Pharmacogenetics‐predicted drug metabolism may not match clinically observed metabolism due to a phenomenon known as phenoconversion. Phenoconversion can occur when an inhibitor or inducer of a drug‐metabolizing enzyme is present. Although estimates of phenoconversion in adult populations are available, prevalence estimates in youth populations are limited. To address this gap, we estimated the prevalence of phenoconversion in 1281 youth (6–24 years) receiving pharmacotherapy for mental health conditions and who had pharmacogenetics testing completed for four genes (CYP2B6, CYP2C19, CYP2D6, CYP3A4). Self‐reported medication and cannabidiol/cannabis use were collected at the time of pharmacogenetics testing. Nearly, half (46%) of the cohort was estimated to be phenoconverted for one of the four genes examined. Comparison of metabolizer phenotype frequencies before and after adjustment for phenoconversion showed significantly more youth had actionable phenotypes for CYP2C19 (60.3% vs. 69.1%; P =< 0.001), CYP2D6 (49.3% vs. 63.0%; P =< 0.001), and CYP3A4 (8.5% vs.12.2%; P = 0.003) after phenoconversion adjustment. Of youth who were phenoconverted, 24% had a change in their metabolizer phenotype that would lead to current pharmacogenetics‐based prescribing guidelines recommending a change to standard prescribing (dose adjustment, alternative medication). Our findings indicate a high prevalence of cytochrome P450 phenoconversion among youth receiving pharmacotherapy for mental health conditions. Adjustment for phenoconversion should be considered when implementing pharmacogenetics testing in youth populations to improve the clinical utility of this testing in practice.

Resilience has been championed as important for mitigating stressors and challenges experienced by students during post-secondary education, as evidenced by the abundance of programs aimed at enhancing student resilience. Despite growing attention to resilience, there continues to be a lack of consensus about the definition or operationalization of the concept. Even less is known about how to foster resilience in the post-secondary context, especially for marginalized or underrepresented students, who are recognized to be at increased risk for negative mental health outcomes during their post-secondary education. To address these gaps, we employed qualitative methodology to explore marginalized or underrepresented students’ perceptions of resilience. Findings demonstrated that resilience arises from a complex and dynamic interplay between personal skills and attitudes and resources available within students’ communities. Post-secondary institutions are called to shift from individual student responsibility to a collective and shared responsibility for students’ wellbeing in the face of adversity.

Background: Mental illness among emerging adults is often difficult to ameliorate due to fluctuating symptoms and heterogeneity. Recently, innovative approaches have been developed to improve mental health care for emerging adults, including (1) implementing patient-reported outcome measures (PROMs) to assess illness severity and inform stratified care to assign emerging adults to a treatment modality commensurate with their level of impairment and (2) implementing a rapid learning health system in which data are continuously collected and analyzed to generate new insights, which are then translated to clinical practice, including collaboration among clients, health care providers, and researchers to co-design and coevaluate assessment and treatment strategies. Objective: The aim of the study is to determine the feasibility and acceptability of implementing a rapid learning health system to enable a measurement-based, stratified care treatment strategy for emerging adults. Methods: This study takes place at a specialty clinic serving emerging adults (age 16-24 years) in Calgary, Canada, and involves extensive collaboration among researchers, providers, and youth. The study design includes six phases: (1) developing a transdiagnostic platform for PROMs, (2) designing an initial stratified care model, (3) combining the implementation of PROMs with stratified care, (4) evaluating outcomes and disseminating results, (5) modification of stratified care based on data derived from PROMs, and (6) spread and scale to new sites. Qualitative and quantitative feedback will be collected from health care providers and youth throughout the implementation process. These data will be analyzed at regular intervals and used to modify the way future services are delivered. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework is used to organize and evaluate implementation according to 3 key objectives: improving treatment selection, reducing average wait time and treatment duration, and increasing the value of services. Results: This project was funded through a program grant running from 2021 to 2026. Ethics approval for this study was received in February 2023. Presently, we have developed a system of PROMs and organized clinical services into strata of care. We will soon begin using PROMs to assign clients to a stratum of care and using feedback from youth and clinicians to understand how to improve experiences and outcomes. Conclusions: This study has key implications for researchers and clinicians looking to understand how to customize emerging adult mental health services to improve the quality of care and satisfaction with care. This study has significant implications for mental health care systems as part of a movement toward value-based health care. International Registered Report Identifier (IRRID): PRR1-10.2196/51667

Concerns about the applicability of pharmacogenetic (PGx) testing across diverse ancestry groups have risen from the underrepresentation of non‐European populations in PGx research. Current PGx panels may fail to detect relevant variants in non‐European populations, increasing the likelihood of false‐negative results. To investigate this, we assessed reference allele (*1) and genotype (*1/*1) frequencies by self‐reported ancestry in a cohort of 1086 youth aged 6–24 years who underwent PGx testing. Testing included 10 pharmacogenes (CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, CYP3A5, NUDT15, SLCO1B1, TPMT, and VKORC1) using a panel covering all Association for Molecular Pathology Tier 1 alleles and 53% of Tier 2 alleles. Compared with Europeans (n = 727), non‐Europeans (n = 359) had higher *1 allele frequencies for CYP2C9, CYP2D6, and CYP3A5 (all P < 0.01), while Europeans had higher frequencies for CYP2C19 and VKORC1 (all P < 0.01). Similarly, *1/*1 genotype frequencies were higher in non‐Europeans for CYP2C9 and CYP3A4 (all P < 0.01), but higher in Europeans for VKORC1 (P < 0.01). False‐negative estimates exceeded 1% for CYP2B6, CYP2D6, CYP2C9, CYP2C19, and SLCO1B1 in at least one ancestry group. These findings support the notion that *1 allele and *1/*1 genotype frequencies are more frequent in non‐Europeans for specific genes, but Europeans are also at comparable risk for false‐negative results. Expanded allele coverage on PGx panels could mitigate false‐negative risks, improving equity in PGx testing across diverse populations.

Sertraline is commonly used to treat mental health conditions in youth. However, its tolerability and efficacy vary between individuals, partly due to interindividual differences in drug metabolism. This study assessed the individual and combined impact of genetic variation in cytochrome P450 drug‐metabolizing enzymes on patient‐reported side effects and symptom improvement in 347 youth, aged 6–24, receiving sertraline treatment. Participants reported sertraline dose, duration, adherence, concomitant medications, side effects, and symptom improvement. DNA was extracted from saliva samples and genotyped for CYP2B6 , CYP2C9 , CYP2C19 , CYP2D6 , and CYP3A4 . Individual activity scores and a weighted combinatorial CYP450 activity score were created. Binomial logistic regression models were used to assess the impact individual and combined CYP450 activity scores had on patient‐reported side effects and symptom improvement, both with and without correction for phenoconversion. After adjusting for phenoconversion, other CYP450 activity scores, and covariates, higher activity scores for CYP2D6 (OR = 0.288, 95% CI = 0.091–0.913) and CYP3A4 (OR = 0.002, 95% CI = 0.001–0.375) were nominally associated with reduced odds of symptom improvement. A higher combined CYP450 activity score was associated with reduced odds of symptom improvement (OR = 0.060, 95% CI = 0.004–0.797) and side effects (OR = 0.097, 95% CI = 0.010–0.925). These findings suggest that a combined CYP450 activity score may serve as a marker of symptom improvement and side effects in youth, but validation using sertraline/desmethylsertraline concentrations is required. If validated, these results may inform updates to pharmacogenetic prescribing guidelines for sertraline and support more personalized sertraline use in youth.