@article{pmid42413522,

title = {Return on investment of enhanced primary youth mental health services in a large Canadian urban centre: a retrospective cohort study},

author = {Jai L Shah and Nguyen Xuan Thanh and Shireen Surood and Surya Poudel and Liana Urichuk and Giuseppe D'Andrea and Eric Latimer and Neil Andersson and Patricia Boksa and Ridha Joober and Shalini Lal and Srividya N Iyer and Ashok Malla and Philip Jacobs and },

doi = {10.1016/S2215-0366(26)00165-3},

issn = {2215-0374},

year  = {2026},

date = {2026-08-01},

journal = {Lancet Psychiatry},

volume = {13},

number = {8},

pages = {657--668},

abstract = {BACKGROUND: Many youth mental health reforms aim to shift care away from acute, hospital, or institutional settings and into community-based services, but few such initiatives have been subject to economic evaluations. We aimed to examine service utilisation and the corresponding return on investment for individuals receiving care via an enhanced primary-care youth mental health service.nnMETHODS: We conducted a retrospective cohort study of an enhanced primary-care youth mental health service transformation in a major urban site of the pan-Canadian ACCESS Open Minds network, which provides assessment and interventions for all types and severities of mental health problems, with priorities co-designed by individuals with lived experience (young people, families, and carers). Administrative datasets were used to determine service utilisation and the associated costs, including programme implementation, for help-seeking youth aged 15-25 years with any mental health problem. A difference-in-differences approach compared outcomes pre-exposure with outcomes post-exposure to the ACCESS Open Minds service over 1 year, in relation to youth receiving a non-transformed service. Propensity score matching and sensitivity analyses ensured bias reduction and robustness of observations, respectively.nnFINDINGS: Between April 6, 2016, and Sept 30, 2019, 10 632 help-seeking youth (4821 [45·4%] males and 5801 [54·6%] females) were included. 1415 youths (mean age 20·1 years) received care from ACCESS Open Minds, and 9217 youths (19·3 years) received standard community mental health services. No ethnicity data were available in this administrative dataset. Compared with those receiving services in community mental health clinics, those receiving ACCESS Open Minds had more intensive service needs throughout the study period and had greater and statistically significant reductions in hospital admissions (CA$1961 savings); outpatient ($613 savings), specialist ($432 savings), and general practitioner visits ($47 savings); and public residential admissions ($1256 savings) per-person per-year. There were no significant differences in emergency department visits, the number of prescriptions dispensed, community mental health visits, or contracted residential admissions. Net cost reduction associated with ACCESS Open Minds was $4355 per-person per-year, with implementation costs of $448, representing a net benefit of $3907 (return on investment 9·7).nnINTERPRETATION: Consistent with principles of early intervention in mental health, ACCESS Open Minds implementation resulted in improved or equivalent outcomes but also shifted care towards community-based settings, with substantial net cost savings. These cost savings can be realised if novel services identify and treat not only new cases but also include those who were previously intensive users of standard services. The long-term return on investment of enhanced primary youth mental health models such as ACCESS Open Minds will likely rest on their commitment to including this population.nnFUNDING: Canadian Institutes of Health Research and the Graham Boeckh Foundation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40971561,

title = {Subcategories of the Clinical High-Risk State for Psychosis and Their Relationship to a Full First-Episode Psychosis Sample: An Exploratory Analysis of Longitudinal Outcomes},

author = {Olivier Renaud-Charest and Vincent Paquin and Jean-Gabriel Daneault and Ashok K Malla and Ridha Joober and Srividya N Iyer and Martin Lepage and Jai L Shah},

doi = {10.1093/schbul/sbaf155},

issn = {1745-1701},

year  = {2026},

date = {2026-07-01},

journal = {Schizophr Bull},

volume = {52},

number = {4},

abstract = {BACKGROUND AND HYPOTHESIS: Subcategories of the Clinical High-Risk state for psychosis (CHR-P) have been associated with differential risk for transition to first-episode psychosis (FEP), but their relevance for longer term FEP outcomes remains unclear. We aimed to determine the prevalence of 2 CHR-P subcategories - attenuated psychotic symptoms (APS) and brief intermittent psychotic symptoms (BIPS) - in a full sample of FEP patients, along with their association with outcome trajectories following psychosis onset.nnSTUDY DESIGN: Participants were recruited from an early intervention service and followed over 2 years, with repeated measures of psychotic symptoms, affective symptoms, and functioning. Pre-onset symptoms were assessed using follow-back methods to reconstruct subgroups and their prevalence within the sample. Linear mixed models were applied to examine associations between putative CHR-P subcategories and longitudinal outcomes.nnSTUDY RESULTS: Of 319 patients, 240 (75.24%) experienced subthreshold psychotic symptoms indicative of a CHR-P state; of these, 51 (21.25%) had potential BIPS (either alone or with APS) and 189 (78.75%) potential APS only. There were no mean differences in scores for psychotic symptoms, affective symptoms, or functioning between subgroups. However, there was a slower improvement in Global Assessment of Functioning (GAF) scores in the putative APS subgroup, which converged with the putative BIPS subgroup by year 2.nnCONCLUSIONS: Putative CHR-P subcategories of APS and BIPS exhibited similar outcome trajectories beyond psychosis onset, except for a possibly slower functional recovery in the putative APS subgroup. Longer term studies across stages of illness are needed to better understand the prognostic utility of these identifiers after FEP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42418951,

