Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): Protocol paper.

BACKGROUND: Global evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery. METHODS: The setting is sub-cities of Addis Ababa and rural districts in south-central Ethiopia covering 1.1 million people and including rural, urban and homeless populations. SCOPE comprises (1) formative work to understand care pathways and community resources (resource mapping); examine family context and communication (ethnography); develop valid measures of family communication and personal recovery; and establish platforms for community engagement and involvement of people with lived experience; (2a) a population-based incidence study, (2b) a case-control study and (2c) a cohort study with 12 months follow-up involving 440 people with psychosis (390 rural/Addis Ababa; 50 who are homeless), 390 relatives and 390 controls. We will test hypotheses about incidence rates in rural vs. urban populations and men vs. women; potential aetiological role of khat (a commonly chewed plant with amphetamine-like properties) and traumatic exposures in psychosis; determine profiles of needs at first contact and predictors of outcome; (3) participatory workshops to develop programme theory and inform co-development of interventions, and (4) evaluation of the impact of early identification strategies on engagement with care (interrupted time series study). Findings will inform development of (5) a protocol for (5a) a feasibility cluster randomised controlled trial of interventions for people with recent-onset psychosis in rural settings and (5b) two uncontrolled pilot studies to test acceptability, feasibility of co-developed interventions in urban and homeless populations.

Sociodemographic and clinical correlates of hallucinations in patients entering an early intervention program for first episode psychosis.

Hallucinations are a core feature of psychosis, and their severity during the acute phase of illness is associated with a range of poor outcomes. Various clinical and sociodemographic factors may predict hallucinations and other positive psychotic symptoms in first episode psychosis (FEP). Despite this, the precise factors associated with hallucinations at first presentation to an early intervention service have not been extensively researched. Through detailed interviews and chart reviews, we investigated sociodemographic and clinical predictors in 636 minimally-medicated patients who entered PEPP-Montréal, an early intervention service for FEP, between 2003 and 2018. Hallucinations were measured using the Scale for the Assessment of Positive Symptoms (SAPS), while negative symptoms were assessed using the Scale for the Assessment of Negative symptoms (SANS). Depressive symptoms were evaluated through the Calgary Depression Scale for Schizophrenia (CDSS), and anxiety symptoms via the Hamilton Rating Scale for Anxiety (HAS). A majority (n = 381, 59.9 %) of the sample presented with clinically significant hallucinations (SAPS global hallucinations score ≥ 3) at program entry. These patients had an earlier age at onset, fewer years of education, and a higher severity of delusions, depression and negative symptoms than those without clinical-level hallucinations. These results suggest that individuals with clinically significant hallucinations at admission tend to be younger and have a greater overall symptom burden. This makes it especially important to monitor hallucinations alongside delusions, depression and negative symptoms in order to identify who might benefit from targeted interventions. The implications of these findings for early intervention and person-centered care are discussed.

Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables. We sampled data from two cross-sectional datasets of first- and multi-episode psychosis, resulting in a sample of 163 patients and 119 non-clinical controls. To address our proposed disease progression model and evaluate potential heterogeneity, we applied a machine-learning algorithm, SuStaIn, to the patient data. SuStaIn uniquely integrates clustering and disease progression modeling and identified three patient subtypes. Subtype 0 showed normal-range performance on all variables. In comparison, Subtype 1 showed lower episodic memory, social cognition, functional outcome, and higher negative symptoms, while Subtype 2 showed lower hippocampal-cortical connectivity and episodic memory. Subtype 1 deteriorated from episodic memory to social cognition, negative symptoms, functional outcome to bilateral hippocampal-cortical dysconnectivity, while Subtype 2 deteriorated from bilateral hippocampal-cortical dysconnectivity to episodic memory and social cognition, functional outcome to negative symptoms. This first application of SuStaIn in a multiscale psychiatric model provides distinct disease trajectories of hippocampal-cortical connectivity, which might underlie the heterogeneous behavioral manifestations of psychosis.

Patient-reported outcome measures in early psychosis: A cross-cultural, longitudinal examination of the self-reported health and self-reported mental health measures in Chennai, India and Montreal, Canada.

