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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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 χ 2 (1) = 125.28, p < 0.001] and were higher in Chennai than in Montreal [Wald χ 2 (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 χ 2 (1) = 87.30, p < 0.001] and were positively associated with years of education [Wald χ 2 (1) = 4.76, p = 0.029] and early negative symptom remission [Wald χ 2 (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., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest in to the submitted work. Unrelated to this manuscript, in the last three years, Dr. Margolese reports grants from Aifred, SyneuRx and the Montreal General Hospital Foundation; and served as speaker and/or member of an advisory board committee for AbbVie, HLS, Janssen, Lundbeck, Otsuka, Teva and Sunovion. All other authors declare no conflicts of interest. Unrelated to this manuscript and prior to the past three years, Dr. Joober served as speaker and member of advisory board committees for Pfizer, Janssen, BMS, Sunovian, Myelin, Otsuka, Lundbeck, Shire and Perdue, and received grants from Janssen, BMS, Otsuka, Lundbeck, Astra Zeneca and HLS., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diagnostic criteria used in autism research have undergone a shift towards the inclusion of a larger population, paralleled by increasing, but variable, estimates of autism prevalence across clinical settings and continents. A categorical diagnosis of autism spectrum disorder is now consistent with large variations in language, intelligence, comorbidity, and severity, leading to a heterogeneous sample of individuals, increasingly distant from the initial prototypical descriptions. We review the history of autism diagnosis and subtyping, and the evidence of heterogeneity in autism at the cognitive, neurological, and genetic levels. We describe two strategies to address the problem of heterogeneity: clustering, and truncated-compartmentalized enrollment strategy based on prototype recognition. The advances made using clustering methods have been modest. We present an alternative, new strategy for dissecting autism heterogeneity, emphasizing incorporation of prototypical samples in research cohorts, comparison of subgroups defined by specific ranges of values for the clinical specifiers, and retesting the generality of neurobiological results considered to be acquired from the entire autism spectrum on prototypical cohorts defined by narrow specifiers values., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Social anxiety (SA), a prevalent comorbid condition in psychotic disorders with a negative impact on functioning, requires adequate intervention relatively early. Using a randomized controlled trial, we tested the efficacy of a group cognitive-behavioral therapy intervention for SA (CBT-SA) that we developed for youth who experienced the first episode of psychosis (FEP). For our primary outcome, we hypothesized that compared to the active control of group cognitive remediation (CR), the CBT-SA group would show a reduction in SA that would be maintained at 3- and 6-month follow-ups. For secondary outcomes, it was hypothesized that the CBT-SA group would show a reduction of positive and negative symptoms and improvements in recovery and functioning., Method: Ninety-six patients with an FEP and SA, recruited from five different FEP programs in the Montreal area, were randomized to 13 weekly group sessions of either CBT-SA or CR intervention., Results: Linear mixed models revealed that multiple measures of SA significantly reduced over time, but with no significant group differences. Positive and negative symptoms, as well as functioning improved over time, with negative symptoms and functioning exhibiting a greater reduction in the CBT-SA group., Conclusions: While SA decreased over time with both interventions, a positive effect of the CBT-SA intervention on measures of negative symptoms, functioning, and self-reported recovery at follow-up suggests that our intervention had a positive effect that extended beyond symptoms specific to SA.ClinicalTrials.gov identifier: NCT02294409.

Language is an important aspect of communication and language status is known to impact healthcare accessibility, its perceived suitability, and outcomes. However, its influence on treatment engagement and/or disengagement is unknown. Our study therefore sought to investigate the impact of language on service disengagement in an early intervention psychosis program in Montreal, Quebec (a province with French as the official language). We aimed to compare service disengagement between a linguistic minority group (i.e., English) vis-à-vis those whose preferred language was French and to explore the role of language in service engagement. Using a mixed methods sequential design, we tested preferred language and several sociodemographic characteristics associated with service disengagement in a time-to-event analysis with Cox proportional hazards regression models ( N  = 338). We then conducted two focus groups with English (seven patients) and French speakers (five patients) to further explore differences between the two linguistic groups. Overall, 24% ( n  = 82) disengaged from the service before the two-year mark. Those whose preferred language was English were more likely to disengage ( n  = 47, 31.5%) than those whose preferred language was French ( n  = 35, 18.5%; χ2 = 9.11, p  < .01). This remained significant in the multivariate regression. In focus groups, participants identified language as one aspect of a complex communication process between patients and clinicians and highlighted the importance of culture in the clinical encounter. Language status of patients plays an important role in their engagement with early psychosis services. Our findings underscore the value of establishing communication and cultural understanding in creating clinical/therapeutic alliance.

Competing Interests: Competing interests: Christina Rigas is supported by a CGS-CIHR Master’s Award. Mona Ben m’rad has received honoraria from the Régie de l’assurance maladie du Québec; speaker fees and consulting fees from Otsuka; speaker fees from GSK; and equipment, materials, gifts or “other” from Amgen and Otsuka. She has also received consulting fees from Creative Research Design and has contributed to the e-learning platform Nephrons and Neurons, which is funded by Otsuka. She serves as an unpaid consultant to Health Canada on the advisory board on renal adverse effects of COVID-19 immunization. Harmehr Sekhon is supported by postdoctoral fellowship awards from CIHR, Mitacs and AGE-WELL. Soham Rej receives salary support from a Fonds de Recherche Quebec – Santé (FRQS) clinician-scientist salary award, has received operating grants from Mitacs, is on a steering committee for AbbVie, and has shares in Aifred Health. No other competing interests were declared.

Horyzons is a digital health intervention designed to support recovery in young people receiving specialized early intervention services for first-episode psychosis (FEP). Horyzons was developed in Australia and adapted for implementation in Canada based on input from clinicians and patients (Horyzons-Canada Phase 1) and subsequently pilot-tested with 20 young people with FEP (Horyzons-Canada Phase 2)., Objective: To understand the experiences of young adults with FEP who participated in the pilot study based on focus group data., Methods: Among the twenty individuals that accessed the intervention, nine participated across four focus groups. Three team members were involved in data management and analysis, informed by a thematic analysis approach. A coding framework was created by adapting the Phase 1 framework to current study objectives, then revised iteratively by applying it to the current data. Once the coding framework was finalized, it was systematically applied to the entire dataset., Results: Four themes were identified: (1) Perceiving Horyzons-Canada as helpful for recovery; (2) Appreciating core intervention components (i.e., peer networking; therapeutic content; moderation) and ease of use; (3) Being unaware of its features; and (4) Expressing concerns, suggestions, and future directions., Conclusions: Horyzons-Canada was well received, with participants wanting it to grow in scale, accessibility, and functionality.