title = {An appraisal of practice guidelines for early intervention services for psychosis: Using AGREE II (Appraisal of Guidelines for Research and Evaluation) to enhance the quality and trustworthiness of guidelines in the future},

author = {Manuela Ferrari and Nicole Pawliuk and Jai Shah and Amal Abdel-Baki and Phil Tibbo and Donald Addington and Marc-André Roy and Ridha Joober and Kevin MacDonald and Srividya N Iyer},

doi = {10.1016/j.schres.2026.06.005},

issn = {1573-2509},

year  = {2026},

date = {2026-07-01},

journal = {Schizophr Res},

volume = {295},

pages = {282--291},

abstract = {BACKGROUND: Early intervention services (EIS) for psychosis have expanded internationally. Yet, the quality of the guidelines to support and monitor them has never been evaluated. We therefore aimed to systematically appraise the quality of EIS guidelines.nnSTUDY DESIGN: We conducted a systematic review of grey literature websites, supplemented by guidelines identified in a prior scoping review. Eligible documents were guidelines focused on/with a section on early intervention or first episode psychosis. Two independent reviewers appraised each guideline using the Appraisal of Guidelines for Research and Evaluation (AGREE II).nnSTUDY RESULTS: Thirty-two guidelines were included. Guidelines varied widely on scores for the AGREE II domains. Many scored high (≥70%) on Scope and Purpose (24/32; 75%) and Clarity of Presentation (22/32; 69%). Only 22% (7/32) scored well on Rigour of Development, primarily due to the lack of methods for evidence identification and appraisal. The lowest scoring domain was Applicability; only two guidelines scored ≥70%, while more than half provided no information on barriers or facilitators to implementation. Stakeholder involvement, especially from service users, was limited in developing EIS-specific guidelines. Guidelines performing consistently well were from large guideline development groups and used established evidence-grading methods.nnCONCLUSIONS: This first systematic appraisal shows that while many EIS guidelines clearly articulate aims and recommendations, substantial methodological and implementation gaps remain. Nonetheless, EIS guidelines score like others in psychiatry. Still, limited stakeholder engagement and applicability may impede consistent, evidence-based EIS delivery. Future guidelines should explicitly describe evidence-based review processes, integrate service user input, and use AGREE II-like tools to enhance their usability and impact.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41992106,

title = {Satisfaction With Youth Mental Health Services in Diverse Settings: Results From a Pan-Canadian Initiative},

author = {John Bedirian and Tovah Cowan and Valérie Noël and Shalini Lal and Ridha Joober and Jai Shah and Amal Abdel-Baki and Rebecca Fuhrer and Patricia Boksa and Neil Andersson and Kathleen MacDonald and Charles-Albert Morin and Mary-Anne Levasseur and Helen Vallianatos and Lacey Augustine and Kevin Friese and Isabelle Godin and Liana Urichuk and Daphne Hutt-MacLeod and Vickie Plourde and Norma Rabbitskin and Paula Reaume-Zimmer and Cécile Rousseau and Ashok Malla and Srividya N Iyer},

doi = {10.1176/appi.ps.20250441},

issn = {1557-9700},

year  = {2026},

date = {2026-04-01},

journal = {Psychiatr Serv},

pages = {appips20250441},

abstract = {OBJECTIVE: Increasing concern about youth mental health has brought interest in service reform. Given the importance of positive care experiences, the authors aimed to study rates of satisfaction, as well as characteristics associated with satisfaction, in ACCESS Open Minds, a cocreated network of enhanced primary and community youth mental health services across Canada.nnMETHODS: A total of 482 youths receiving services at 10 ACCESS Open Minds sites (urban, rural, and Indigenous) completed the Client Satisfaction Questionnaire-4 and responded to additional demographic and service use questions.nnRESULTS: Ninety-one percent of youths were satisfied with their mental health services, substantially higher than the predefined goal of 75%. Youths who preferred virtual services (23%) were less satisfied than those who preferred in-person services.nnCONCLUSIONS: The findings are comparable with those from similar initiatives, highlighting the value of youth-friendly, holistic primary mental health care. High satisfaction across sociodemographic groups and sites suggests that such services are acceptable in diverse communities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42037310,

title = {Increasing Participation of People with Thought Disorder in Clinical Research},

author = {Lena Palaniyappan and Sylvain Baillet and Valentina Bambini and Etienne Barou-Laforie and Marta Bosia and Oli Delgaram-Nejad and Hashwin Ganesh and Ranjini Garani and Neil Harrison and Vegas Hodgins and Ridha Joober and Gina Kuperberg and Tilo Kircher and Chantal Murthy and Susan Rossell and Krish D Singh and Iris E Sommer and Sunny X Tang and Debra Titone and Alban Voppel and Tosh Watson and Irnes Zeljkovic},