OBJECTIVE: Despite their acknowledged value, patient-reported outcome measures (PROMs) are infrequently used in psychosis, particularly in low-and middle-income countries. We compared ratings on two single-item PROMs, Self-Rated Health (SRH) and Self-Rated Mental Health (SRMH), of persons receiving similar early psychosis services in Chennai, India and Montreal, Canada. We hypothesized greater improvements in SRH and SRMH in the Chennai (compared to the Montreal) sample. METHODS: Participants (Chennai N = 159/168 who participated in the larger study; Montreal N = 74/165 who participated in the larger study) completed the SRH and SRMH during at least two out of three timepoints (entry, months 12 and 24). Repeated measures proportional odds logistic regressions examined the effects of time (baseline to month 24), site, and relevant baseline (e.g., gender) and time-varying covariates (i.e., symptoms) on SRH and SRMH scores. RESULTS: SRH (but not SRMH) scores significantly differed between the sites at baseline, with Chennai patients reporting poorer health (OR: 0.33; CI: 0.18, 0.63). While Chennai patients reported similar significant improvements in their SRH (OR: 7.03; CI: 3.13; 15.78) and SRMH (OR: 2.29, CI: 1.03, 5.11) over time, Montreal patients only reported significant improvements in their SRMH. Women in Chennai (but not Montreal) reported lower mental health than men. Higher anxiety and longer durations of untreated psychosis were associated with poorer SRH and SRMH, while negative symptoms were associated with SRH. CONCLUSIONS: As hypothesized, Chennai patients reported greater improvements in health and mental health. The marked differences between health and mental health in Montreal, in contrast to the overlap between the two in Chennai, aligns with previous findings of clearer distinctions between mind and body in Western societies. Cross-context (e.g., anxiety) and context-specific (e.g., gender) factors influence patients' health perceptions. Our results highlight the value of integrating simple PROMs in early psychosis.

Similar and different? A cross-cultural comparison of the prevalence, course of and factors associated with suicidal thoughts and behaviors in first-episode psychosis in Chennai, India and Montreal, Canada.

BACKGROUND: Data from high-income countries (HICs) show a high risk of suicidal thoughts and behaviors (STBs) in first-episode psychosis (FEP). It is unknown, however, whether rates and associated factors differ in low- and middle-income countries (LMICs). AIMS: We therefore aimed to compare the 2-year course of STBs and associated factors in persons with FEP treated in two similarly structured early intervention services in Chennai, India and Montreal, Canada. METHOD: To ensure fit to the data that included persons without STBs and with varying STBs' severity, a hurdle model was conducted by site, including known predictors of STBs. The 2-year evolution of STBs was compared by site with mixed-effects ordered logistic regression. RESULTS: The study included 333 FEP patients (168 in Chennai, 165 in Montreal). A significant decrease in STBs was observed at both sites (OR = 0.87; 95% CI [0.84, 0.90]), with the greatest decline in the first 2 months of follow-up. Although three Chennai women died by suicide in the first 4 months (none in Montreal), Chennai patients had a lower risk of STBs over follow-up (OR = 0.44; 95% CI [0.23, 0.81]). Some factors (depression, history of suicide attempts) were consistently associated with STBs across contexts, while others (gender, history of suicidal ideation, relationship status) were associated at only one of the two sites. CONCLUSIONS: This is the first study to compare STBs in FEP between two distinct geo-sociocultural contexts (an HIC and an LMIC). At both sites, STBs reduced after treatment initiation, suggesting that early intervention reduces STBs across contexts. At both sites, for some patients, STBs persisted or first appeared during follow-up, indicating need for suicide prevention throughout follow-up. Our study demonstrates contextual variations in rates and factors associated with STBs. This has implications for tailoring suicide prevention and makes the case for more research on STBs in FEP in diverse contexts.

Patient-reported outcome measures in early psychosis: Evaluating the psychometric properties of the single-item self-reported health and self-reported mental health measures in Chennai, India and Montreal, Canada.