Digital health innovations may help to improve access to psychosocial therapy and peer support; however, the existence of evidence-based digital health interventions for individuals recovering from a first-episode psychosis (FEP) remains limited. This study aims to investigate the feasibility, acceptability, safety, and pre-post outcomes of Horyzons-Canada (HoryzonsCa), a Canadian adaptation of a digital mental health intervention consisting of psychosocial interventions, online social networking, and clinical and peer support moderation. Using a convergent mixed-methods research design, we recruited participants from a specialized early intervention clinic for FEP in Montreal, Canada. Twenty-three participants (mean age = 26.8) completed baseline assessments, and 20 completed follow-up assessments after 8 weeks of intervention access. Most participants provided positive feedback on general experience (85%, 17/20) and the utility of Horyzons for identifying their strengths (70%, 14/20). Almost all perceived the platform as easy to use (95%, 19/20) and felt safe using it (90%, 18/20). There were no adverse events related to the intervention. Participants used HoryzonsCa to learn about their illness and how to get better (65%, 13/20), receive support (60%, 12/20), and access social networking (35%, 7/20) and peer support (30%, 6/20). Regarding adoption, 65% (13/20) logged in at least 4 times over 8 weeks. There was a nonsignificant increase in social functioning and no deterioration on the Clinical Global Impression Scale. Overall, HoryzonsCa was feasible to implement and perceived as safe and acceptable. More research is needed with larger sample sizes and using in-depth qualitative methods to better understand the implementation and impact of HoryzonsCa., (© 2023. The Author(s).)

Background: Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression., Methods: Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions., Results: After Bonferroni correction, having a subthreshold psychotic ( v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94-2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10-3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38-4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55-7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01-0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset., Conclusions: Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.

Introduction: Although extensively studied in high-income countries (HICs) and less so in low- and middle-income countries (LMICs), pathways to care and treatment delays in early psychosis have not been compared across contexts. We compared pathways to early intervention for psychosis in an HIC (Montreal, Canada) and an LMIC (Chennai, India). We hypothesised that the duration of untreated psychosis (DUP) would be longer in Chennai., Methods: The number of contacts preceding early intervention, referral sources, first contacts, and DUP and its referral and help-seeking components of first-episode psychosis patients at both sites were similarly measured and compared using chi-square analyses and t tests/one-way ANOVAs., Results: Overall and help-seeking DUPs of Chennai (N = 168) and Montreal (N = 165) participants were not significantly different. However, Chennai patients had shorter referral DUPs [mean = 12.0 ± 34.1 weeks vs. Montreal mean = 13.2 ± 28.7 weeks; t(302.57) = 4.40; p < 0.001] as the early intervention service was the first contact for 44% of them (vs. 5% in Montreal). Faith healers comprised 25% of first contacts in Chennai. Those seeing faith healers had significantly shorter help-seeking but longer referral DUPs. As predicted, most (93%) Montreal referrals came from medical sources. Those seeing psychologists/counsellors/social workers as their first contact had longer DUPs., Conclusion: Differences in cultural views about mental illnesses and organizational structures shape pathways to care and their associations with treatment delays across contexts. Both formal and informal sources need to be targeted to reduce delays. Early intervention services being the first portal where help is sought can reduce DUP especially if accessed early on in the illness course., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© 2023. The Author(s).)

Objectives: Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion., Methods: We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED., Results: Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups ( Q  < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3 , CSGALNACT1, NEGR1 , NR1H3 ) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation., Conclusions: Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology.

Aim: Childhood trauma increases social functioning deficits in first-episode psychosis (FEP) and is negatively associated with higher-order social cognitive processes such as emotion recognition (ER). We investigated the relationship between childhood trauma severity and ER capacity, and explored sex as a potential factor given sex differences in childhood trauma exposure., Methods: Eighty-three FEP participants (52 males, 31 females) and 69 nonclinical controls (49 males, 20 females) completed the CogState Research Battery. FEP participants completed the Childhood Trauma Questionnaire. A sex × group (FEP, controls) ANOVA examined ER differences and was followed by two-way ANCOVAs investigating sex and childhood trauma severity (none, low, moderate, and severe) on ER and global cognition in FEP., Results: FEP participants had significantly lower ER scores than controls (p = .035). No significant sex × group interaction emerged for ER F(3, 147) = .496, p = .438 [95% CI = -1.20-0.57], partial η 2  = .003. When controlling for age at psychosis onset, a significant interaction emerged in FEP between sex and childhood trauma severity F(3, 71) = 3.173, p = .029, partial η 2  = .118. Males (n = 9) with severe trauma showed ER deficits compared to females (n = 8) (p = .011 [95% CI = -2.90 to -0.39]). No significant interaction was observed for global cognition F(3, 69) = 2.410, p = .074, partial η 2  = .095., Conclusions: These preliminary findings provide support for longitudinal investigations examining whether trauma severity differentially impacts ER in males and females with FEP., (© 2022 John Wiley & Sons Australia, Ltd.)

Across subthreshold psychotic and nonpsychotic syndromes, symptoms experienced before the onset of a first episode of psychosis (FEP) may index distinct illness trajectories. We aimed to examine the associations between three types of pre-onset symptoms (self-harm, suicide attempts, and subthreshold psychotic) and outcome trajectories during FEP. Participants with FEP were recruited from PEPP-Montreal, a catchment-based early intervention service. Pre-onset symptoms were systematically assessed through interviews with participants (and their relatives) and reviews of health and social records. Over 2 years of follow-up at PEPP-Montreal, 3-8 repeated measures were collected for positive, negative, depressive, and anxiety symptoms, as well as functioning. We applied linear mixed models to examine associations between pre-onset symptoms and outcome trajectories. We found that on average over follow-up, participants with pre-onset self-harm had more severe positive, depressive, and anxiety symptoms compared with other participants (standardized mean differences: 0.32-0.76), while differences in negative symptoms and functioning were not significant. Associations did not differ by gender and remained similar after adjusting for the duration of untreated psychosis, substance use disorder, or baseline diagnosis of affective psychosis. Over time, depressive and anxiety symptoms improved among individuals with pre-onset self-harm, such that they converged with other individuals by the end of the follow-up. Similarly, pre-onset suicide attempts were associated with elevated depressive symptoms that improved over time. Pre-onset subthreshold psychotic symptoms were not associated with outcomes, except for a slightly different trajectory of functioning. Individuals with pre-onset self-harm or suicide attempts may benefit from early interventions that target their transsyndromic trajectories. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Competing Interests: Competing interests: R. Joober served as speaker and member of advisory board committees for Pfizer, Janssen, BMS, Sunovian, Myelin, Otsuka, Lundbeck, shire and Perdue. He also received grants from Janssen, BMS, Otsuka, Lundbeck, Astra Zeneca and HLS. P. Sabesan has received speaker fees from Lundbeck Canada. L. Palaniyappan is co-editor in chief of the Journal of Psychiatry and Neuroscience but was not involved in the review of or decision to accept the manuscript for publication. He has received personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited UK, and the Canadian Psychiatric Association; book royalties from Oxford University Press; and investigator- initiated educational grants from Sunovion, Janssen Canada, and Otsuka Canada. All of these are unrelated to the present work. No other competing interests were declared.