doi = {10.1192/j.eurpsy.2026.12211},

issn = {1778-3585},

year  = {2026},

date = {2026-04-01},

journal = {Eur Psychiatry},

pages = {1--36},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41868958,

title = {Exploring the Presenting Problems and Services Received by Youth with Diverse Mental Health Presentations in Integrated Youth Mental Health Services Across Canada},

author = {Sarah Mughal and Alba Sanchez-Allakhverdieva and Amal Abdel-Baki and Neil Andersson and Patricia Boksa and Daphne Hutt-Macleod and Ridha Joober and Shalini Lal and Jessica Chisholm-Nelson and Nora Morrison and Alyssa Frampton and Mary Anne Levasseur and Lacey Augustine and Kevin Friese and Isabelle Godin and Katherine Hay and Norma Rabbitskin and Paula Reaume-Zimmer and Helen Vallianatos and Srividya N Iyer and Ashok Malla and Jai L Shah and },

doi = {10.5334/ijic.10147},

issn = {1568-4156},

year  = {2026},

date = {2026-01-01},

journal = {Int J Integr Care},

volume = {26},

number = {1},

pages = {11},

abstract = {BACKGROUND: Integrated youth mental health (YMH) primary care initiatives have the potential to improve Canada's treatment gap. However, there is no current standard for implementing these services, and offerings vary greatly across models and sites. This has equity implications for the care received by youth with severe presentations.nnMETHODS: We describe the provider-rated problems with which 2995 youth presented to ACCESS Open Minds, a multi-site, Canadian YMH integrated care initiative and the services they received, based on the severity of their needs at intake.nnRESULTS: The largest proportion of youth had both moderate-severe presentations and moderate-to-significant difficulties in functioning (41.67%). The first instance of receiving services following intake for most participants (71.42%) entailed a single service. The highest proportion of youth for whom the type of service received was not documented was those who presented with neither moderate-severe presentations nor poor functioning (15.01%). There was substantial variability in services provided across sites.nnCONCLUSION: Variability in service delivery confirms the need for greater standardization of core service offerings across sites. Future research should assess the appropriateness of services for different presentations to ensure equitable support is provided for all youth.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41124300,

title = {A multisite study of the overlap between symptoms and cognition in schizophrenia: Une étude multicentrique sur le chevauchement entre les symptômes et les troubles cognitifs chez les personnes atteintes de schizophrénie},

author = {Rafal M Skiba and Abhijit M Chinchani and Mahesh Menon and Martin Lepage and Katie M Lavigne and Ashok Malla and Ridha Joober and Joel O Goldberg and R Walter Heinrichs and David J Castle and Amy Burns and Michael W Best and Susan L Rossell and Sebastian Walther and Todd S Woodward},

doi = {10.1177/07067437251387565},

issn = {1497-0015},

year  = {2025},

date = {2025-10-01},

journal = {Can J Psychiatry},

pages = {7067437251387565},

abstract = {ObjectiveCognitive impairment is a core feature of schizophrenia spectrum disorders. Our previous study on a first-episode psychosis cohort showed that symptoms related to impoverished/disorganized communication and motor impoverishment predicted verbal and working memory scores, respectively. This study aimed to explore those predictors in people across the range of illness chronicity.MethodsWe employed iterative Constrained Principal Component Analysis (iCPCA) to investigate the relationship between 15 cognitive measures from the MATRICS battery, including processing speed, attention, working, verbal and nonverbal memory, reasoning, and problem-solving, and 27 Positive and Negative Syndrome Scale (PANSS) items in 198 outpatients from two sites in Australia and one in Canada. The iCPCA method was used to determine symptoms that reliably predict specific combinations of cognitive measures while controlling Type I errors.ResultsWe found that a verbal memory and learning component was predicted by the PANSS item , and a visual attention/working memory component was linked to the PANSS item .ConclusionsThese accord with our previous findings in an early psychosis sample, that is, negative symptoms of diminished expression are key predictors of cognitive abilities in schizophrenia. Namely, communication and motor impoverishments predicted lower scores on tests of verbal memory, learning, visual attention, and working memory. These findings may inform personalized treatment approaches targeting cognitive deficits and negative symptoms in schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40413924,

title = {From resting-state functional hippocampal centrality to functional outcome: An extended neurocognitive model of psychosis},

author = {Jana F Totzek and Jai L Shah and Alexandra L Young and Ashok Malla and Ridha Joober and Delphine Raucher-Chéné and Martin Lepage and Katie M Lavigne},

