The Toronto Adolescent and Youth Cohort Study: Study Design and Early Data Related to Psychosis Spectrum Symptoms, Functioning, and Suicidality.

BACKGROUND: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality. METHODS: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data. RESULTS: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs. CONCLUSIONS: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality.

Neuroimaging and Biosample Collection in the Toronto Adolescent and Youth Cohort Study: Rationale, Methods, and Early Data.

BACKGROUND: The Toronto Adolescent and Youth (TAY) Cohort Study will characterize the neurobiological trajectories of psychosis spectrum symptoms, functioning, and suicidality (i.e., suicidal thoughts and behaviors) in youth seeking mental health care. Here, we present the neuroimaging and biosample component of the protocol. We also present feasibility and quality control metrics for the baseline sample collected thus far. METHODS: The current study includes youths (ages 11-24 years) who were referred to child and youth mental health services within a large tertiary care center in Toronto, Ontario, Canada, with target recruitment of 1500 participants. Participants were offered the opportunity to provide any or all of the following: 1) 1-hour magnetic resonance imaging (MRI) scan (electroencephalography if ineligible for or declined MRI), 2) blood sample for genomic and proteomic data (or saliva if blood collection was declined or not feasible) and urine sample, and 3) heart rate recording to assess respiratory sinus arrhythmia. RESULTS: Of the first 417 participants who consented to participate between May 4, 2021, and February 2, 2023, 412 agreed to participate in the imaging and biosample protocol. Of these, 334 completed imaging, 341 provided a biosample, 338 completed respiratory sinus arrhythmia, and 316 completed all 3. Following quality control, data usability was high (MRI: T1-weighted 99%, diffusion-weighted imaging 99%, arterial spin labeling 90%, resting-state functional MRI 95%, task functional MRI 90%; electroencephalography: 83%; respiratory sinus arrhythmia: 99%). CONCLUSIONS: The high consent rates, good completion rates, and high data usability reported here demonstrate the feasibility of collecting and using brain imaging and biosamples in a large clinical cohort of youths seeking mental health care.

Cognition and Educational Achievement in the Toronto Adolescent and Youth Cohort Study: Rationale, Methods, and Early Data.

BACKGROUND: Both cognition and educational achievement in youths are linked to psychosis risk. One major aim of the Toronto Adolescent and Youth (TAY) Cohort Study is to characterize how cognitive and educational achievement trajectories inform the course of psychosis spectrum symptoms (PSSs), functioning, and suicidality. Here, we describe the protocol for the cognitive and educational data and early baseline data. METHODS: The cognitive assessment design is consistent with youth population cohort studies, including the NIH Toolbox, Rey Auditory Verbal Learning Test, Wechsler Matrix Reasoning Task, and Little Man Task. Participants complete an educational achievement questionnaire, and report cards are requested. Completion rates, descriptive data, and differences across PSS status are reported for the first participants (N = 417) ages 11 to 24 years, who were recruited between May 4, 2021, and February 2, 2023. RESULTS: Nearly 84% of the sample completed cognitive testing, and 88.2% completed the educational questionnaire, whereas report cards were collected for only 40.3%. Modifications to workflows were implemented to improve data collection. Participants who met criteria for PSSs demonstrated lower performance than those who did not on numerous key cognitive indices (p < .05) and also had more academic/educational problems. CONCLUSIONS: Following youths longitudinally enabled trajectory mapping and prediction based on cognitive and educational performance in relation to PSSs in treatment-seeking youths. Youths with PSSs had lower cognitive performance and worse educational outcomes than youths without PSSs. Results show the feasibility of collecting data on cognitive and educational outcomes in a cohort of youths seeking treatment related to mental illness and substance use.

The quick pivot: Capturing real world modifications for the re-implementation of an early psychosis program transitioning to virtual delivery.

Background: Team-based Early Psychosis Intervention (EPI) services is standard of care for youth with psychosis. The COVID-19 pandemic required most EPI services to mount an unplanned, rapid pivot to virtual delivery, with limited guidance on how to deliver virtual clinical services or whether quality of re-implementation and treatment outcomes would be impacted. We used a structured approach to identify essential modifications for the delivery of core components and explored facilitators and barriers for re-implementation and fidelity of a virtually delivered EPI intervention. Materials and methods: NAVIGATE is a structured approach to team-based EPI. It provides detailed modules to guide delivery of core components including medication management, psychoeducation and psychotherapies, supported employment/education, and family education. Having initially implemented NAVIGATE at the Centre for Addiction and Mental Health (CAMH) in 2017, the EPI service transitioned to virtual delivery amid the COVID pandemic. Using a practice profile developed to support implementation, we detailed how core components of NAVIGATE were rapidly modified for virtual delivery as reported in structured group meetings with clinicians. The Framework for Reporting Adaptations and Modifications for Evidence-Based Interventions (FRAME) was used to describe modifications. Fidelity to the EPI standards of care was assessed by the First Episode Psychosis Fidelity Scale (FEPS-FS). Re-implementation barriers and facilitators and subsequent mitigation strategies were explored using structured clinician interviews guided by the Consolidated Framework for Implementation Research (CFIR). Results: Identified modifications related to the intervention process, context, and training. We identified contextual factors affecting the re-implementation of virtually delivered NAVIGATE and then documented mitigating strategies that addressed these barriers. Findings can inform the implementation of virtual EPI services elsewhere, including guidance on processes, training and technology, and approaches to providing care virtually. Discussion: This study identified modifications, impacts and mitigations to barriers emerging from rapid, unplanned virtual delivery of EPI services. These findings can support delivery of high-quality virtual services to youth with psychosis when virtual care is indicated.