Purpose: While the prevalence of delusional themes appears to be consistent across geographic contexts, little is known about the relative prevalence of such themes within a given setting over periods of time. We therefore investigated delusional themes across 12 years of presentation to a catchment-based early intervention service for first episode psychosis (FEP)., Methods: Systematically collected data from 500 patients at an early intervention service for FEP were analyzed. Four cohorts of 3 years each, from 2006 to 2017, were used to compare the frequency of delusion themes across cohorts. We also integrated into the analysis baseline sociodemographic factors such as gender, age, and highest level of education and clinical factors such as anxiety, depression, suicidality, hallucinations, and primary diagnosis (affective or non-affective psychosis)., Results: Sex and education level were stable across cohorts, while patient age varied (p = 0.047). Clinical anxiety, depression, and suicidality at entry were also stable. Across cohorts, the proportion of patients with affective versus non-affective diagnosis differed (p = 0.050), with no differences in global rating of delusion severity or theme prevalence except for delusions of guilt or sin (p = 0.001). This single theme difference was not correlated with age or diagnosis., Conclusion: Our study suggests relatively stable prevalence of delusion themes across cohorts of individuals experiencing FEP. This demonstrates the potential utility of studying thematic content both for understanding delusions in clinical populations and in research. Future explorations of the relationships between delusion themes and across individual patient episodes should be conducted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Relapse after first-episode psychosis (FEP) is a major clinical challenge for specialized early intervention services. Understanding patient perspectives on factors contributing to relapse can inform the development of risk assessments and preventive interventions. The objective of this study was to identify factors that may contribute to and prevent relapse from the perspectives of patients receiving services for FEP. Data from 25 participants across four focus groups in Canada were analyzed with a descriptive content analysis approach. Twelve factors were identified, of which four (social environment, technology use, medication, and lifestyle behaviors) had both contributory and preventive roles. In descending order of frequency, risk factors for relapse included substance use; unsupportive social environment; technology use; taking and not taking medication; lack of sleep; work, career, or school stress; significant life events; symptoms of depression or mania; generalized worry; and financial stress. Preventive factors consisted of having a supportive social environment, using technology, taking medication, using coping strategies, and engaging in healthy lifestyle behaviors and meaningful activities. These findings extend the literature on relapse vulnerability and protective factors. Importantly, the factors identified in this study are modifiable, and thereby provide insights for the development and optimization of relapse risk assessments and preventive interventions.

Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes., Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life., Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits., Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235 (41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR = 2.141, p  = 0.021), severe nicotine dependence (aOR = 2.906, p  < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR = 2.297, p  = 0.001), positive symptoms (aOR = 1.052, p  = 0.006), current major depressive episode (aOR = 2.627, p  < 0.001), sleep disorders (aOR = 1.474, p  = 0.024) and lower medication adherence (aOR = 0.836, p  = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder., Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia.

