited significantly elevated levels of IL-8 relative to TD controls (q<0.001) and marginally elevated IL-8 levels relative to 22qDel carriers (q=0.08). There were no other significant differences in inflammatory markers between the three groups (q>0.13). 22qDelPS+ exhibited increased levels of IL-8 relative to both 22qDelPS- (q=0.02) and TD controls (p=0.002). There were no relationships between sleep and inflammatory markers that survived FDR correction (q>0.14). CONCLUSION: Our results suggest that CNVs at the 22q11.2 locus may have differential effects on inflammatory processes related to IL-8, a key mediator of inflammation produced by macrophages and microglia. Further, these IL-8-mediated inflammatory processes may be related to psychosis risk symptoms in 22qDel carriers. Additional research is required to understand the mechanisms contributing to these differential levels of IL-8 between 22q11.2 CNV carriers and IL-8's association with psychosis risk.

Understanding the Psychosis Spectrum Using a Hierarchical Model of Social Cognition.

BACKGROUND AND HYPOTHESIS: Social cognitive impairments are central to psychosis, including lower severity psychosis-like experiences (PLEs). Nonetheless, progress has been hindered by social cognition's poorly defined factor structure, as well as limited work examining the specificity of social cognitive impairment to psychosis. The present study examined how PLEs relate to social cognition in the context of other psychopathology dimensions, using a hierarchical factors approach to social cognition. STUDY DESIGN: Online community participants (N = 1026) completed psychosis, autism, and personality disorder questionnaires, as well as 3 social cognitive tasks that varied in methodology (vignette vs video) and construct (higher- vs lower-level social cognition). Exploratory (EFA) and confirmatory factor analyses (CFA) were used to model social cognition, with the best models being examined in association with PLEs and psychopathology dimensions. STUDY RESULTS: EFA and CFA supported a hierarchical model of social cognition, with 2 higher-order factors emerging: verbal/vignette task methodology and a multimethod general social cognition factor. These higher-order factors accounted for task-level associations to psychopathology, with relations to positive symptoms (r = .23) and antagonism (r = .28). After controlling for other psychopathology, positive symptoms were most clearly related to tasks with verbal methodology (ß = -0.34). CONCLUSIONS: These results suggest that broad social cognitive processes and method effects may account for many previous findings in psychosis and psychopathology research. Additionally, accounting for broad social cognitive impairment may yield insights into more specific social cognitive processes as well.

Impulsivity as a predictor of clinical and psychological outcomes in a naturalistic prospective cohort of subjects at ultra-high risk (UHR) for psychosis from Tunisia.

BACKGROUND: Impulsivity is associated with serious detrimental consequences on physical, mental, behavioral and social aspects of health among patients with psychosis. The present prospective 12-month follow-up study aimed to determine the prevalence of highly impulsive individuals among Ultra High Risk (UHR) patients, how impulsivity evolves over the follow-up period, and whether impulsivity impacts clinical, psychological and functional outcomes in this population. METHOD: UHR patients were invited to complete a battery of measurements at three-time points: at baseline, and at 6 and 12 months of follow-up. Impulsivity was assessed using both behavioral (the Wisconsin Card Sorting Test, WCST) and self-report (the Barratt Impulsiveness Scale, BIS-11) measures. RESULTS: Findings showed that at 6 months of follow-up, higher 6-month BIS-11 attentional and motor impulsivity were significantly associated with lower quality of life and greater general psychological distress. In addition, higher baseline BIS-11 motor impulsivity significantly predicted more severe positive psychotic symptoms at 12 months of follow-up. However, WCST scores did not show any significant associations with study variables at the different times of follow-up. CONCLUSION: Interventions targeting impulsivity in UHR individuals could help decrease psychological distress and positive psychotic symptoms' severity, as well as improve quality of life in UHR individuals.

Social Cognition and Functional Connectivity in Early and Chronic Schizophrenia.

