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BackgroundDeveloping a digital health innovation can require a substantial amount of financial and human resource investment before it can be scaled for implementation across geographical, cultural, and health care contexts. As such, there is an increased interest in leveraging eHealth innovations developed and tested in one country or jurisdiction and using these innovations in local settings. However, limited knowledge exists on the processes needed to appropriately adapt digital health innovations to optimize their transferability across geographical, cultural, and contextual settings. ObjectiveWe report on the results of an adaptation study of Horyzons, a digital health innovation originally developed and tested in Australia. Horyzons is designed to prevent relapses and support recovery in young people receiving services for first-episode psychosis (FEP). The aim of this study is to assess the initial acceptability of Horyzons and adapt it in preparation for pilot testing in Canada. MethodsThis research took place in 2 specialized early intervention clinics for FEP, located in 1 urban and 1 urban-rural setting, in 2 Canadian provinces. A total of 26 participants were recruited: 15 clinicians (age range 26-56 years) and 11 patients (age range 19-37 years). Following the digital health adaptation framework developed by our team, we used a mixed methods approach, combining descriptive quantitative and qualitative methods across 3 stages of data collection (focus groups, interviews, and consultations), analysis, and adaptations. ResultsOverall, patients and clinicians appreciated the strengths-based approach and social media features of Horyzons. However, participants expressed concerns related to implementation, especially in relation to capacity (eg, site moderation, crisis management, internet speed in rural locations). They also provided suggestions for adapting content and features, for example, in relation to community resources, volume of text, universal accessibility (eg, for individuals with limitations in vision), and optimization of platform accessibility through mobile devices. Additional aspects of the innovation were flagged for adaptation during the final stages of preparing it for live implementation. These included terms of use, time zone configuration to reflect local time and date, safety and moderation protocols, the need help now feature, and the list of trigger words to flag posts indicative of potential risk. ConclusionsIn the context of the COVID-19 pandemic and public health guidelines for social distancing, there is an increasing interest and need to leverage the internet and mobile technologies for delivering youth mental health services. As countries look to one another for guidance on how to navigate changing social dynamics, knowledge on how to utilize and adapt existing innovations across contexts is now more important than ever. Using a systematic approach, this study illustrates the methods, processes, results, and lessons learned on adapting a digital health innovation to enhance its local acceptability. International Registered Report Identifier (IRRID)RR2-10.2196/resprot.8810

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., Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most common early-onset neurobehavioural disorders, with a worldwide prevalence of 5.9%-7.1% in the school-aged population. (1) It is a complex disorder involving [...]

'Perhaps the history of errors of mankind, all things considered, is more valuable and interesting than that of their discoveries. Truth is uniform and narrow.. .but error is endlessly diversified.'--Benjamin [...]

The information in this column is not intended as a definitive treatment strategy but as a suggested approach for clinicians treating patients with similar histories. Individual cases may vary and [...]

'One Toss of the Dice Will Never Abolish Chance' --Stephane Mallarme, 1898 Randomness and selection are fundamental processes rooted in the very basis of life, as postulated by the theory [...]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis – and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nine months before presentation, a 29-year-old patient had his university studies interrupted because of a 1-month psychiatric hospital admission for a first episode of psychosis. His auditory hallucinations and grandiose [...]