Schizophrenia is an illness characterized by positive symptoms, negative symptoms, and cognitive impairments. Cognitive impairments occur before the onset of psychosis and could reflect glutamatergic dysregulation. Thus, identifying associations between genetic variations in genes coding for glutamatergic receptors and cognitive impairment in schizophrenia may help in understanding the basis of these deficits and in identifying potential drug targets. In a discovery cohort of 144 first-episode of psychosis patients (FEP), we genotyped 58 candidate Single Nucleotide Polymorphisms (SNPs) located in NMDA and metabotropic glutamatergic receptors. These SNPs were selected according to the results from the Psychiatric Genomic Consortium and were tested for association with intellectual quotient (IQ) as assessed with the Wechsler Intelligence Scales. For replication, we used the ICAAR cohort including 121 ultra-high-risk patients (UHR) with the same cognitive assessment. A polymorphism located in GRM7, rs1396409, was significantly associated with performance IQ in the discovery cohort of FEP. This association was replicated in the UHR cohort. This polymorphism is also associated with total IQ and verbal IQ in the merged dataset, with a predominant effect on the arithmetic subtest. The rs1396409 polymorphism is significantly associated with cognitive impairment during the onset of psychosis. This genetic association highlights the possible impact of glutamatergic genes in cognitive deficits in the early phases of psychosis and enforces the interest for new therapeutic interventions targeting the glutamatergic pathway., Competing Interests: Declaration of competing interest Dr. Joober reports to be a speaker and/or consulting committee member for Pfizer, Janssen, BMS, Sunovian, Myelin, Otsuka, Lundbeck, shire and Perdue, and to have received grants from Janssen, BMS, Otsuka, Lundbeck, Astra Zeneca and HLS, and to have royalties from Henry Stewart talks, all outside the submitted work. Dr. Malla served as a research consultant to and gave lectures at conferences supported by Lundbeck and Otsuka and was on an advisory board meeting for the same two companies for which he received honoraria. Pr. Krebs has received honoraria from and participated in advisory boards or did educational conference for F. Hoffmann-La Roche, Janssen Cilag and Otsuka-Lundbeck. She received financial support for investigator-driven educational initiative from Eisai, Janssen Cilag and Otsuka-Lundbeck. Dr. Lepage reports grants from Otsuka Lundbeck Alliance, personal fees from Otsuka Canada, personal fees from Lundbeck Canada, grants and personal fees from Janssen, personal fees from MedAvante-Prophase, personal fees from Amplexor, outside the submitted work. Dr. Chaumette has received speaking fees from Janssen Cilag, outside the submitted work. All authors declare they have no conflict of interest related to this article. The contributing Group members (ICAAR study group) declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The neural orphan G protein coupled receptor GPR88 is predominant in the striatum and cortex of both rodents and humans, and considered a potential target for brain disorders. Previous studies have shown multiple behavioral phenotypes in Gpr88 knockout mice, and human genetic studies have reported association with psychosis. Here we tested the possibility that GPR88 contributes to Attention Deficit Hyperactivity Disorder (ADHD). In the mouse, we tested Gpr88 knockout mice in three behavioral paradigms, best translatable between rodents and humans, and found higher motor impulsivity and reduced attention together with the reported hyperactivity. Atomoxetine, a typical ADHD drug, reduced impulsivity in mutant mice. Conditional Gpr88 knockout mice in either D1R-type or D2R-type medium spiny neurons revealed distinct implications of the two receptor populations in waiting and stopping impulsivity. Thus, animal data demonstrate that deficient GPR88 activity causally promotes ADHD-like behaviors, and identify circuit mechanisms underlying GPR88-regulated impulsivity. In humans, we performed a family-based genetic study including 567 nuclear families with DSM-IV diagnosis of ADHD. There was a minor association for SNP rs2036212 with diagnosis, treatment response and cognition. A stronger association was found for SNP rs2809817 upon patient stratification, suggesting that the T allele is a risk factor when prenatal stress is involved. Human data therefore identify GPR88 variants associated with the disease, and highlight a potential role of life trajectories to modulate GPR88 function. Overall, animal and human data concur to suggest that GPR88 signaling should be considered a key factor for diagnostic and treatment of ADHD., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Persistent negative symptoms (PNS) are linked to poor functional outcomes and may be primary or caused by secondary factors. Although several studies have examined PNS in first-episode psychosis (FEP), a comparison with a data-driven approach is lacking. Here, we compared clinically defined PNS subgroups with class trajectories identified through latent growth modeling (LGM). Patients admitted to an early intervention service (N = 392) were classified as PNS (n = 105), secondary PNS (sPNS; n = 74), or non-PNS (n = 213) based on longitudinal data collected six to twelve months after admission. LGM was used to stratify patients based on similar negative symptom course over the same time period. Using multiple linear regression, we assessed the utility of both approaches in predicting Social and Occupational Functioning Assessment Scale (SOFAS) scores at two-year follow-up. Three negative symptom trajectories were identified: low and remitting (LR; n = 158), moderate and improving (MI; n = 163) and delayed partial response (DR; n = 71). Most non-PNS patients followed the LR trajectory, while patients with PNS or sPNS were generally divided between MI and DR. Both PNS classification and trajectory membership were significant predictors of two-year functional outcomes; the DR and MI trajectories predicted greater increases in SOFAS scores (DR: b = -19.14; MI: b = -11.54) than either sPNS (b = -9.19) or PNS (b = -6.46). These findings demonstrate that combining PNS and symptom-based stratification can predict functional outcomes more accurately than either taxonomy alone. Such a combined approach could yield significant advances in developing more targeted interventions for patients at risk for poor functional outcomes., Competing Interests: Conflicts of interest Salary awards include: FRSQ to R.J., and M.L.; a Canada Research Chair to A.M.; and a James McGill Professorship to M.L. M.L. reports grants from Otsuka Lundbeck Alliance and diaMentis, personal fees from Otsuka Canada, personal fees from Lundbeck Canada, grants and personal fees from Janssen, and personal fees from MedAvante-Prophase, outside the submitted work. R.J. reports receipt of grants, as well as speaker's and consultant's honoraria from Janssen, Lundbeck, Otsuka, Pfizer, Shire, Perdue, HLS and Myelin and royalties from Henry Stewart Talks. A.M. reports research funding for an investigator-initiated project from BMS Canada and honoraria for lectures and consulting activities (e.g., advisory board participation) with Otsuka and Lundbeck, all unrelated to the present article. All other authors report no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Given the paucity of functional recovery measures for young people with psychosis, we developed and conducted psychometric testing of the Functional Outcomes Interview (FOI) and the Roles and Aspirations Among Youth scale (RAY; a much-needed patient-reported outcome measure)., Method: Both measures were developed in English, Tamil, and French through discussions with professionals, participants, and families at early psychosis programs in Canada and India. The FOI assesses the number and tenure of functional roles and allows the nuanced assessment of each role in terms of performance, need for support, and quality of social contacts. The roles include work, school, household responsibilities, parenting/caregiving, and efforts to return to work/school. The RAY is a self-report of current roles and future aspirations. Test-retest reliability, internal consistency, factorial validity, and concurrent validity for the RAY; and inter-rater reliability (IRR), internal consistency, and concurrent validity for the FOI were assessed., Results: The RAY had adequate internal consistency and temporal stability and was unidimensional in factor analysis. The FOI had acceptable IRR and internal consistency, as evinced by comparable performance ratings across functional roles. Significant associations between our novel measures and well-established measures of functioning and negative symptoms indicate concurrent validity., Conclusions and Implications for Practice: The FOI and RAY were designed to be youth friendly, assess aspirations, and acknowledge individuals as desiring and holding multiple roles. They thus represent a significant advancement in assessing functional recovery in first-episode psychosis. Having been tested in two distinct settings, these measures show promise for wider deployment across geo-cultural contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Verbal memory (VM) dysfunction is prevalent in first-episode psychosis (FEP) and has major impacts on long-term functional and clinical outcomes. Nevertheless, a substantial proportion of FEP patients have VM performance in the norm, called normal-range (NR) VM, and only a few studies have explored its relation to outcomes. Moreover, probable decrements between estimated premorbid and current cognitive performance could confuse the relationship between VM and clinical or functional outcomes in FEP patients. These potential interactions have not yet been considered in FEP, thus, we examined 1) the longitudinal relationship between VM performance (NR vs. below NR (BNR)) in FEP and clinical and functional outcomes over 24 months following admission to treatment, and 2) compared the clinical and functional status of NR patients with and without cognitive decrement at baseline and 12 months. A total of 271 patients (BNR = 114, NR = 157; 81 out of 105 NR with decrement) completed measures of psychosocial functioning and clinical symptoms at baseline, month 12, and month 24. Generalized Estimating Equations and unpaired t-tests were used to address the first and second aim, respectively. NR demonstrated better functioning and fewer negative symptoms when compared to BNR. Interestingly, NR patients with decrement reported significantly more negative symptoms at baseline compared to their counterparts without decrement. These findings document that a large proportion (57.9 %) of FEP patients have NR VM that appear to be functionally advantageous but that NR VM is nuanced by the presence or absence of a potential decrement early in the developmental course of the disorder., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Attention Deficit/Hyperactivity Disorder (ADHD) has been associated with atypical patterns of neural activity measured by electroencephalography (EEG). However, the identification of EEG diagnostic biomarkers has been complicated by the disorder's heterogeneity. The objective of this review was to synthesize the literature investigating EEG variation in patients diagnosed with ADHD, addressing the following questions: 1) Are the diagnostic ADHD subtypes associated with different EEG characteristics? 2) Are EEG measures correlated with ADHD traits and/or symptom severity? and 3) Do classification techniques using EEG measures reveal different clinical presentations of ADHD? Outcomes highlight the potential for electrophysiological measures to provide meaningful insights into the heterogeneity of ADHD, although direct translation of EEG biomarkers for diagnostic purposes is not yet supported. Key measures that show promise for the discrimination of existing ADHD subtypes and symptomatology include: resting state and task-related modulation of alpha, beta and theta power, and the event-related N2 and P3 components. Prescriptions are discussed for future studies that may help to bridge the gap between research and clinical application., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia., Aims: We sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis., Method: Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations., Results: In left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS., Conclusions: The current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences in hippocampal-cortical circuitry and their associations with different behavioral dimensions may be useful for understanding the underlying pathophysiology of verbal memory deficits and related symptomatology in psychosis. Here, we use a data-driven approach to simultaneously capture the complex links between sex, verbal memory, symptoms, and cortical-hippocampal brain metrics in FEP. Structural magnetic resonance imaging and behavioral data were acquired from 100 FEP patients (75 males, 25 females) and 87 controls (55 males, 32 females). Multivariate brain-behavior associations were examined in FEP using partial least squares to map sociodemographic, verbal memory, and clinical data onto brain morphometry. The analysis identified two sex-dependent patterns of verbal memory, symptoms, and brain structure. In male patients, verbal memory deficits and core psychotic symptoms were associated with both increased and decreased frontal and temporal cortical thickness and reductions in CA2/3 hippocampal subfield and fornix volumes. In female patients, fewer negative/depressive symptoms were associated with a more attenuated cortical thickness pattern and more diffuse reductions in hippocampal white matter regions. Taken together, the results contribute towards better understanding the underlying pathophysiology of psychosis by highlighting the unique contribution of specific hippocampal subfields and surrounding white matter and their connections with broader cortical networks in a sex-dependent manner., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To study the impact of supervised antipsychotic medication discontinuation on clinical and functional outcomes in first-episode psychosis (FEP) in two different cultural environments., Method: FEP patients(N = 253), treated in two early intervention services (Montreal, Canada and Chennai, India) for 2 years, were assessed for medication use, positive and negative symptom remission and social-occupational functioning at regular intervals., Results: Between months 4 and 24 of treatment, 107 patients discontinued medication ('Off'group) as compared to 146 who stayed on medication ('On'group). Medication discontinuation was higher in Chennai as compared to Montreal (n = 80, 49.07% vs n = 27, 16.87%; χ 2 37.80, p < 0.001), with no difference in time to discontinuation [Means(SDs) = 10.64(6.82) and 10.04(5.43), respectively, p = 0.71). At month 24 (N = 235), there were no differences in the rate of positive symptom remission between the on and Off groups (81.5 vs 88.0%, respectively) at both sites. The rate of negative symptom remission was lower among patients in the On compared to the Off group (63.2 vs 87.9%, respectively, χ 2  = 17.91, p < 0.001), but only in Montreal (55.4% vs 80.0%, respectively, χ 2  = 4.12, p < 0.05). Social and Occupational Functioning Assessment Scale scores were equally high in both Off and On medication groups in Chennai [Means (SDs) = 79.43(12.95) and 73.59(17.63), respectively] but higher in the Off compared to the On group in Montreal Means (SDs) = 77.47(14.97) and 64.94(19.02), respectively; Time × site interaction F = 3.96(1,217), p < 0.05]. Medication status (On-Off) had no impact on the outcomes, independent of other variables known to influence outcomes., Conclusion: Certain cultural environments and patient characteristics may facilitate supervised discontinuation of antipsychotic medication following treatment of an FEP without negative consequences., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aim: To compare social, recreational and independent functioning among persons with psychosis across two geo-cultural contexts, we adapted the well-established Social Functioning Scale (SFS) and translated it into French and Tamil. We present the development and psychometric testing of this adaptation, the SFS-Early Intervention., Methods: Sixteen items were added to reflect contemporary youth activities (e.g., online games) and 31 items adapted to enhance applicability and/or include context-specific examples (e.g., 'church activity' replaced with 'religious/spiritual activity'). Psychometric properties and participant feedback were evaluated., Results: Test-retest reliability (ICCs) ranged from 0.813 to 0.964. Internal consistency (Cronbach's α) ranged from .749 to .936 across sites and languages. Correlations with original subscales were high. The scale was rated easy to complete and understand., Conclusions: The SFS-Early Intervention is a promising patient-reported measure of social, recreational and independent functioning. Our approach shows that conceptually sound existing measures are adaptable to different times and contexts., (© 2021 John Wiley & Sons Australia, Ltd.)