BACKGROUND: Individuals with schizophrenia (SZ) experience impairments in social cognition that contribute to poor functional outcomes. However, mechanisms of social cognitive dysfunction in SZ remain poorly understood, which impedes the design of novel interventions to improve outcomes. This pre-registered project (https://doi.org/10.17605/OSF.IO/JH5FC) examines the representation of social cognition in the brain's functional architecture across early and chronic SZ. METHODS: The study contains two parts: a confirmatory and an exploratory portion. In the confirmatory portion, we identified resting-state connectivity disruptions evident in early and chronic SZ. We performed a connectivity analysis using regions associated with social cognitive dysfunction in early and chronic SZ to test whether aberrant connectivity observed in chronic SZ (N=47; HC=52) was also present in early SZ (N=71, HC=47). In the exploratory portion, we assessed the out-of-sample generalizability and precision of predictive models of social cognition. We used machine learning to predict social cognition and established generalizability with out-of-sample testing and confound control. RESULTS: Results reveal decreases between left inferior frontal gyrus and intraparietal sulcus in early and chronic SZ, which are significantly associated with social and general cognition and global functioning in chronic SZ and with general cognition and global functioning in early SZ. Predictive modeling reveals the importance of out-of-sample evaluation and confound control. CONCLUSION: This work provides insights into the functional architecture in early and chronic SZ and suggests that IFG-IPS connectivity could be a prognostic biomarker of social impairments and a target for future interventions (e.g. neuromodulation) focused on improved social functioning.

A systematic review and meta-analysis of the traumatogenic phenotype hypothesis of psychosis.

BACKGROUND: Developmental trauma increases psychosis risk and is associated with poor prognosis. It has been proposed that psychosis in survivors of developmental trauma gives rise to a distinct 'traumatogenic' phenotype. AIMS: Given the implications for personalised treatment, we sought to explore the traumatogenic psychosis phenotype hypothesis in a systematic review and meta-analysis of studies comparing psychotic presentations between adults with and without developmental trauma histories. METHOD: We registered the systematic review on PROSPERO (CRD42019131245) and systematically searched EMBASE, Medline and PsycINFO. The outcomes of interests were quantitative and qualitative comparisons in psychotic symptom expression (positive, negative, cognitive) and other domains of psychopathology, including affect regulation, sleep, depression and anxiety, between adults with and without experience of developmental trauma. RESULTS: Of 34 studies included (N = 13 150), 11 were meta-analysed (n = 2842). A significant relationship was found between developmental trauma and increased symptom severity for positive (Hedge's g = 0.27; 95% CI 0.10-0.44; P = 0.002), but not negative symptoms (Hedge's g = 0.13; 95% CI -0.04 to 0.30; P = 0.14). Developmental trauma was associated with greater neurocognitive, specifically executive, deficits, as well as poorer affect, dissociation and social cognition. Furthermore, psychotic symptom content thematically related to traumatic memories in survivors of developmental trauma. CONCLUSIONS: Our findings that developmental trauma is associated with more severe positive and affective symptoms, and qualitative differences in symptom expression, support the notion that there may be a traumatogenic psychosis phenotype. However, underdiagnosis of post-traumatic stress disorder may also explain some of these findings. More research is needed to explore this further.

DNA methylation at cannabinoid type 1 and dopamine D2 receptor genes in saliva samples of psychotic subjects: is there an effect of Cannabis use?

Psychosis is a characterizing feature of many mental disorders that dramatically affects human thoughts and perceptions, influencingthe ability to distinguish between what is real and what is not. Both genetic and environmental factors, such as stressful events or drug use, play a pivotal role in the development of symptomatology and therefore changes in the epigenome may be of relevance in modeling a psychotic phenotype. According to the well-documented dysregulation ofendocannabinoid and dopaminergic system genes in schizophrenia, we investigated DNA methylation cannabinoid type 1 receptor (CNR1) and dopamine D2 receptor (DRD2) genes in saliva samples from psychotic subjects using pyrosequencing. The epigenetic mark was significantly higher and directly correlated for both genes in psychotic subjects compared to healthy controls. We also showed that these DNA methylation levels were lower in psychotic subjects reporting current delta-9-tetrahydrocannabinol (THC) consumption, a well-known risk factor for developing psychosis throughout the lifespan, resembling those of controls at least for the DRD2 gene. Overall, our data confirm the key role of CNR1 and DRD2 gene regulation in psychosis and suggest DNA methylation levels at specific CpG sites as potential biomarkers, but just in those psychotic subjects not consuming THC.

Retrospective Review of Postpartum Lithium Use Including During Lactation.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% (n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% (n = 11), initiated lithium prior to pregnancy, 11% (n = 2) initiated during pregnancy and 27% (n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants,;average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Exacerbation of delirium and epileptic seizures in an older man with idiopathic Parkinson's disease due to multiple prescriptions: a case report.