doi = {10.1016/j.psychres.2025.116538},

issn = {1872-7123},

year  = {2025},

date = {2025-08-01},

journal = {Psychiatry Res},

volume = {350},

pages = {116538},

abstract = {BACKGROUND: We previously proposed a neurocognitive model of psychosis in which reduced morphometric hippocampal-cortical connectivity precedes impaired episodic memory, social cognition, negative symptoms, and functional outcome. We provided support for this model in a patient subtype, and aimed to extend these findings to resting-state functional MRI to potentially explain the progression for a broader range of patients.nnMETHODS: We used a subsample of our previous analysis consisting of 54 patients with first-episode psychosis and 52 controls and applied the machine-learning algorithm Subtype and Stage Inference, which combines clustering and disease progression modeling, to the patient data for rs-functional hippocampal connectivity, episodic memory, social cognition, negative symptoms and functioning.nnRESULTS: We identified three subtypes, with Subtype 0 being unimpaired on the markers, Subtype 1 showing impaired hippocampal connectivity and episodic memory, and Subtype 2 showing impaired memory and a trend for impaired functioning. We identified similar progression patterns to our previously published morphometric results in functional MRI data (hippocampal dysconnectivity preceded cognition, symptoms, and functioning in one subtype and followed these alterations in another subtype). We further show that the impairments in our previously published and current findings across modalities do not necessarily overlap in patients, hinting towards an additive effect of morphometric and resting-state connectivity in explaining the neurocognitive underpinnings of this model.nnCONCLUSION: Our results provide an extension of our previous work and build the foundation for a multimodal neurocognitive model of psychosis, potentially elucidating this aspect of illness progression in psychosis for a broader range of patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39120714,

title = {An intersectional perspective on the sociodemographic and clinical factors influencing the status of not in Education, Employment, or training (NEET) in patients with first-episode psychosis (FEP)},

author = {Jiaxuan Deng and Lisa Sarraf and Adèle Hotte-Meunier and Stéphanie El Asmar and Jai Shah and Ridha Joober and Ashok Malla and Srividya Iyer and Martin Lepage and Geneviève Sauvé},

doi = {10.1007/s00127-024-02732-z},

issn = {1433-9285},

year  = {2025},

date = {2025-06-01},

journal = {Soc Psychiatry Psychiatr Epidemiol},

volume = {60},

number = {6},

pages = {1367--1377},

abstract = {PURPOSE: High rates of Not in Education, Employment or Training (NEET) are seen in people with first episode of psychosis (FEP). Sociodemographic and clinical factors were reported to be associated with NEET status in FEP patients. This study follows Intersectionality to examine the independent and additive effects, and most importantly the intersections of sociodemographic and clinical variables concerning NEET status in FEP patients. It was hypothesized that NEET status in FEP patients would be described by the intersection between at least two predictor variables.nnMETHODS: Secondary analyses with chi-square tests, multiple logistic regression and Chi-squared Automatic Interaction Detection (CHAID) analyses were performed on 440 participants with FEP.nnRESULTS: Chi-square tests indicated that patient socioeconomic status and negative symptom severity were significantly and independently associated with their NEET status. Multiple logistic regression suggested additive effects of age (odds ratio = 1.61), patient socioeconomic status (odds ratio = 1.55) and negative symptom severity (odds ratio = 1.75) in predicting patients' NEET status. CHAID detected an intersection between patients' negative symptom severity and socioeconomic status in shaping their NEET status.nnCONCLUSION: This study explored how the NEET status of patients with FEP was explained not only by the separate effects of negative symptom severity and socioeconomic status but also by the unique intersections of their clinical and social identities. Findings indicated that functional outcomes of patients appear co-constructed by the intersections of multiple identities. Crucial clinical implications of complementing care for negative symptom severity with vocational resources to improve functional outcomes of patients are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40320230,

title = {Longitudinal clinical outcomes based on cognitive and hippocampal clusters of first episode psychosis},

author = {Lucas A Ronat and Delphine Raucher-Chéné and Katie M Lavigne and Mallar Chakravarty and Ridha Joober and Ashok Malla and Jai Shah and Martin Lepage},

doi = {10.1016/j.pnpbp.2025.111392},

issn = {1878-4216},

year  = {2025},

date = {2025-06-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {139},

pages = {111392},

abstract = {BACKGROUND: In first episode psychosis (FEP), cognitive impairments are core features contributing to clinical and functional heterogeneity. Significant impairment indicates greater clinical severity throughout the course of the illness, particularly for negative symptoms. Hippocampal volume is smaller in FEP than in healthy controls (notably subfields like Cornu Ammonis 1-3 and subiculum), and is related to cognitive impairments and negative symptoms. The aim of this study was to compare the clinical and functional trajectories of FEP subgroups as a function of cognitive performance and hippocampal volumes.nnMETHODS: One hundred FEP patients and sixty healthy controls initially assessed using the CogState research battery, underwent 3 T MRI to extract hippocampal subfields and adjacent structures using the MAGeT brain algorithm. Clinical assessments were carried out for negative (Motivational and Pleasure - MAP, and diminished expression - EXP) and depressive symptoms, and global functioning. Measurements were taken at 4 time points (3, 9, 15, 21 months following program entry). Based on available first timepoint standardized cognitive and hippocampal features, using healthy controls as reference, clusters were determined by a hierarchical ascending classification. Their clinical and functional longitudinal trajectories were analyzed using linear mixed-effects models.nnRESULTS: Three baseline clusters were revealed: normal-range hippocampal volume with low attention, working and verbal memory (FEP 0), small hippocampus with low verbal memory and social cognition (FEP 1), and large hippocampus with low verbal memory (FEP 2). At baseline, the clusters did not differ on symptoms severity and global functioning. Longitudinally, MAP, EXP and depressive symptoms decreased over time in FEP 0. Global functioning improved in FEP 0 and FEP 1, while FEP 2 was clinically and functionally stable over time. Longitudinal inter-group comparisons did not yield any significant differences.nnCONCLUSION: The clusters were dissociated between hippocampus and cognition, but their trajectories suggest the importance of hippocampal integrity in the clinical and/or functional outcome. Future studies are needed to understand intervention efficiency depending on hippocampal integrity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40544541,