Introduction: Adherence to therapeutic guidelines in psychiatry is anchored and facilitated by rating scales. However, they are rarely used in routine care, particularly for psychotic disorders. Consequently, adherence to treatment guidelines are not ideal and patient outcomes are often sub-optimal. In this study, we used the clinician-rated Clinical Global Impressions Scale (CGI) to implement a measurement-based care (MBC) approach and derive indices of quality of care at a first episode psychosis (FEP) program., Methods: At the individual level, an algorithm was created using CGI scores and their changes over time to define the concept of Patient Requiring Clinical Attention (PRCA) that encompasses several categories (e.g. episode of severity, treatment inertia, or treatment resistance). At the service level, CGI scores were used to derive several indices of quality of care: severity of illness and its change over time, conformity to the use of low doses of antipsychotic medications, and clozapine offer index., Results: 135 Patients were included in this study of whom 19 patients were identified as PRCA. Of these, 12 (63%) received timely medication, and 7 (37%) were suspected cases of therapeutic inertia. Additionally, 15 patients met criteria for treatment resistance of whom 7 were offered clozapine (47%). At the service level, the average CGI improved by 2 points from baseline to month 1 and average doses of antipsychotic medications prescribed were in line with prescription guidelines for FEP patients., Conclusion: The proposed CGI-based treatment algorithm and service evaluation strategy can help to optimize quality care and services for patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: It is unknown whether patient disengagement from early intervention services for psychosis is as prevalent in low- and middle-income countries (LMICs) like India, as it is in high-income countries (HICs). Addressing this gap, we studied two first-episode psychosis programs in Montreal, Canada and Chennai, India. We hypothesized lower service disengagement among patients and higher engagement among families in Chennai, and that family engagement would mediate cross-site differences in patient disengagement., Methods: Sites were compared on their 2-year patient disengagement and family engagement rates conducting time-to-event analyses and independent samples t tests on monthly contact data. Along with site and family involvement, Cox proportional hazards regression included known predictors of patient disengagement (e.g. gender)., Results: The study included data about 333 patients (165 in Montreal, 168 in Chennai) and their family members (156 in Montreal, 168 in Chennai). More Montreal patients (19%) disengaged before 24 months than Chennai patients (1%), χ 2 (1, N = 333) = 28.87, p < 0.001. Chennai families had more contact with clinicians throughout treatment (Cohen's d = -1.28). Family contact significantly predicted patient disengagement in Montreal (HR = 0.87, 95% CI 0.81-0.93). Unlike in Chennai, family contact declined over time in Montreal, with clinicians perceiving such contact as not necessary (Cohen's d = 1.73)., Conclusions: This is the first investigation of early psychosis service engagement across a HIC and an LMIC. Patient and family engagement was strikingly higher in Chennai. Maintaining family contact may benefit patient engagement, irrespective of context. Findings also suggest that differential service utilization may underpin cross-cultural variations in psychosis outcomes.

Introduction: Measurement-based care (MBC) is an evidence-based practice wherein clinical decisions are informed by patient data collected throughout treatment. MBC has yielded superior patient outcomes compared to standard care. However, the implementation of MBC in the day-to-day practice, particularly in psychotic disorders, poses several challenges. This study evaluates the clinician-rated Clinical Global Impressions Scale of Severity (CGI-S), for MBC implementation at a first-episode psychosis program., Methods: The CGI-S was evaluated in the context of routine care on fidelity to practice, inter-rater reliability among psychiatrists and concurrent validity with scales measuring different domains of psychopathology (SAPS, SANS, GAF, BPRS, PANSS-6)., Results: A high fidelity to practice (67%) and inter-rater reliability was found (r wg  = 0.92). CGI-S correlations were significant and strongest with BPRS (r = 0.55; p < 0.01), GAF (r = 0.53; p < 0.01), SAPS (r = 0.52, p < 0.01), and PANSS-6 (r = 0.41; p < 0.05) scores. However, correlations with SANS and PANSS-6 Negative sub-scale were weak., Conclusion: Findings suggest the CGI may be used to overcome important barriers towards MBC implementation within the context of first episode psychosis. However, as suggested by data, further improvements in capturing negative symptoms by rating clinicians are needed., Twitter: A novel strategy for measurement-based care to optimize treatment for individuals with first episode psychosis and related psychotic disorders., (Copyright © 2022. Published by Elsevier B.V.)