Introduction: Parkinson's disease (PD) is a disorder characterized by motor symptoms, such as rigidity, akinesia, and resting tremor, as well as non-motor symptoms, including psychiatric manifestations and autonomic failure. The prevalence of PD increases with age, and the condition is more common in men than in women. Conversely, polypharmacy has emerged as a paramount medical concern, especially among older patients, correlating with medicines' adverse effects, interactions between medicines, frequent admissions to the hospital, and a high risk of morbidity and mortality. Case description: We encountered an older male patient with idiopathic PD and mild renal dysfunction. Originally prescribed 14 types of medicines, including anti-PD drugs, the patient developed delirium and epileptic seizures during hospitalization. After reducing the number of medications, including amantadine, the symptoms significantly improved. This clinical course suggests that polypharmacy, in addition to PD itself, poses a significant risk of delirium and epileptic seizures, even in patients with mild renal dysfunction. Conclusion: This report is indicative of the risk of polypharmacy and highlights the importance of citing drug interactions for a correct diagnosis in patients presenting with complex symptoms.

Effectiveness of pharmacological treatments for severe agitation in real-world emergency settings: protocol of individual-participant-data network meta-analysis.

BACKGROUND: Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision. METHODS: We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. DISCUSSION: This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023402365.

Development of an early intervention in psychosis services fidelity questionnaire.

PURPOSE: We describe the development of an online fidelity questionnaire for early intervention in psychosis (EIP) services, to be used in population-level research, and that can be completed using self-reports from EIP staff. METHODS: A review of key literature sources on the components of EIP services was used to identify those components eligible for inclusion in the questionnaire. A modified Delphi approach, using experts in EIP services, was used to select the most important components to include in the questionnaire. To pilot test the questionnaire, two EIP staff members completed one fidelity questionnaire each, and a third questionnaire was completed by an external rater. Responses from the three sources were compared and used to revise the fidelity questionnaire. RESULTS: Twenty-two experts from England and Canada responded to two Delphi rounds, identifying the top 25 most important EIP service components. Some evidence-based components were not rated as highly as some non-evidence-based components. Pilot testing showed that the EIP staff rated fidelity higher than the external rater. Several questions were removed and/or revised based on the pilot study findings. CONCLUSIONS: Fidelity instruments are limited by the available evidence and the personal experiences of experts used to develop them. As such, fidelity instruments and EIP services should continually be updated to reflect new knowledge. The online fidelity questionnaire was a simple and efficient way to collect data. Future evaluations of the fidelity questionnaire need to ensure that externally collected fidelity data are comprehensive and accurate.

Preliminary evaluation of a questionnaire for assessing fidelity of early intervention for psychosis services.

PURPOSE: Fast, easy, and cost-effective methods are needed for fidelity assessment, quality improvement initiatives, and population-based studies in Early Intervention for Psychosis (EIP) services. Having an online questionnaire assessing the fidelity of EIP services, completed by staff self-reports, and having evidence of reliability and validity, could fill that gap. We assess the reliability and validity of the Early Intervention for Psychosis Services Fidelity Questionnaire (EIPS-FQ), developed in Part I of this set of papers. METHODS: A convenience sample of 10 EIP teams in England was used. Two staff members completed online questionnaires assessing recent and past fidelity. An external rater completed the same questionnaire for the two time periods, using a random sample of patient medical records, program documentation, and interviews with staff. The intra-class correlation coefficient (ICC) was calculated to assess inter-rater reliability. Validity was assessed using Bland-Altman plots, absolute mean differences, and the ICC. RESULTS: The fidelity score measuring recent fidelity ranged from 54.2 to 82.7, out of a possible 100. The ICC assessing reliability of the fidelity score was 0.40 (95% CI: 0.0-0.81). The ICCs for the fidelity sub-category scores ranged from 0 to 0.76. Two sub-categories, comprehensive assessments and family involvement and intervention, had low ICCs, regardless of period examined. CONCLUSIONS: This first attempt at validating the EIPS-FQ has demonstrated that the reliability of the EIPS-FQ is moderate/low, and therefore requires modification prior to use. The next iteration of the fidelity questionnaire will clarify or remove items which had very low fidelity and add evidence-based components not identified in the Delphi exercise.

Successful Lorlatinib Rechallenge After Severe Drug-Induced Psychosis in ALK-Positive Metastatic NSCLC: A Case Report.

Neurocognitive adverse events (NAEs) have been reported in up to 60% of patients on lorlatinib, a potent central nervous system-active ALK inhibitor. Manifestations may include psychotic, mood, speech, and cognitive symptoms. Current guidance recommends permanent discontinuation of lorlatinib in cases of grade IV NAEs. Here, we report a case of successful rechallenge of dose-reduced lorlatinib after recovery of grade IV psychosis in a patient with ALK-positive NSCLC.

The Complex Pattern Mismatch Negativity as a Potential Indicator of Psychosis Across all Phases of Illness: A Meta-Analysis.