AIM: Patient-reported outcome measures (PROMs) provide valuable information and promote shared decision-making but are infrequently used in psychosis. Self-rated Health (SRH) and Self-rated Mental Health (SRMH) are single-item PROMs in which respondents rate their health and mental health from 'poor' to 'excellent'. We examined the psychometric properties of the SRH and SRMH in early psychosis services in Chennai, India and Montreal, Canada. METHODS: Assessments were completed in Tamil/English in Chennai and French/English in Montreal. Test-retest reliability included data from 59 patients in Chennai and Montreal. Criterion validity was examined against clinician-rated measures of depression, anxiety, positive and negative symptoms, and a quality-of-life PROM for 261 patients in Chennai and Montreal. RESULTS: SRH and SRMH had good to excellent test-retest reliability (ICC >0.63) at both sites and in English and Tamil (but not French). Results for criterion validity were mixed. In Montreal, low SRH was associated with not being in positive symptom remission, and poorer functioning and quality of life. SRH was associated only with functioning in Chennai. No associations were found for SRMH in Montreal. In Chennai, low SRMH was associated with not being in positive symptom remission and poorer functioning. CONCLUSIONS: Patient-reported outcome measures may perform differently across contexts as a potential function of variations in sociodemographics, illness characteristics/course, understandings of health/mental health, and so forth. More work is needed to understand if discrepancies between PROMs and CROMs indicate poor validity of PROMs or 'valid' differences between patient and clinician perceptions. Our work suggests that single-item PROMs can be feasibly integrated into clinical settings.

Exploring the Relationship Between Suicidality and Persistent Negative Symptoms Following a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups. STUDY DESIGN: In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS). STUDY RESULTS: Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms. CONCLUSION: We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.

Trust of patients and families in mental healthcare providers and institutions: a cross-cultural study in Chennai, India, and Montreal, Canada.

PURPOSE: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada, and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. METHODS: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Nonparametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. RESULTS: The study included 333 patients (Montreal = 165, Chennai = 168) and 324 family members (Montreal = 128, Chennai = 168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. CONCLUSION: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes.

Combinations and Temporal Associations Among Precursor Symptoms Before a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we aimed to investigate combinations and temporal associations among precursor symptoms. STUDY DESIGN: Participants were from PEPP-Montréal, a catchment-based early intervention program for FEP. Through semistructured interviews, collateral from relatives, and a review of health and social records, we retrospectively measured the presence or absence of 29 precursor symptoms, including 9 subthreshold psychotic and 20 nonpsychotic symptoms. Sequences of symptoms were derived from the timing of the first precursor symptom relative to the onset of FEP. STUDY RESULTS: The sample included 390 participants (68% men; age range: 14-35 years). Combinations of precursor symptoms most frequently featured depression, anxiety, and substance use. Of 256 possible pairs of initial and subsequent precursor symptoms, many had asymmetrical associations: eg, when the first symptom was suspiciousness, the incidence rate ratio (IRR) of subsequent anxiety was 3.40 (95% confidence interval [CI]: 1.79, 6.46), but when the first symptom was anxiety, the IRR of subsequent suspiciousness was 1.15 (95% CI: 0.77, 1.73). CONCLUSIONS: A detailed examination of precursor symptoms reveals diverse clinical profiles that cut across diagnostic categories and evolve longitudinally prior to FEP. Their identification may contribute to risk assessments and provide insights into the mechanisms of illness progression.

Sociodemographic and clinical risk factors associated with suicidal ideation and attempt during a 2-year early intervention program for first-episode psychosis.

BACKGROUND: Identifying risk factors for suicidal ideation and attempt among first-episode psychosis patients is essential to prevent suicide in this high-risk population. We investigated risk factors at admission for suicidal ideation and attempt during a 2-year early intervention program. METHODS: Our sample included patients aged 18-35 years who were consecutively admitted to an early intervention program (2003-2017). Sociodemographic and clinical variables were obtained from a longitudinal study, while data on suicidal ideation and attempt were collected via systematic file review. Univariable and multivariable logistic regressions assessed the association of these variables with suicide ideation and attempt. RESULTS: Of 446 participants, 35 (7.8 %) attempted suicide during the 2-year follow up, including two resulting in death (0.45 %), and 168 (37.7 %) reported solely suicidal ideation. Multivariable analyses indicated living alone (OR = 4.01, CI = 2.11-7.63), affective psychosis (OR = 1.95, CI = 1.22-3.14) and depressive symptomatology (OR = 1.45, CI = 1.13-1.86) were associated with increased risk for suicidal ideation. Attempting suicide close to admission (OR = 10.29, CI = 3.63-29.22), living alone (OR = 4.17, CI = 1.40-12.35), and depressive (OR = 1.67, CI = 1.06-2.63) and positive symptomatology (OR = 1.60, CI = 1.02-2.50) were associated with increased risk for suicide attempt. Attempting suicide close to admission (OR = 11.65, CI = 4.08-33.30), being part of an ethnic minority (OR = 3.71, CI = 1.59-8.63), and presenting lower anxiety (OR = 0.58, CI = 0.36-0.94) were the only factors specifically associated with suicide attempt compared to ideation. CONCLUSION: Close monitoring of patients who recently attempted suicide, live alone, are part of an ethnic minority, and present with affective and positive symptomatology may help reduce the risk of suicide-related outcomes during early intervention programs.