Ownership of cats in childhood has been inconsistently associated with psychosis in adulthood. Parasitic exposure, the putative mechanism of this association, may be more common with rodent-hunting cats, and its association with psychosis may depend on other environmental exposures. We examined the conditional associations between childhood cat ownership and the frequency of psychotic experiences in adulthood. Adults (n = 2206) were recruited in downtown Montreal to complete a survey about childhood cat ownership (non-hunting or rodent-hunting), winter birth, residential moves in childhood, head trauma history, and tobacco smoking. The frequency of psychotic experiences (PE) was measured with the 15-item positive subscale of the Community Assessment of Psychic Experiences. Associations between exposures and PE were examined in linear regressions adjusted for age and sex. Interactions among variables were explored using a conditional inference tree. Rodent-hunting cat ownership was associated with higher PE scores in male participants (vs. non-hunting or no cat ownership: SMD = 0.57; 95% CI: 0.27, 0.86), but not in female participants (SMD = 0.10; 95% CI: -0.18, 0.38). In the conditional inference tree, the highest mean PE score was in the class comprised of non-smokers with >1 residential move, head trauma history, and rodent-hunting cat ownership (n = 22; mean standard score = 0.96). The interaction between rodent-hunting cat ownership and head trauma history was supported by a post-hoc linear regression model. Our findings suggest childhood cat ownership has conditional associations with psychotic experiences in adulthood., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Apart from increasing risk for psychotic disorders, childhood adversity has been associated with worse outcomes. One way in which childhood adversity may worsen outcomes is by lengthening treatment delays, which are associated with negative impacts. We tested the influence of childhood trauma on treatment delays, measured as the duration of untreated psychosis (DUP), and its help-seeking and referral components, in a first-episode psychosis cohort (N = 203). We accounted for pertinent social (e.g., migrant status) and other determinants (i.e., age at onset, diagnosis, symptoms) of treatment delays. Multiple linear regression analyses revealed that for a one-unit increase in Childhood Trauma Questionnaire (CTQ) scores, average overall DUP increased by 25%. Higher CTQ scores also significantly predicted help-seeking and referral DUPs. Patients with schizophrenia-spectrum psychosis had longer help-seeking and total DUPs than those with affective psychosis. More severe positive symptoms predicted longer help-seeking DUPs, while more severe negative symptoms predicted longer referral DUPs. Indicators of social disadvantage did not affect DUP. Our results show that childhood trauma increases DUP by prolonging the help-seeking process and delaying access to mental healthcare even after help is sought. Early identification of psychosis among populations with trauma histories seems warranted and can likely positively impact outcomes., (Copyright © 2021. Published by Elsevier B.V.)

Persistent negative symptoms (PNS) are an important factor of first episode of psychosis (FEP) that present early on in the course of illness and have a major impact on long-term functional outcome. Lack of clinical insight is consistently associated with negative symptoms during the course of schizophrenia, yet only a few studies have explored its evolution in FEP. We sought to explore clinical insight change over a 24-month time period in relation to PNS in a large sample of FEP patients. Clinical insight was assessed in 515 FEP patients using the Scale to assess Unawareness of Mental Disorder. Data on awareness of illness, belief in response to medication, and belief in need for medication were analyzed. Patients were divided into 3 groups based on the presence of negative symptoms: idiopathic (PNS; n = 135), secondary (sPNS; n = 98), or absence (non-PNS; n = 282). Secondary PNS were those with PNS but also had clinically relevant levels of positive, depressive, or extrapyramidal symptoms. Our results revealed that insight improved during the first 2 months for all groups. Patients with PNS and sPNS displayed poorer insight across the 24-month period compared to the non-PNS group, but these 2 groups did not significantly differ. This large longitudinal study supported the strong relationship known to exist between poor insight and negative symptoms early in the course of the disorder and probes into potential factors that transcend the distinction between idiopathic and secondary negative symptoms., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Individuals with mental health problems have multiple, often inadequately met needs. Responsibility for meeting these needs frequently falls to patients, their families/caregivers, and governments. Little is known about stakeholders' views of who should be responsible for these needs and there are no measures to assess this construct. This study's objectives were to present the newly designed Whose Responsibility Scale (WRS), which assesses how stakeholders apportion responsibility to persons with mental health problems, their families, and the government for addressing various needs of persons with mental health problems, and to report its psychometric properties., Methods: The 22-item WRS asks respondents to assign relative responsibility to the government versus persons with mental health problems, government versus families, and families versus persons with mental health problems for seven support needs. The items were modelled on a World Values Survey item comparing the government's and people's responsibility for ensuring that everyone is provided for. We administered English, Tamil, and French versions to 57 patients, 60 family members, and 27 clinicians at two early psychosis programs in Chennai, India, and Montreal, Canada, evaluating test-retest reliability, internal consistency, and ease of use. Internal consistency estimates were also calculated for confirmatory purposes with the larger samples from the main comparative study., Results: Test-retest reliability (intra-class correlation coefficients) generally ranged from excellent to fair across stakeholders (patients, families, and clinicians), settings (Montreal and Chennai), and languages (English, French, and Tamil). In the standardization and larger confirmatory samples, internal consistency estimates (Cronbach's alphas) ranged from acceptable to excellent. The WRS scored average on ease of comprehension and completion. Scores were spread across the 1-10 range, suggesting that the scale captured variations in views on how responsibility for meeting needs should be distributed. On select items, scores at one end of the scale were never endorsed, but these reflected expected views about specific needs (e.g., Chennai patients never endorsed patients as being substantially more responsible for housing needs than families)., Conclusions: The WRS is a promising measure for use across geo-cultural contexts to inform mental health policies, and to foster dialogue and accountability among stakeholders about roles and responsibilities. It can help researchers study stakeholders' views about responsibilities, and how these shape and are shaped by sociocultural contexts and mental healthcare systems., (© 2022. The Author(s).)

Background: Individuals with mental health problems have many insufficiently met support needs. Across sociocultural contexts, various parties (e.g., governments, families, persons with mental health problems) assume responsibility for meeting these needs. However, key stakeholders' opinions of the relative responsibilities of these parties for meeting support needs remain largely unexplored. This is a critical knowledge gap, as these perceptions may influence policy and caregiving decisions., Methods: Patients with first-episode psychosis (n = 250), their family members (n = 228), and clinicians (n = 50) at two early intervention services in Chennai, India and Montreal, Canada were asked how much responsibility they thought the government versus persons with mental health problems; the government versus families; and families versus persons with mental health problems should bear for meeting seven support needs of persons with mental health problems (e.g., housing; help covering costs of substance use treatment; etc.). Two-way analyses of variance were conducted to examine differences in ratings of responsibility between sites (Chennai, Montreal); raters (patients, families, clinicians); and support needs., Results: Across sites and raters, governments were held most responsible for meeting each support need and all needs together. Montreal raters assigned more responsibility to the government than did Chennai raters. Compared to those in Montreal, Chennai raters assigned more responsibility to families versus persons with mental health problems, except for the costs of substance use treatment. Family raters across sites assigned more responsibility to governments than did patient raters, and more responsibility to families versus persons with mental health problems than did patient and clinician raters. At both sites, governments were assigned less responsibility for addressing housing- and school/work reintegration-related needs compared to other needs. In Chennai, the government was seen as most responsible for stigma reduction and least for covering substance use services., Conclusions: All stakeholders thought that governments should have substantial responsibility for meeting the needs of individuals with mental health problems, reinforcing calls for greater government investment in mental healthcare across contexts. The greater perceived responsibility of the government in Montreal and of families in Chennai may both reflect and influence differences in cultural norms and healthcare systems in India and Canada., (© 2022. The Author(s).)