title = {Implementation of a digital measurement-based care approach in an early intervention service for psychosis: the PEPP-Montreal electronic data capture protocol and its alignment with learning health system principles},

author = {Elissa Zavaglia and Ridha Joober and Srividya N Iyer and Kevin MacDonald and Martin Lepage and Sherezad Abadi and Jai Shah and Manuela Ferrari},

doi = {10.1016/j.schres.2025.05.021},

issn = {1573-2509},

year  = {2025},

date = {2025-06-01},

journal = {Schizophr Res},

volume = {282},

pages = {141--149},

abstract = {Measurement-based care, crucial for improving outcomes in psychiatric disorders, remains underutilized, particularly during the impactful early treatment phases. Inspired by a learning health system approach, a hybrid paper/electronic data capture platform was developed at PEPP-Montreal, an early psychosis program, gathering data on patient socio-demographics, symptoms, functioning, pathways to care, substance use, and medication monitoring. This article evaluates the year-one deployment of this innovative infrastructure (2022-2023). The novel 2022 hybrid infrastructure was compared with the 2016 paper-based version, using the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). Phase 1 identified evidence-based clinical measures including patient-reported, clinician-reported, and evaluator-reported outcomes, while phase 2 further streamlined and implemented the electronic data capture platform. Continuous data collection through the platform was deployed at six time points. Results included: Reach: N = 53/81 patients used paper/electronic data for their year-one service evaluation. Effectiveness: The automated, hybrid paper/electronic protocol optimized data management. Adoption: Rates of electronic patient-reported outcomes were higher in 2022-2023 than 2016-2017 (paper version). Completion rates for clinician-reported outcomes were highest at baseline (year-one). Implementation/maintenance: Barriers and facilitators, essential adaptations, and sustainable impacts were identified. Using electronic, measurement-based data collection accelerates feedback closer to real time and alignment with learning health system principles. Implementing the hybrid data collection platform at PEPP-Montreal provided valuable insights into using measurement-based care to inform quality of services. In the complex transition to a digital protocol within a learning health system, including engagement of key stakeholders, using the hybrid protocol was a necessary first step.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40374762,

title = {Subtyping first-episode psychosis based on longitudinal symptom trajectories using machine learning},

author = {Yanan Liu and Sara Jalali and Ridha Joober and Martin Lepage and Srividya Iyer and Jai Shah and David Benrimoh},

doi = {10.1038/s44184-025-00129-7},

issn = {2731-4251},

year  = {2025},

date = {2025-05-01},

journal = {Npj Ment Health Res},

volume = {4},

number = {1},

pages = {18},

abstract = {Clinical course after first episode psychosis (FEP) is heterogeneous. Subgrouping and predicting longitudinal symptom trajectories after FEP may help develop personalized treatment approaches. We utilized k-means clustering to identify clusters of 411 FEP patients based on longitudinal positive and negative symptoms. Three clusters were identified. Cluster 1 exhibits lower positive and negative symptoms (LS), lower antipsychotic dose, and relatively higher affective psychosis; Cluster 2 shows lower positive symptoms, persistent negative symptoms (LPPN), and intermediate antipsychotic doses; Cluster 3 presents persistently high levels of both positive and negative symptoms (PPNS), and higher antipsychotic doses. We predicted cluster membership (AUC of 0.74) using ridge logistic regression on baseline data. Key predictors included lower levels of apathy, affective flattening, and anhedonia/asociality in the LS cluster, compared to the LPPN cluster. Hallucination severity, positive thought disorder and manic hostility predicted PPNS. These results help parse the FEP trajectory heterogeneity and may facilitate the development of personalized treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40319470,

title = {Latent Trajectories of Positive, Negative Symptoms and Functioning in Early Intervention Services for First-Episode Psychosis: A 2-Year Follow-Up Study},

author = {Olivier Percie du Sert and Joshua Unrau and Manish Dama and Lena Palaniyappan and Jai Shah and Ridha Joober and Delphine Raucher-Chéné and Ashok Malla and Martin Lepage},