Over the past decade, there has been extensive research on the mismatch negativity (MMN) and its promise as a biomarker of illness in people with schizophrenia (SZ). Nevertheless, when attempting to assess the early stages of illness progression, the utility of MMN has been inconsistent. Recently, researchers have been investigating a more advanced MMN paradigm (the complex MMN [cMMN]) which is believed to index higher-order cognitive processing and has been suggested to be a more effective indicator of the early phases of SZ. The cMMN is defined as a paradigm that relies on alterations within a pre-established pattern of stimuli. In this meta-analysis, we investigated cMMN deficits in individuals with SZ, including an analysis involving those in the first 5 years of illness. Our search also included individuals with bipolar disorder who experience psychosis; however, no related papers were found and thus, no findings are reported. Our findings indicate a small/moderate effect (d = 0.47), suggesting that individuals with SZ exhibit reduced cMMN amplitudes compared to individuals without SZ. Interestingly, this effect seems to be more pronounced in individuals within the first 5 years of their illness (d = 0.58), suggesting that cMMN might be a more sensitive biomarker in the early phases of SZ compared to traditional paradigms.

Does social isolation predict the emergence of psychotic-like experiences? Results from the experience sampling method study.

BACKGROUND: Several studies have shown that social isolation and loneliness are associated with the occurrence of psychotic experiences. However, dynamics of these phenomena in people with subclinical experiences, commonly referred to as psychotic-like experiences (PLEs), remains largely unknown. Therefore, in this study we performed a temporal network analysis to model dynamic predictions between social isolation, loneliness, negative affect, social stress, and PLEs. METHODS: A total of 77 drug-naïve individuals with PLEs from a transdiagnostic sample were enrolled. Data were obtained using the experience sampling method (ESM). The ESM questionnaires were delivered during 7 consecutive days (6 assessments per day). Therefore, 3234 data entries were analyzed. RESULTS: Social isolation predicted next-moment emergence of PLEs through the effects on loneliness and negative affect. Also, PLEs appeared to predict next-moment loneliness, but not social isolation, through the effects on negative affect. Social stress did not predict any variables in the network. However, it was predicted by previous-moment PLEs and social isolation. Negative affect had the highest in-strength and out-strength centrality. CONCLUSIONS: Findings from the present study indicate that social isolation might predict the emergence of PLEs through the effects of momentary loneliness and negative affect. Also, loneliness might be bidirectionally associated with PLEs. Interventions targeting negative affect and social isolation might be beneficial in people with PLEs.

Language in interaction: turn-taking patterns in conversations involving individuals with schizophrenia.

Individuals with schizophrenia generally show difficulties in interpersonal communication. Linguistic analyses shed new light on speech atypicalities in schizophrenia. However, very little is known about conversational interaction management by these individuals. Moreover, the relationship between linguistic features, psychopathology, and patients' subjectivity has received limited attention to date. We used a novel methodology to explore dyadic conversations involving 58 participants (29 individuals with schizophrenia and 29 control persons) and medical doctors. High-quality stereo recordings were obtained and used to quantify turn-taking patterns. We investigated psychopathological dimensions and subjective experiences using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Examination of Anomalous Self Experience scale (EASE), the Autism Rating Scale (ARS) and the Abnormal Bodily Phenomena questionnaire (ABPq). Different turn-taking patterns of both patients and interviewers characterised conversations involving individuals with schizophrenia. We observed higher levels of overlap and mutual silence in dialogues with the patients compared to dialogues with control persons. Mutual silence was associated with negative symptom severity; no dialogical feature was correlated with anomalous subjective experiences. Our findings suggest that individuals with schizophrenia display peculiar turn-taking behaviour, thereby enhancing our understanding of interactional coordination in schizophrenia.

Patient's Experiences of a Cognitive Behaviour Therapy Informed Crisis Intervention for Psychosis Delivered in Inpatient Settings: A Qualitative Exploration.