Objective: To investigate whether first-episode psychosis patients receiving extended early intervention had better functional outcomes than those in regular care and to examine the predictors of functional outcomes., Methods: This is a randomized controlled single-blind trial of 220 patients randomized after 2 years of early intervention to receive early intervention or regular care for the subsequent 3 years. Outcomes included cumulative time in functional recovery during the 3-year trial assessed using the Social and Occupational Functioning Assessment Scale (SOFAS); and employment/education at last assessment which were, respectively, analyzed using multiple linear regression and logistic regression, accounting for well-known predictors. Linear mixed and generalized linear models were also used to examine the course of SOFAS and employment/education over the 3-year period., Results: The extended early intervention and regular care groups did not differ on time in functional recovery (mean = 50.17 weeks, SD = 46.62 vs. mean = 46.18 weeks, SD = 51.54); percent employed/in school (60.4% vs. 68.8%) or change in SOFAS or employment/education status over time. SOFAS scores were stable between years 2 and 5. Individuals with longer periods of total symptom remission experienced significantly longer periods of functional recovery and were likelier to be employed/in school. Those who had completed high school were nine times likelier to be employed/studying., Conclusion: Most individuals maintained functional gains accrued from 2 years of early intervention with no further improvement whether in extended early intervention or regular care. There was a gap between symptomatic and functional recovery, and one-third were unemployed/not in school at year 5. The lack of additional progress even in extended early intervention suggests that specific interventions addressing functional roles need to be provided beyond the first 2 years of early intervention. Sustaining symptom remission and high-school completion may be additional avenues for targeting functional recovery., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Psychotic disorders are among the most disabling of all mental disorders. The first-episode psychosis (FEP) often occurs during adolescence or young adulthood. Young people experiencing FEP often face multiple barriers in accessing a comprehensive range of psychosocial services, which have predominantly been delivered in person. New models of service delivery that are accessible, sustainable, and engaging are needed to support recovery in youth diagnosed with FEP., Objective: In this paper, we describe a protocol to implement and evaluate the acceptability, safety, and potential efficacy of an online psychosocial therapeutic intervention designed to sustain recovery and prevent relapses in young adults diagnosed with FEP. This intervention was originally developed and tested in Australia and has been adapted for implementation and evaluation in Canada and is called Horyzons-Canada (HoryzonsCa)., Methods: This cohort study is implemented in a single-center and applies a pre-post mixed methods (qualitative-quantitative convergent) design. The study involves recruiting 20 participants from a specialized early intervention program for psychosis located in Montreal, Canada and providing them with access to the HoryzonsCa intervention for 8 weeks. Data collection includes interview-based psychometric measures, self-reports, focus groups, and interviews., Results: This study received funding from the Brain and Behavior Research Foundation (United States), the Quebec Health Research Funding Agency (Canada), and the Canada Research Chairs Program. The study was approved by the Research Ethics Board of the Centre intégré universitaire de santé et de services sociaux de l'Ouest-de-l'Île-de-Montréal on April 11, 2018 (#IUSMD 17-54). Data were collected from August 16, 2018, to April 29, 2019, and a final sample of 20 individuals participated in the baseline and follow-up interviews, among which 9 participated in the focus groups. Data analysis and reporting are in process. The results of the study will be submitted for publication in 2021., Conclusions: This study will provide preliminary evidence on the acceptability, safety, and potential efficacy of using a digital health innovation adapted for the Canadian context to deliver specialized mental health services to youth diagnosed with FEP., Trial Registration: ISRCTN Registry ISRCTN43182105; https://www.isrctn.com/ISRCTN43182105., International Registered Report Identifier (irrid): RR1-10.2196/28141., (©Shalini Lal, John F Gleeson, Simon D'Alfonso, Geraldine Etienne, Ridha Joober, Martin Lepage, Hajin Lee, Mario Alvarez-Jimenez. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 07.12.2021.)

Background: There is limited empirical data quantifying the utility of genetic testing for families of children with autism spectrum disorder (ASD) or related neurodevelopmental disorders (NDD). We assessed the utility of clinical chromosomal microarray analysis (CMA), defined by diagnostic yield and parental empowerment, in population-based sample of parents of affected children; and explored child, family, and health services factors predictive of empowerment., Methods: Participants were families of children undergoing diagnostic assessments, between 2016 and 2019. Diagnostic yield of CMA in affected children was determined. Parental empowerment was measured through adapted version of the Genetics Counseling Outcome Scale-24. Parents completed questionnaires to capture child, family, and health service factors., Results: The diagnostic yield of CMA was 2.8% for pathogenic variants. Parental empowerment was significantly correlated with family functioning and aspects of perceived family-centeredness of care. The model accounted for 49.8% of the variation in parental empowerment, F (10,37) = 3.67, p = 0.002. After accounting for other predictors, parental perception of the provision of general information remained significantly associated with empowerment., Conclusion: The informational needs of families play an important role in their empowerment during genetic testing. Meeting these needs and monitoring empowerment can aid genomic technologies integration in personalized healthcare for ASD/NDD., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