doi = {10.1093/schbul/sbaf045},

issn = {1745-1701},

year  = {2025},

date = {2025-05-01},

journal = {Schizophr Bull},

abstract = {BACKGROUND: From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early intervention services (EIS), this study aimed to examine latent trajectories of positive and negative symptoms and functioning among FEP individuals undergoing EIS.nnSTUDY DESIGN: The Prevention and Early Intervention Program for Psychoses (PEPP-Montreal) is a 2-year EIS for FEP that conducted longitudinal assessments of 689 individuals aged 14-35, including sociodemographics, cognition, psychopathology, and functioning. Latent growth mixture modeling was used to identify distinct patterns of clinical and functional trajectories. The inter-relationship between trajectories, and the association of trajectory membership with baseline characteristics and distal outcomes were investigated using the manual 3-step approach.nnSTUDY RESULTS: Two positive symptom trajectories (Stable-low-32%, Fluctuating-68%,), 3 negative symptom trajectories (Decreasing-41%, Fluctuating-15%, and Stable-high-44%), and 2 functioning trajectories (Increasing-57%, Stable-moderate-43%) were identified. Early treatment response, particularly on negative symptoms, consistently and strongly predicted better outcome trajectories (OR = [3.4-5.5]). Trajectories of higher symptom severity were associated with trajectory of worse functioning (RR = [1.5-2.2]), which exhibited lower rates of clinical and functional remission.nnCONCLUSION: These findings offer insights into clinically meaningful subgroups of individuals that could inform the prognosis of FEP and the development of individually tailored EIS. Individuals who do not show early improvement in negative symptoms may benefit from earlier psychosocial interventions specifically targeting actionable factors that contribute to secondary negative symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40015233,

title = {Association of anticholinergic burden with hippocampal subfields volume in first-episode psychosis},

author = {Agnès Belkacem and Katie M Lavigne and Delphine Raucher-Chéné and Carolina Makowski and Mallar Chakravarty and Ridha Joober and Ashok Malla and Jai Shah and Martin Lepage},

doi = {10.1016/j.pscychresns.2025.111968},

issn = {1872-7506},

year  = {2025},

date = {2025-04-01},

journal = {Psychiatry Res Neuroimaging},

volume = {348},

pages = {111968},

abstract = {Polypharmacy is relatively common in early psychosis, but little attention has been paid to the anticholinergic burden of medication use (the cumulative effect of medications that block the cholinergic system). Evidence suggests that anticholinergic burden is associated with cognitive deficits and that hippocampal dysfunction may be involved in those impairments. We aimed to examine this association in a cohort of patients with first-episode psychosis. We hypothesized that patients with the highest burden would experience a more significant reduction in hippocampal volume compared to those with low burden and healthy controls, both at baseline (3 months) and at month 12. Patients (n = 82; low burden [n = 64] and high burden [n = 18], defined by a Drug Burden Index cut-off of 1) followed at the PEPP-Montreal clinic, and controls (n = 55) completed a 3T MRI at both timepoints. After controlling for antipsychotic dosage at both timepoints, results at baseline and over time revealed a greater reduction in left fimbria volumes in high-burden patients compared to low-burden patients and controls. Overall, the associations observed between high anticholinergic burden and hippocampal volume provide further evidence for considering this dimension when prescribing medication in early psychosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39986368,

title = {White matter integrity and verbal memory following a first episode of psychosis: A longitudinal study},

author = {Joseph Ghanem and Jana F Totzek and Charlie Henri-Bellemare and Delphine Raucher-Chéné and Gregory Kiar and Raihaan Patel and M Mallar Chakravarty and Jai L Shah and Ridha Joober and Ashok Malla and Martin Lepage and Katie M Lavigne},

doi = {10.1016/j.pnpbp.2025.111294},

issn = {1878-4216},

year  = {2025},

date = {2025-03-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {137},

pages = {111294},

abstract = {Psychotic disorders are heterogeneous disorders for which there is evidence of structural and functional brain abnormalities. The role of white matter integrity, often measured via Fractional Anisotropy (FA), has played a controversial role in individuals with a first episode of psychosis (FEP). Similarly, some FEP studies have observed that higher FA is associated with better verbal memory, but others failed to find such an association. Studying the early stages of psychosis represents a promising avenue to overcome previous confounding factors and characterize the disease in its early clinical stages. Eighty individuals with a FEP were recruited from a specialized early intervention program for psychosis alongside 55 non-clinical controls from the community matched for age and sex. Both groups were followed and scanned 4 times: at baseline (within 3 months after program entry), 6 months, 12 months, and 18 months. Tract-Based Spatial Statistics (TBSS) were used on 3.0 Tesla diffusion-weighted images to extract fractional anisotropy values for white matter regions of interest in accordance with the John Hopkins University white-matter tractography atlas. The analysis revealed no significant main effect of group or time, and no significant associations between FA and verbal memory. Overall, differences in FA are small early in the course of illness and longer follow-up periods may be required to identify possible changes during a critical intervention window.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39787740,

title = {Exploring delusional themes and other symptoms in first episode psychosis: A network analysis over two timepoints},