Cognitive behaviour therapy for psychosis (CBTp) should be offered to patients receiving psychiatric inpatient care, yet very little is known about patients' perspectives on this. The aim of this study was to examine patients' experiences of a CBTp-informed intervention delivered in inpatient settings. We recruited 10 participants from the intervention arm of a randomised controlled trial examining the feasibility and acceptability of a CBTp-informed intervention for psychiatric inpatient settings. We undertook semistructured interviews examining their experiences of the intervention and analysed them using thematic analysis. The study was conducted in partnership with a coproduction group of key stakeholders (people with lived experience, family and carers, and clinicians). The intervention was found helpful by almost all participants, and all participants would recommend it to others in similar situations to themselves. The results demonstrated that participants valued the therapist's professionalism and emphasised the importance of the therapeutic relationship. Participants highlighted the importance of the therapy focusing on navigating admission and developing skills to manage the crisis experience so they could return to their normal lives. Participants described challenges to having psychological therapy in the acute crisis context including therapy interruptions and ongoing distressing experiences of psychosis. The study demonstrated the importance of prioritising the therapeutic relationship, that therapy was a valued process to navigate admission and discharge, but that some environmental and patient-level challenges were present. Further research is needed to explore inpatients' experiences of psychological interventions in this setting. TRIAL REGISTRATION: ISRCTN trial registry: ISRCTN59055607.

Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study.

PURPOSE: Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. METHODS: A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. RESULTS: The total scores on the measures of cognition and social exclusion were strongly associated (ß = - .469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). CONCLUSION: The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders.

Operational Mechanisms of Peer Support Groups and Support for Caregivers of People Living with Serious Mental Illness.

The challenges faced by caregivers of people living with serious mental illness in Canada are well documented in the literature including emotional distress, financial strain, social isolation, and concerns about their physical health following the impact of caregiving. Peer support programs (including peer support groups) emerged as a promising method to attempt to address these challenges. While there is evidence on the positive impacts of peer support groups in providing support for caregivers, the mechanisms by which peer support groups operate and influence support for caregivers of people living with serious mental illness are less understood. This qualitative study took on a co-designed participatory research approach. Fifteen adult caregivers of people living with serious mental illness across Canada were engaged through key informant interviews that lasted for 45 - 60 min each. A thematic analysis was carried out to help understand the operational mechanisms of peer support groups in influencing support for caregivers. The key informant interviews allowed for the identification and description of the following operational mechanisms that influenced the support caregivers received from peer support groups: (1) Group dynamics; (2) Messaging/content; (3) Equity and inclusion, (4) Group philosophy; and (5) Privacy concerns. Findings from this study showed that caregivers identified a number of operational mechanisms of peer support groups that explained how they felt supported when they participated in peer support groups. Among other operational mechanisms, group dynamics in terms of the gathering of caregivers of different age brackets and varying caregiving experience negatively influenced the peer support experience of caregivers. This pointed to the need for group dynamics that consider close age ranges and similar caregiving experience during group meetings to enhance support for caregivers. Caregivers also identified a gap in equity and inclusion in peer support groups that could have otherwise enriched their experience and enhanced the support they looked to receive from the group. Practical examples to enhance equity and inclusion include promoting active listening, using inclusive language, encouraging diverse representation and asking for feedback from peer support group members. While peer support groups in Canada exist independently of one another, it may help to consolidate evidence-based recommendations in the operational mechanisms of these groups, for the benefit of caregivers who turn to these groups for support, having been left on their own by an otherwise fractured mental health system.

"My sister wants to kill me": A case report and systematic review of literature of co-occurring multiple sclerosis and psychosis.

Background: Multiple sclerosis (MS) is a neurological disorder with demyelination of neuronal matter, especially of white matter, with multiple episodes occurring temporally. It has been associated with multiple neurological and psychiatric sequelae. Depression and other affective symptoms are commonly associated with MS. Previous research has also suggested that psychotic symptoms may co-occur with MS as well. Material and Methods: A case report was prepared on the patient admitted to the inpatient unit. Subsequently, a systematic literature review of literature was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model on three databases. Search terms included (MS OR multiple sclerosis) AND (Psychosis OR schizophrenia OR schizoaffective disorder OR psychotic OR hallucination OR delusion). Results: The literature review led to an initial discovery of 2711 hits on PubMed, 1276 hits on PsycINFO, and 5429 hits on Embase. Some patients were diagnosed with MS at an earlier age with a later onset of psychosis, while some were initially diagnosed with psychosis (or schizophrenia) first and subsequently with MS. Psychotic symptoms observed included persecutory delusions, lack of insight, delusions of reference, auditory hallucinations, grandiose delusions, and passivity. The commonly prescribed antipsychotics included risperidone, olanzapine, quetiapine, and aripiprazole. The presence of co-occurring psychosis in MS patients underscores the need for a comprehensive evaluation of symptoms. Conclusion: This case highlights the importance of conducting a magnetic resonance imaging (MRI) brain not only for initial onset psychosis but also for any sudden changes in patients who have had a relatively stable course. Moreover, psychosis can affect treatment adherence in MS, making it all the more critical to identify and manage it promptly.