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

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

Genetic and phenotypic similarity across major psychiatric disorders: a systematic review and quantitative assessment.

There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.

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

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

Speech markers to predict and prevent recurrent episodes of psychosis: A narrative overview and emerging opportunities.

Preventing relapse in schizophrenia improves long-term health outcomes. Repeated episodes of psychotic symptoms shape the trajectory of this illness and can be a detriment to functional recovery. Despite early intervention programs, high relapse rates persist, calling for alternative approaches in relapse prevention. Predicting imminent relapse at an individual level is critical for effective intervention. While clinical profiles are often used to foresee relapse, they lack the specificity and sensitivity needed for timely prediction. Here, we review the use of speech through Natural Language Processing (NLP) to predict a recurrent psychotic episode. Recent advancements in NLP of speech have shown the ability to detect linguistic markers related to thought disorder and other language disruptions within 2-4 weeks preceding a relapse. This approach has shown to be able to capture individual speech patterns, showing promise in its use as a prediction tool. We outline current developments in remote monitoring for psychotic relapses, discuss the challenges and limitations and present the speech-NLP based approach as an alternative to detect relapses with sufficient accuracy, construct validity and lead time to generate clinical actions towards prevention.

The effects of intranasal oxytocin on the efficacy of psychotherapy for major depressive disorder: a pilot randomized controlled trial.

BACKGROUND: Although both pharmacotherapy and psychological treatments are considered to be efficacious in the treatment of major depressive disorder (MDD), one third of patients do not respond to treatment and many experience residual symptoms post-treatment. In this double-blind placebo-controlled randomized control trial (RCT), we assessed whether intranasal oxytocin (OT) augments the therapeutic efficacy of psychotherapy for MDD and improves the therapeutic alliance. METHODS: Twenty-three volunteers (12 female) with MDD underwent 16 sessions of interpersonal therapy. Prior to each session, volunteers self-administered 24 International Units of intranasal OT (n = 12; Syntocinon) or placebo (n = 11). Depressive symptoms were assessed with the Inventory of Depressive Symptomatology at pre- and post-treatment, and at a six month follow-up. RESULTS: Multilevel modeling found a significant effect of OT on the negative slope of depressive symptoms over time (p < 0.05), with medium-large effect sizes at post-treatment (Cohen's d = 0.75) and follow-up (Cohen's d = 0.82). Drug intervention also predicted the intercept when examining the weekly ratings of the therapeutic alliance (p < 0.05), such that volunteers receiving OT, relative to placebo, reported improved therapeutic alliance at session 1. The agreement of goals between therapists and participants, a facet of the therapeutic alliance, mediated the relationship between drug intervention and clinical outcome. CONCLUSION: In this pilot study, the administration of intranasal OT, relative to placebo, improved the therapeutic alliance at the beginning of therapy and therapeutic efficacy of psychotherapy in persons with MDD. Future RCTs should attempt to replicate these findings in larger samples with different therapeutic modalities (ClinicalTrials.gov: NCT02405715).

Maternal smoking during pregnancy and cortical structure in children with attention-deficit/hyperactivity disorder.

Maternal smoking during pregnancy (MSDP) is considered a risk factor for ADHD. While the mechanisms underlying this association are not well understood, MSDP may impact the developing brain in ways that lead to ADHD. Here, we investigated the effect of prenatal smoking exposure on cortical brain structures in children with ADHD using two methods of assessing prenatal exposure: maternal recall and epigenetic typing. Exposure groups were defined according to: (1) maternal recall (+MSDP: n = 24; -MSDP: n = 85) and (2) epigenetic markers (EM) (+EM: n = 14 -EM: n = 21). CIVET-1.1.12 and RMINC were used to acquire cortical brain measurements and perform statistical analyses, respectively. The vertex with highest significance was tested for association with Continuous Performance Test (CPT) dimensions. While no differences of brain structures were identified between +MSDP and -MSDP, +EM children (n = 10) had significantly smaller surface area in the right orbitofrontal cortex (ROFc), middle temporal cortex (RTc) and parahippocampal gyrus (RPHg) (15% FDR) compared to -EM children (n = 20). Cortical surface area in the RPHg significantly correlated with CPT commission errors T-scores. This study suggests that molecular markers may better define exposure to environmental risks, as compared to human recall.

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

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

Treatment with psychostimulants and atomoxetine in people with psychotic disorders: reassessing the risk of clinical deterioration in a real-world setting.

BACKGROUND: Although attention-deficit hyperactivity disorder (ADHD) is often comorbid with schizophrenia spectrum and other psychotic disorders (SZSPD), concerns about an increased risk of psychotic events have limited its treatment with either psychostimulants or atomoxetine. AIMS: To examine whether the risk of hospital admission for psychosis in people with SZSPD was increased during the year following the introduction of such medications compared with the year before. METHOD: This was a retrospective cohort study using Quebec (Canada) administrative health registries, including all Quebec residents with a public prescription drug insurance plan and a diagnosis of psychotic disorder, defined by relevant ICD-9 or ICD-10 codes, who initiated either methylphenidate, amphetamines or atomoxetine, between January 2010 and December 2016, in combination with antipsychotic medication. The primary outcome was time to hospital admission for psychosis within 1 year of initiation. State sequence analysis was also used to visualise admission trajectories for psychosis in the year following initiation of these medications, compared with the previous year. RESULTS: Out of 2219 individuals, 1589 (71.6%) initiated methylphenidate, 339 (15.3%) amphetamines and 291 (13.1%) atomoxetine during the study period. After adjustment, the risk of hospital admission for psychosis was decreased during the 12 months following the introduction of these medications when used in combination with antipsychotics (adjusted HR = 0.36, 95% CI 0.24-0.54; P < 0.0001). CONCLUSIONS: These findings suggest that, in a real-world setting, when used concurrently with antipsychotic medication, methylphenidate, amphetamines and atomoxetine may be safer than generally believed in individuals with psychotic disorders.

Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review.

BACKGROUND: Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well-being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. METHODS: We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. RESULTS: Fifty-eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. CONCLUSIONS: Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

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

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

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

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

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

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

Correlation of the methylomic signature of smoking during pregnancy with clinical traits in ADHD.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD. METHODS: We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively. RESULTS: Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in RUNX1 were positively correlated with the CBCL scores, and DNA methylation in MYO1G correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in GFI1 correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of RUNX1 methylation levels with the CBCL score. LIMITATIONS: The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models. CONCLUSION: This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy.

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

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

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

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

Experiences of a Digital Mental Health Intervention from the Perspectives of Young People Recovering from First-Episode Psychosis: A Focus Group Study.

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.