author = {Fjolla Berisha and Vincent Paquin and Ian Gold and Bratislav Misic and Lena Palaniyappan and Ashok Malla and Srividya Iyer and Ridha Joober and Martin Lepage and Jai Shah},

doi = {10.1016/j.psychres.2024.116349},

issn = {1872-7123},

year  = {2025},

date = {2025-02-01},

journal = {Psychiatry Res},

volume = {344},

pages = {116349},

abstract = {Delusions are a defining feature of psychosis and play an important role in the conceptualization and diagnosis of psychotic disorders; however, the particular role that different delusions play in the prognosis of these disorders is not well understood. This study explored relationships between delusions and other symptoms in 674 first episode psychosis (FEP) individuals by comparing symptom networks between baseline and 12 months after intake to an early intervention service. Specifically, we (1) estimated regularized partial correlation networks at baseline and month 12, (2) identified the most central symptoms in each network, (3) identified clusters of highly connected symptoms, and (4) compared networks to examine changes in structure and connectivity. At baseline, the most central symptoms were depression, delusions of mind reading, and delusions of thought insertion. At month 12, they were hallucinations, persecutory delusions, and delusions of thought insertion. A symptom cluster was identified at both timepoints comprising of five delusions corresponding to passivity experiences. While network structures did not differ significantly, the month 12 network was significantly more highly connected. Our study captures a shift in illness trajectory over time, wherein transdiagnostic symptomatology at baseline becomes more consolidated around psychotic symptoms by month 12.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40009399,

title = {An Approach to Providing Timely Mental Health Services to Diverse Youth Populations},

author = {Srividya N Iyer and Patricia Boksa and Ridha Joober and Jai Shah and Rebecca Fuhrer and Neil Andersson and Shalini Lal and Giuseppe D'Andrea and Nora Morrison and Valerie Noel and Daniel Rabouin and Tovah Cowan and Kathleen MacDonald and Mary Anne Levasseur and Feodor Poukhovski-Sheremetyev and Amal Abdel-Baki and Lacey Augustine and Kevin Friese and Isabelle Godin and Katherine Hay and Daphne Hutt-MacLeod and Vickie Plourde and Norma Rabbitskin and Paula Reaume-Zimmer and Cécile Rousseau and Heather Rudderham and Adam Abba-Aji and Diane Aubin and Liana Urichuk and Helen Vallianatos and Shirin Golchi and Ina Winkelmann and Jessica Chisholm-Nelson and Ashok Malla},

doi = {10.1001/jamapsychiatry.2024.4880},

issn = {2168-6238},

year  = {2025},

date = {2025-02-01},

journal = {JAMA Psychiatry},

volume = {82},

number = {5},

pages = {470--480},

abstract = {IMPORTANCE: Accessing mental health care is challenging for youths, especially those facing intersectional disadvantages, but whether enhancing youth services increases reach and timeliness has rarely been investigated. ACCESS Open Minds (ACCESS-OM) transformed services at urban, rural, and Indigenous sites in Canada using 5 principles (early identification, rapid access, appropriate care, no age-based transitions from 11-25 years, and youth and family engagement).nnOBJECTIVE: To evaluate whether the number of youths referred (hypothesis 1), offered evaluation appointments within 72 hours of referral (hypothesis 2), and receiving services within 30 days of the first appointment (hypothesis 3) increased over the course of ACCESS-OM's implementation.nnDESIGN, SETTING, AND PARTICIPANTS: This cohort study included youths (aged 11-25 years) at 11 sites referred between March 2016 and December 2020. Data were analyzed from April 2022 to April 2024.nnEXPOSURE: Existing primary and/or community services implemented ACCESS-OM's core components: broad-spectrum mental health services, outreach, youth-friendly walk-in spaces, open systems accepting referrals from multiple sources, and response-time benchmarks (72 hours to evaluation and 30 days to start treatment).nnMAIN OUTCOMES AND MEASURES: Outcomes were the referral rate and the probability of being offered a first evaluation within 72 hours and receiving services within 30 days. Dates of referral and/or help-seeking, first offered appointment, first evaluation, and first services received were recorded. Multilevel negative binomial regression was used for hypothesis 1, and time-to-event analyses followed by multilevel accelerated failure time (AFT) models were used for hypotheses 2 and 3.nnRESULTS: A total of 7889 youths were referred; 4519 (mean [SD] age, 19.3 [3.4] years; 2440 [54%] cisgender women; 1049 [23.21%] Indigenous; 991 [21.93%] Visible Minority [Arab, Black, Chinese, Filipino, Japanese, Korean, Latin American, South Asian, Southeast Asian, West Asian, other ethnicity, and multiple ethnicities]; and 1525 [49.10%] White) were evaluated before March 2020. Each 6-month progression after implementation was associated with a 10% increase in referral rates (IRR, 1.10; 95% CI, 1.07-1.13). The probability of being offered an initial appointment (χ22 = 20.30; P < .001) and receiving services (χ22 = 4.48; P = .01) after any given delay differed significantly over the 3 years. In adjusted AFT models, each 6-month progression was associated with a 3% decrease in time to offered evaluation (time ratio [TR], 0.97; 95% CI, 0.95-0.99) and first services (TR, 0.97; 95% CI, 0.94-1.00). Moderate to severe mental health problems were associated with longer delays to offered first appointments (TR, 1.14; 95% CI, 1.06-1.24) and services (TR, 1.11; 95% CI, 1.01-1.22).nnCONCLUSIONS AND RELEVANCE: As hypothesized, after ACCESS-OM implementation, more youths sought help, and the timeliness of initial response and services improved over time. These findings suggest that core principles, benchmarks, and implementation supports are valuable in organizing youth mental health care. Future efforts should make benefits equitable for those with severe problems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39467482,