A normative chart for cognitive development in a genetically selected population.

Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.

Adapting Evidence-Based Early Psychosis Intervention Services for Virtual Delivery: Protocol for a Pragmatic Mixed Methods Implementation and Evaluation Study.

BACKGROUND: Timely and comprehensive treatment in the form of early psychosis intervention (EPI) has become the standard of care for youth with psychosis. While EPI services were designed to be delivered in person, the COVID-19 pandemic required many EPI programs to rapidly transition to virtual delivery, with little evidence to guide intervention adaptations or to support the effectiveness and satisfaction with virtual EPI services. OBJECTIVE: This study aims to explore the adaptations required to deliver NAVIGATE, a model of coordinated specialty care used in EPI, in a virtual format. This study will evaluate implementation of the NAVIGATE model delivered virtually by describing the nature of the adaptations to the intervention, assessing fidelity to the EPI model and the satisfaction of clients, family members, and care providers. We will investigate barriers and facilitators to virtual NAVIGATE implementation, service engagement, and health equity impacts of this work. METHODS: The Centre for Addiction and Mental Health (Toronto, Ontario, Canada) transitioned to delivering NAVIGATE virtually early in the COVID-19 pandemic. The Framework for Reporting Adaptations and Modifications for Evidence-Based Interventions will be used to describe the adaptations required to deliver NAVIGATE virtually. Fidelity to the EPI model will be measured using the First Episode Psychosis Services Fidelity Scale and fidelity to NAVIGATE will be assessed by investigating adherence to its core components. Implementation facilitators and barriers will be explored using semistructured interviews with providers informed by the Consolidated Framework for Implementation Research. Satisfaction with virtually delivered NAVIGATE will be assessed with virtual client and provider experience surveys and qualitative interviews with clients, family members, and providers. Service engagement data will be collected through review of medical records, and potential impacts of virtually delivered NAVIGATE on different population groups will be assessed with the Health Equity Impact Assessment. RESULTS: Virtual clinical delivery of NAVIGATE started in March 2020 with additional adaptations and data collection is ongoing. Data will be analyzed using descriptive statistics and survival analysis for quantitative data. Qualitative data will be analyzed using thematic content analysis. Integration of qualitative and quantitative data will occur at the data collection, interpretation, and reporting levels following a convergent design. CONCLUSIONS: This study will provide information regarding the type of intervention adaptations required for virtual delivery of NAVIGATE for youth with early psychosis, ensuring access to high-quality care for this population during the pandemic and beyond by guiding future implementation in similar contexts. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34591.

Mortality After the First Diagnosis of Schizophrenia-Spectrum Disorders: A Population-based Retrospective Cohort Study.

There is emerging evidence of high mortality rates after the first diagnosis of psychotic disorder. The objective of this study was to estimate the standardized mortality ratio (SMR) in a population-based cohort of individuals with a first diagnosis of schizophrenia-spectrum psychotic disorder (SSD). The cohort included a population-based sample of individuals with a first diagnosis of SSD based on the first diagnosis occurring during hospitalization or in an outpatient setting between 2007 and 2010 in Ontario, Canada. All patients were followed for 5 years after the first diagnosis. The primary outcome was SMR, including all-cause, suicide-related, accidental, and other causes. Between 2007 and 2010, there were 2382 patients in the hospitalization cohort and 11 003 patients in the outpatient cohort. Over the 5-year observation period, 97 (4.1%) of the hospitalization cohort and 292 (2.7%) of the outpatient cohort died, resulting in an SMR of 13.6 and 9.1, respectively. In both cohorts, suicide was the most common cause of death. Approximately 1 in 25 patients with a first diagnosis of SSD during hospitalization, and 1 in 40 patients with a first diagnosis of SSD in an outpatient setting, died within 5 years of first diagnosis in Ontario, Canada. This mortality rate is between 9 and 13 times higher than would be expected in the age-matched general population. Based on these data, timely access to services should be a public health priority to reduce mortality following a first diagnosis of an SSD.

The Dutch Bipolar Offspring Study: Cognitive Development and Psychopathology.