Short communication: Prevalence of long-acting injectable antipsychotic use in Canadian early intervention services for psychosis.

The use of long-acting injectable (LAI) antipsychotic drugs for psychotic disorders in Canada has been historically low compared to other jurisdictions despite advantages of LAIs in improving medication adherence and preventing relapse. In response, treatment recommendations were developed in 2013 by the Canadian Consortium for Early Intervention in Psychosis and other Canadian provincial expert groups. The impact of these guidelines needed to be assessed. To document practices in LAI use in early intervention services (EIS) for psychosis, Canadian EIS were surveyed in 2016 (n = 18) and 2020 (n = 12). Trends and descriptive information were examined using repeated cross-sectional survey data. Eight EIS responded to surveys at both time points allowing for longitudinal comparisons. Outcomes of interest included i) LAI use frequency, ii) timing of LAI starts, and iii) factors influencing LAI use. Cross-sectional analysis identified a significant increase in overall LAI usage (24.7% in 2016; 35.1% in 2020). Longitudinal analysis indicated that patients in the second program year saw the greatest increase in LAI use between 2016 and 2020 (25.6% vs. 36.1%), especially among patients under community treatment orders (65.5% vs. 81.5%). Results support increases in LAI use over time, accessibility, awareness, and increasing comfortability among Canadian clinicians.

Subjective quality of life among first-episode psychosis patients in Chennai, India and Montreal, Canada.

Differences in subjective quality of life among persons receiving early intervention for psychosis in varying geo-sociocultural contexts have rarely been examined. Our prospective longitudinal study compared the quality of life of persons with first-episode psychosis receiving two years of similar early intervention in Chennai, India and Montreal, Canada. We hypothesized that general life satisfaction would be higher in Chennai compared to Montreal, and that social relations (a specific quality of life component) would also be higher in Chennai and positively contribute to general life satisfaction. Participants completed the general satisfaction and social relations domains of the Wisconsin Quality of Life Index at baseline, months 12 and 24. Baseline weighted mean general satisfaction and social relations scores were in the low to moderate range. Generalized estimating equation analyses showed that general satisfaction scores increased with time [Wald χ2 (1) = 125.28, p < 0.001] and were higher in Chennai than in Montreal [Wald χ2 (1) = 7.50, p = 0.006]. Social relations scores showed the highest association with general satisfaction scores (B = 0.52), followed by positive symptom remission (B = 0.24) and gender (B = 0.18) with Chennai males having the highest general satisfaction scores. Social relations weighted mean scores increased with time [Wald χ2 (1) = 87.30, p < 0.001] and were positively associated with years of education [Wald χ2 (1) = 4.76, p = 0.029] and early negative symptom remission [Wald χ2 (1) = 7.38, p = 0.007]. Our results suggest that subjective quality of life may improve following early intervention for psychosis across contexts. Our findings advance knowledge about the role of sociocultural (e.g., gender) and clinical factors in influencing subjective outcomes in psychosis, and point to social support networks and symptom remission as avenues to boost quality of life.

Effects of Anticholinergic Burden on Verbal Memory Performance in First-Episode Psychosis.

OBJECTIVES: Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients' verbal memory performance would improve but would remain inferior to controls. METHODS: Patients (n = 311; low anticholinergic burden [n = 241] and high anticholinergic burden [n = 70], defined by a Drug Burden Index cut-off of 1) and healthy controls (n = 128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at months 3 and 12. RESULTS: Cross-sectionally, using an analysis of variance, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3, F(2,430) = 52.33, P < 0.001. Longitudinally, using a Generalized Estimating Equation model, the verbal memory performance of all groups improved over time. However, patients' performance overall remained poorer than the controls. CONCLUSION: These findings highlight the importance of considering the anticholinergic burden when prescribing medications in the early stages of the disease.