title = {Acceptability, engagement, and efficacy of cognitive remediation for cognitive outcomes in young adults with first-episode psychosis and social anxiety: A randomized-controlled trial},

author = {Elisabeth Thibaudeau and Christopher R Bowie and Tina Montreuil and Larry Baer and Tania Lecomte and Ridha Joober and Amal Abdel-Baki and G Eric Jarvis and Howard C Margolese and Luigi De Benedictis and Norbert Schmitz and Ashok K Malla and Martin Lepage},

doi = {10.1016/j.psychres.2024.116243},

issn = {1872-7123},

year  = {2024},

date = {2024-12-01},

journal = {Psychiatry Res},

volume = {342},

pages = {116243},

abstract = {Social anxiety disorder (SAD) is a frequent comorbidity in first-episode psychosis (FEP) and may increase cognitive impairments. Cognitive remediation (CR) is an effective treatment for cognition, particularly in a group format. This study aims to assess the efficacy, acceptability and engagement of group CR on cognitive outcomes in FEP+SAD compared to group cognitive-behavioral therapy (CBT). Participants with FEP+SAD were randomized to group CR (n = 45) or CBT-SAD (n = 51). They were assessed for cognition at baseline, post-therapy and 3- and 6-month follow-up. The CR group additionally completed scale to assess perceived competency and enjoyment in CR. Linear mixed models for repeated measures were used for cognitive scores. Descriptive statistics and t-tests were used to summarize acceptability, perceived competency, and enjoyment, for CR completers and non-completers. The CR group performed significantly better than CBT on executive functions and visual memory at post-therapy compared to baseline. Twenty participants completed CR (44 %; mean 5.5 sessions). At week 1, CR non-completers presented higher levels of perceived competency. Completers reported higher enjoyment scores at the last session compared to the first session. Group CR is effective for cognitive outcomes in FEP+SAD, but acceptability and engagement present a challenge. Future studies are necessary to explore approaches promoting engagement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39205914,

title = {Adjunctive methylphenidate extended release in patients with schizophrenia: Protocol of a single-centre fixed dose cross-over open-label trial to improve functional and cognitive outcomes},

author = {Naista Zhand and David Attwood and Alain Labelle and Ridha Joober and Carrie Robertson and Philip D Harvey},

doi = {10.1016/j.conctc.2024.101337},

issn = {2451-8654},

year  = {2024},

date = {2024-10-01},

journal = {Contemp Clin Trials Commun},

volume = {41},

pages = {101337},

abstract = {BACKGROUND: Cognitive symptoms, among the core symptoms of schizophrenia, are associated with poor functional outcome and burden of illness. To date, there is no effective pharmacological treatment for these symptom clusters. Augmentation with psychostimulants has been proposed as a potential treatment option.nnOBJECTIVES: The present study aims to assess off-label use of adjunctive methylphenidate extended release (ER) in patients with schizophrenia who are stable on antipsychotic medications, and to assess its efficacy on functioning and cognitive outcome.nnMETHODS: This is a single centre study at the Royal Ottawa Mental Health Centre. An open-label fixed dose controlled cross-over trial is planned. Eligible participants will be randomized into one of two arms of the study: 1) four weeks of add-on methylphenidate ER 36 mg, or 2) four weeks of treatment as usual. At 4 weeks, participants will switch arms. The duration of the study includes 8 weeks of treatment and a follow-up visit at 12 weeks. Primary outcome measures include tablet-based tests of functioning and cognition (VRFCAT and BAC) and will be administered at baseline and every 4 weeks. We are aiming to recruit a total of 24 participants.nnEXPECTED OUTCOMES: The proposed project intends to assess a potential treatment option for cognitive deficits of schizophrenia, for which there are no recommendations by current treatment guidelines. The novelty and significance of the current study is that it investigates this intervention and assess applicability of it in a "real world setting" in a tertiary care hospital.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38605172,

title = {Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome},

author = {Jana F Totzek and M Mallar Chakravarty and Ridha Joober and Ashok Malla and Jai L Shah and Delphine Raucher-Chéné and Alexandra L Young and Dennis Hernaus and Martin Lepage and Katie M Lavigne},

doi = {10.1038/s41380-024-02549-x},

issn = {1476-5578},

year  = {2024},

date = {2024-10-01},

journal = {Mol Psychiatry},

volume = {29},

number = {10},

pages = {2929--2938},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}