Various aspects of the relationship between cognitive impairment and bipolar disorder are not clear yet. This study examines cognitive and educational functioning prospectively in offspring at familial risk for bipolar disorder, in order to improve our understanding of the association between cognitive functioning and psychopathology. Bipolar offspring (N = 92) from the prospective Dutch bipolar offspring study were evaluated at adolescence and adulthood for IQ estimate, educational achievement and development of any psychiatric disorder. The main outcome was IQ estimate after 12 years of follow-up (offspring mean age 28 years). Generalized estimating equation (GEE) analyses showed that any lifetime DSM-IV axis I diagnosis was related to a lower cognitive outcome at adulthood as compared to unaffected bipolar offspring. No specific association was found for type of diagnosis. Early onset psychopathology (diagnosis at or before age 15 years) was significantly related to lower IQ estimate at adulthood, indicating a sensitive period for neurocognitive development.

Educational Level, Underachievement, and General Mental Health Problems in 10,866 Adolescents.

OBJECTIVE: Previous research suggests that cognitive functioning is associated with the risk of several adult psychiatric disorders. In this study we investigated whether adolescents who perform worse than expected at secondary school are at a higher risk for general mental health problems. METHODS: In a cross-sectional survey comprising 10,866 Dutch adolescents aged 13 to 16 years, underachievement at secondary school was defined as the discrepancy between predicted school grade and actual grade 1 or 3 years later. Mental health problems were assessed using the Strengths and Difficulties Questionnaire. We investigated the association of underachievement with mental health problems using logistic regression, adjusting for potential confounders. RESULTS: Underachievement was associated with general psychopathology in pupils aged 13 to 14 years (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.47-2.37) and in pupils aged 15 to 16 years (OR, 2.05; 95% CI, 1.67-2.52) in a multivariate analysis including sociodemographic factors. The association between underachievement and mental health problems was attenuated when school factors such as teacher advice and interaction between underachievement and teacher advice were added, but underachievement remained significantly associated with mental health problems in adolescents in the higher educational tracks (pupils aged 13-14 years: OR, 2.22; 95% CI, 1.07-4.60 and OR, 2.41; 95% CI, 1.10-5.30, age 15-16 years: OR, 2.63; 95% CI, 1.38-5.03). In the multivariate analysis including the interaction between underachievement and teacher advice, a significant interaction effect occurs between underachievement and teacher advice in the higher tracks. Values of OR and CI are given for each significant interaction term. In the younger age group (pupils aged 13-14 years) this results in 2 sets of OR and CI. This association was most pronounced for the hyperactivity subscale of the Strengths and Difficulties Questionnaire. CONCLUSIONS: Underachievement at secondary school is associated with general mental health problems, especially with hyperactivity symptoms, in pupils who started at high educational tracks.

Delayed school progression and mental health problems in adolescence: a population-based study in 10,803 adolescents.

BACKGROUND: Accumulating evidence suggests that several adult mental disorders, particularly psychoses, are preceded by impairments in cognitive function, reflected in scholastic underachievement. This study investigates the association between scholastic underachievement and general mental health problems in adolescence, using delay in school progression as a marker of poor scholastic performance. METHOD: Cross-sectional secondary school survey comprising 10,803 adolescents. Participants completed the Strengths and Difficulties Questionnaire (SDQ) to assess mental health problems. The association of delayed school progression with the SDQ was investigated using logistic regression with SDQ as outcome and delayed school progression as primary exposure of interest while adjusting for socio-demographic characteristics, adverse life events, school-related factors, risk taking behaviour, healthy lifestyle and physical health. RESULTS: Unadjusted analysis showed an association between delayed school progression and total mental health problems (OR 1.83, 95% CI 1.27-2.63) in adolescents. After adjusting for other risk factors (socio-demographic factors and life events) in a logistic regression model the association between delayed school progression en mental health problems was attenuated (OR 1.33, 95% CI 0.86-2.05). CONCLUSION: Delayed school progression is associated with general mental health problems in adolescence, but this relationship is heavily confounded by other factors. A causal relationship between impaired cognitive function such as poor scholastic performance and general mental health at adolescence is less likely and delayed school progression may merely be considered an indicator of risk for mental health problems.

Perceived school safety is strongly associated with adolescent mental health problems.

School environment is an important determinant of psychosocial function and may also be related to mental health. We therefore investigated whether perceived school safety, a simple measure of this environment, is related to mental health problems. In a population-based sample of 11,130 secondary school students, we analysed the relationship of perceived school safety with mental health problems using multiple logistic regression analyses to adjust for potential confounders. Mental health problems were defined using the clinical cut-off of the self-reported Strengths and Difficulties Questionnaire. School safety showed an exposure-response relationship with mental health problems after adjustment for confounders. Odds ratios increased from 2.48 ("sometimes unsafe") to 8.05 ("very often unsafe"). The association was strongest in girls and young and middle-aged adolescents. Irrespective of the causal background of this association, school safety deserves attention either as a risk factor or as an indicator of mental health problems.