Return on investment from service transformation for young people experiencing mental health problems: Approach to economic evaluations in ACCESS Open Minds (Esprits ouverts), a multi-site pan-Canadian youth mental health project.

Introduction: Mental health problems are common globally, and typically have their onset in adolescence and early adulthood-making youth (aged 11-25) an optimal target for prevention and early intervention efforts. While increasing numbers of youth mental health (YMH) initiatives are now underway, thus far few have been subject to economic evaluations. Here we describe an approach to determining the return on investment of YMH service transformation via the pan-Canadian ACCESS Open Minds (AOM) project, for which a key focus is on improving access to mental health care and reducing unmet need in community settings. Approach: As a complex intervention package, it is hoped that the AOM transformation will: (i) enable early intervention through accessible, community-based services; (ii) shift care away toward these primary/community settings and away from acute hospital and emergency services; and (iii) offset at least some of the increased costs of primary care/community-based mental health services with reductions in the volume of more resource-intensive acute, emergency, hospital or specialist services utilized. Co-designed with three diverse sites that represent different Canadian contexts, a return on investment analysis will (separately at each site) compare the costs generated by the intervention, including volumes and expenditures associated with the AOM service transformation and any contemporaneous changes in acute, emergency, hospital or service utilization (vs. historical or parallel comparators). Available data from health system partners are being mobilized to assess these hypotheses. Anticipated results: Across urban, semi-urban and Indigenous sites, the additional costs of the AOM transformation and its implementation in community settings are expected to be at least partially offset by a reduction in the need for acute, emergency, hospital or specialist care. Discussion: Complex interventions such as AOM aim to shift care "upstream": away from acute, emergency, hospital and specialist services and toward community-based programming which is more easily accessible, often more appropriate for early-stage presentations, and more resource-efficient. Carrying out economic evaluations of such interventions is challenging given the constraints of available data and health system organization. Nonetheless, such analyses can advance knowledge, strengthen stakeholder engagement, and further implementation of this public health priority.

Using dimensionality-reduction techniques to understand the organization of psychotic symptoms in persistent psychotic illness and first episode psychosis.

Psychotic disorders are highly heterogeneous. Understanding relationships between symptoms will be relevant to their underlying pathophysiology. We apply dimensionality-reduction methods across two unique samples to characterize the patterns of symptom organization. We analyzed publicly-available data from 153 participants diagnosed with schizophrenia or schizoaffective disorder (fBIRN Data Repository and the Consortium for Neuropsychiatric Phenomics), as well as 636 first-episode psychosis (FEP) participants from the Prevention and Early Intervention Program for Psychosis (PEPP-Montreal). In all participants, the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS) were collected. Multidimensional scaling (MDS) combined with cluster analysis was applied to SAPS and SANS scores across these two groups of participants. MDS revealed relationships between items of SAPS and SANS. Our application of cluster analysis to these results identified: 1 cluster of disorganization symptoms, 2 clusters of hallucinations/delusions, and 2 SANS clusters (asocial and apathy, speech and affect). Those reality distortion items which were furthest from auditory hallucinations had very weak to no relationship with hallucination severity. Despite being at an earlier stage of illness, symptoms in FEP presentations were similarly organized. While hallucinations and delusions commonly co-occur, we found that their specific themes and content sometimes travel together and sometimes do not. This has important implications, not only for treatment, but also for research-particularly efforts to understand the neurocomputational and pathophysiological mechanism underlying delusions and hallucinations.

Differential Trajectories of Delusional Content and Severity Over 2 Years of Early Intervention for Psychosis: Comparison Between Chennai, India, and Montréal, Canada.