People can navigate in a new environment using multiple strategies dependent on different memory systems. A series of studies have dissociated between hippocampus-dependent 'spatial' navigation and habit-based 'response' learning mediated by the caudate nucleus. The val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene leads to decreased secretion of BDNF in the brain, including the hippocampus. Here, we aim to investigate the role of the BDNF val66met polymorphism on virtual navigation behaviour and brain activity in healthy older adults. A total of 139 healthy older adult participants (mean age = 65.8 ± 4.4 years) were tested in this study. Blood samples were collected, and BDNF val66met genotyping was performed. Participants were divided into two genotype groups: val homozygotes and met carriers. Participants were tested on virtual dual-solution navigation tasks in which they could use either a hippocampus-dependent spatial strategy or a caudate nucleus-dependent response strategy to solve the task. A subset of the participants (n = 66) were then scanned in a 3T functional magnetic resonance imaging (fMRI) scanner while engaging in another dual-solution navigation task. BDNF val/val individuals and met carriers did not differ in learning performance. However, the two BDNF groups differed in learning strategy. BDNF val/val individuals relied more on landmarks to remember target locations (i.e., increased use of flexible spatial learning), while met carriers relied more on sequences and patterns to remember target locations (i.e., increased use of inflexible response learning). Additionally, BDNF val/val individuals had more fMRI activity in the hippocampus compared with BDNF met carriers during performance on the navigation task. This is the first study to show in older adults that BDNF met carriers use alternate learning strategies from val/val individuals and to identify differential brain activation of this behavioural difference between the two groups., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: Examining the joint effect of two functional variants in two dopamine-related genes ( DRD3 and COMT ) on ADHD-relevant behaviors under three experimental conditions (EC)., Method: 362 children with ADHD were assessed by parents and teachers during a week of baseline evaluation, followed by 1 week of MPH and placebo, administered in a double-blind crossover design., Results: Statistically significant 3-way ( DRD3 -by- COMT -by-EC; p = .004) and 2-way interactions ( COMT by EC; p = .002) were observed on Conners'-Teachers scores. Children with the COMT Met/Met genotype had lower scores at baseline and on placebo compared to the other genotype groups. Furthermore, stratifying the children according to their COMT genotypes helped to detect statistically significant and biologically meaningful effects of DRD3 genotype., Conclusions: These findings suggest that COMT and DRD3 genetic variants may together play a role in ADHD symptomatology and response to treatment through gene-gene interaction.

Intellectual disability (ID) encompasses a clinically and genetically heterogeneous group of neurodevelopmental disorders that may present with psychiatric illness in up to 40% of cases. Despite the evidence for clinical utility of genetic panels in pediatrics, there are no published studies in adolescents/adults with ID or autism spectrum disorder (ASD). This study was approved by our institutional research ethics board. We retrospectively reviewed the medical charts of all patients evaluated between January 2017 and December 2019 in our adult neuropsychiatric genetics clinic at the McGill University Health Centre (MUHC), who had undergone a comprehensive ID/ASD gene panel. Thirty-four patients aged > 16 years, affected by ID/ASD and/or other neuropsychiatric/behavioral disorders, were identified. Pathogenic or likely pathogenic variants were identified in one-third of our cohort (32%): 8 single-nucleotide variants in 8 genes (CASK, SHANK3, IQSEC2, CHD2, ZBTB20, TREX1, SON, and TUBB2A) and 3 copy number variants (17p13.3, 16p13.12p13.11, and 9p24.3p24.1). The presence of psychiatric/behavioral disorders, regardless of the co-occurrence of ID, and, at a borderline level, the presence of ID alone were associated with positive genetic findings (p = 0.024 and p = 0.054, respectively). Moreover, seizures were associated with positive genetic results (p = 0.024). One-third of individuals presenting with psychiatric illness who met our red flags for Mendelian diseases have pathogenic or likely pathogenic variants which can be identified using a comprehensive ID/ASD gene panel (~ 2500 genes) performed on an exome backbone., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Clinical, functional, and cost-effectiveness outcomes from early intervention services (EIS) for psychosis are significantly associated with the duration of untreated psychosis (DUP) for the patients they serve. However, most EIS patients continue to report long DUP, while a reduction of DUP may improve outcomes. An understanding of different components of DUP and the factors associated with them may assist in targeting interventions toward specific sources of DUP., Objectives: To examine the components of DUP and their respective determinants in order to inform strategies for reducing delay in treatment in the context of an EIS., Methods: Help-seeking (DUP-H), Referral (DUP-R), and Administrative (DUP-A) components of DUP, pathways to care, and patient characteristics were assessed in first episode psychosis ( N = 532) patients entering an EIS that focuses on systemic interventions to promote rapid access. Determinants of each component were identified in the present sample using multivariate analyses., Results: DUP-H (mean 25.64 ± 59.00) was longer than DUP-R (mean = 14.95 ± 45.67) and DUP-A (mean 1.48 ± 2.55). Multivariate analyses showed that DUP-H is modestly influenced by patient characteristics (diagnosis and premorbid adjustment; R = 0.12) and DUP-R by a combination of personal characteristics (age of onset and education) and systemic factors (first health services contact and final source of referral; 2 = 0.12) and DUP-R by a combination of personal characteristics (age of onset and education) and systemic factors (first health services contact and final source of referral; R = 0.08). Patients with health care contact prior to onset of psychosis had a shorter DUP-H and DUP-R than those whose first contact was after psychosis onset (F(1, 498) = 4.85, 2 = 0.21). Comorbid substance abuse and referral from hospital emergency services have a modest influence on DUP-A ( R 2 = 0.08). Patients with health care contact prior to onset of psychosis had a shorter DUP-H and DUP-R than those whose first contact was after psychosis onset (F(1, 498) = 4.85, P < 0.03 and F(1, 492) = 3.34, P < 0.07)., Conclusions: Although much of the variance in DUP is unexplained, especially for help-seeking component, the systemic portion of DUP may be partially determined by relatively malleable factors. Interventions directed at altering pathways to care and promote rapid access may be important targets for reducing DUP. Simplifying administrative procedures may further assist in reducing DUP.

Background: Tryptophan hydroxylase 2 (TPH2) is a key enzyme in the biosynthesis of serotonin in the brain. This study aims to investigate the role of a functional variant in TPH2 (rs17110747) in the pathophysiology of ADHD. This variant has been implicated in mood disorders in recent meta-analysis. This study uses a comprehensive approach that combines association testing and pharmaco-dynamic evaluation of behaviour, in a large sample of children with ADHD (n = 570)., Methods: The association between various ADHD relevant traits and rs17110747 was analyzed using family-based association tests (FBAT). Children were assessed by parents, teachers and research staff under three experimental conditions (EC): baseline, placebo, and methylphenidate using a double-blind placebo-controlled crossover trial., Outcomes: FBAT analysis conducted in a sample stratified based on sex of the proband, showed that there was a highly significant overtransmission of the G allele from parents to affected girls. In addition, significant association with several behavioral and cognitive dimensions of ADHD was observed only when the proband was female. Further, girls with the G/G genotype (rs17110747) had greater response to placebo when evaluated by parents., Interpretation: These results suggest that there may be a complex association of TPH2 in the etiology of ADHD, with a sex-specific effect., (Copyright © 2021. Published by Elsevier Inc.)

Aim: We investigated whether individuals varied in their satisfaction with being randomized to an extension of early intervention (EI) for psychosis or regular care after 2 years of EI, and whether satisfaction was associated with service engagement 3 years later., Methods: Following randomization, patients (N = 220) indicated if they were happy with, unhappy or indifferent to their group assignment. Follow-up with service providers was recorded monthly., Results: Patients randomized to extended EI were more likely to express satisfaction with their group assignment than those in the regular care group (88.2% vs 31.5%, χ 2 = 49.96, P < .001). In the extended EI group, those happy with their assigned group were likelier to continue seeing their case manager for the entire five-year period than those who were unhappy/indifferent (χ 2 = 5.61, P = .030)., Conclusions: Perceptions about EI, indicated by satisfaction with being assigned to extended EI, may have lasting effects on service engagement., (© 2020 John Wiley & Sons Australia, Ltd.)