BACKGROUND: There exist few direct studies of delusional content in psychosis across geo-cultural contexts, especially those in which treatment protocols and measures are comparable. To directly examine an illness outcome that is potentially culturally mediated, this study investigated the baseline presentation and longitudinal trajectory of delusions in first-episode psychosis (FEP) across 2 similar treatment settings in Montréal (Canada) and Chennai (India). STUDY DESIGN: Patients entering an early intervention program for FEP in Chennai (N = 168) and Montréal (N = 165) were compared on site-level differences in the presentation of delusions across specific time points over 2 years of treatment. Delusions were measured using the Scale for Assessment of Positive Symptoms. Chi-square and regression analyses were conducted. STUDY RESULTS: At baseline, delusions were more frequent in Montréal than in Chennai (93% vs 80%, respectively; X2(1) = 12.36, P < .001). Thematically, delusions of grandiosity, religiosity, and mind reading were more common in Montréal than in Chennai (all P < .001); however, these baseline differences did not persist over time. Regression revealed a significant time-by-site interaction in the longitudinal course of delusions, which differs from the trajectory of other FEP-positive symptom domains. CONCLUSIONS: To the best of our knowledge, this is the first direct comparison of delusions in similar programs for FEP across 2 different geo-cultural contexts. Our findings support the notion that delusion themes follow consistent ordinal patterns across continents. Future work is needed to unpack the differences in severity that present at baseline and minor differences in content.

Context and Expectations Matter: Social, Recreational, and Independent Functioning among Youth with Psychosis in Chennai, India and Montreal, Canada.

OBJECTIVES: Most cross-cultural psychosis research has focused on a limited number of outcomes (generally symptom-related) and perspectives (often clinician-/observer-rated). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to patient-reported measures of social, recreational, and independent functioning. Addressing this gap, this study aimed to compare these outcomes in first-episode psychosis at a high-income site and a lower middle-income site. METHODS: Patients receiving similarly designed early intervention for psychosis in Chennai, India (N = 164) and Montreal, Canada (N = 140) completed the self-reported Social Functioning Scale-Early Intervention, which measures prosocial, recreation, and independence-performance functioning. Their case managers rated expected independence-performance functioning. Both sets of assessments were done at entry and Months 6, 18, and 24. Linear mixed model analyses of differences between sites and over time were conducted, accounting for other pertinent variables, especially negative symptoms. RESULTS: Linear mixed models showed that prosocial, recreation, and independence-performance functioning scores were significantly higher in Montreal than Chennai and did not change over time. Expected independence-performance was also higher in Montreal and increased over time. Negative symptoms and education independently predicted prosocial, recreation, and expected independence-performance functioning. When added to the model, expected independence-performance predicted actual independence-performance and site was no longer significant. At both sites, prosocial and recreation scores were consistently lower (<40%) than independence-performance (40-65%). CONCLUSION: This is the first cross-cultural investigation of prosocial, recreation, and independent functioning in early psychosis. It demonstrates that these outcomes differ by socio-cultural context. Differing levels of expectations about patients, themselves shaped by cultural, illness, and social determinants, may contribute to cross-cultural variations in functional outcomes. At both sites, social, recreational, and independent functioning were in the low-to-moderate range and there was no improvement over time, underscoring the need for effective interventions specifically designed to impact these outcomes.

Trust of patients and families in mental healthcare providers and institutions: A cross-cultural study in Chennai, India and Montreal, Canada.

Purpose: Cross-cultural psychosis research has typically focused on a limited number of outcomes (generally symptom-related). It is unknown if the purported superior outcomes for psychosis in some low- and middle-income countries extend to fundamental treatment processes like trust. Addressing this gap, we studied two similar first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized higher trust in healthcare institutions and providers among patients and families in Chennai at baseline and over follow-up. Methods: Upon treatment entry and at months 3, 12 and 24, trust in healthcare providers was measured using the Wake Forest Trust scale and trust in the healthcare and mental healthcare systems using two single items. Non-parametric tests were performed to compare trust levels across sites and mixed-effects linear regression models to investigate predictors of trust in healthcare providers. Results: The study included 333 patients (Montreal=165, Chennai=168) and 324 family members (Montreal=128, Chennai=168). Across all timepoints, Chennai patients and families had higher trust in healthcare providers and the healthcare and mental healthcare systems. The effect of site on trust in healthcare providers was significant after controlling for sociodemographic characteristics known to impact trust. Patients' trust in doctors increased over follow-up. Conclusion: This study uniquely focuses on trust as an outcome in psychosis, via a comparative longitudinal analysis of different trust dimensions and predictors, across two geographical settings. The consistent differences in trust levels between sites may be attributable to local cultural values and institutional structures and processes and underpin cross-cultural variations in treatment engagement and outcomes.

Examining the psychobiological response to acute social stress across clinical stages and symptom trajectories in the early psychosis continuum.

The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis - and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.