Centre for Addiction and Mental Health

Aim: This paper provides a detailed account of the process and outcomes involved in adapting a psychosocial intervention – the Optimal Health Program (OHP) – for young individuals who are at clinical high risk (CHR) for psychosis. This adaptation process included the active participation of youth with lived experience of psychosis spectrum disorder (CHR and first episode psychosis). Methods: A six-member advisory group consisting of youth with lived experience was established. The group convened weekly to review the OHP workbook in detail. This initiative was supported by a dedicated research assistant. Adherence to established guidelines for engaging with youth was maintained throughout. Following the completion of the adaptation, a review session was conducted to gather feedback. Results: The primary adaptations made to the intervention can be categorized as follows: 1) modification of language; 2) tailoring to the CHR population; 3) incorporation of personal stories; 4) emphasis on personalized recovery; 5) inclusion of ‘guiding and supportive activities’; 6) enhancement of graphic design. Suggestions for a digital application were not integrated due to their scope extending beyond the aims of the current project. An assessment of the engagement process revealed that the involvement of youth was meaningful and impactful. Conclusions: Through sustained and meaningful engagement with youth with lived experience, the present project adapted OHP for CHR individuals. The resulting intervention materials are anticipated to be closely aligned with the distinct needs and priorities of young CHR individuals. Subsequent endeavours in developing appropriate interventions that aim to improve outcomes for this population should involve engaging and collaborating with individuals with lived experience. We are currently in the process of evaluating the feasibility, acceptability, and preliminary efficacy of delivering OHP to individuals with CHR in a clinical trial.

Background In the present study, we extend previous psychometric evaluations of the DSM‐5 alcohol use disorder (AUD) criteria using Rasch analysis in a large clinical sample. Methods Adult patients with AUD (N = 1101) completed the DSM‐5 AUD symptom checklist as part of routine clinical assessment upon admission to an inpatient substance use disorder treatment program. We conducted Rasch analysis of responses to the 11 criteria, examining model fit and item severities. We also examined whether there was evidence of differential item functioning based on sex and age. Results Results supported the unidimensionality and local independence of the criteria, although some items were a suboptimal fit to the Rasch model. In particular, across all indicators, hazardous use exhibited misfit with model expectations. Additionally, the range of item severities did not span the full range of problem severity within this clinical sample, with many patients at the high end of the severity continuum and no items to differentiate them. There was evidence of differential item functioning by both sex and age, but effect size indices suggested that differences were unlikely to be clinically meaningful. Conclusions The present study supports the unidimensionality of the DSM‐5 AUD diagnosis, but the misfit of certain items to the Rasch model and the narrow range of item severities suggest that more granular distinctions in AUD may be limited in high‐severity samples. The results also suggest that the assumptions of interval‐level measurement may not hold in clinical populations.

The electroencephalographic alpha rhythm is one of the most robustly observed and widely studied empirical phenomena in all of neuroscience. However, despite its extensive implication in a wide range of cognitive processes and clinical pathologies, the mechanisms underlying alpha generation in neural circuits remain poorly understood. In this paper we offer a renewed foundation for research on this question, by undertaking a systematic comparison and synthesis of the most prominent theoretical models of alpha rhythmogenesis in the published literature. We focus on four models, each studied intensively by multiple authors over the past three decades: (i) Jansen-Rit, (ii) Moran-David-Friston, (iii) Robinson-Rennie-Wright, and (iv) Liley-Wright. Several common elements are identified, such as the use of second-order differential equations and sigmoidal potential-to-rate operators to represent population-level neural activity. Major differences are seen in other features such as wiring topologies and conduction delays. Through a series of mathematical analyses and numerical simulations, we nevertheless demonstrate that the selected models can be meaningfully compared, by associating parameters and circuit motifs of analogous biological significance. With this established, we conduct explorations of rate constant and synaptic connectivity parameter spaces, with the aim of identifying common patterns in key behaviours, such as the role of excitatory-inhibitory interactions in the generation of oscillations. Finally, using linear stability analysis we identify two qualitatively different alpha-generating dynamical regimes across the models: (i) noise-driven fluctuations and (ii) self-sustained limit-cycle oscillations, emerging due to an Andronov-Hopf bifurcation. The comprehensive survey and synthesis developed here can, we suggest, be used to help guide future theoretical and experimental work aimed at disambiguating these and other candidate theories of alpha rhythmogenesis.

Prior studies suggested that children’s appraisals of gender-nonconforming, compared with gender-conforming, peers are less positive, particularly for gender-nonconforming boys. To gauge appraisals, most prior studies used verbal reports, which provide explicit measures. In contrast, the current study explored facial emotional expressions, which can potentially be an objective and implicit measure to inform the emotional component of appraisals. We examined 4-, 5-, 8-, and 9-year-olds in Hong Kong (n = 309) and Canada (n = 296) (N = 605; 303 boys, 302 girls). Children’s faces were video-recorded while viewing four vignettes of hypothetical gender-conforming and gender-nonconforming boy and girl targets in random order. Targets were shown as having gendered preferences in the domains of toys, activities, clothing and hairstyle, and playmates. FaceReader software was used to perform automated coding of six basic facial emotional expressions: angry, disgusted, happy, sad, scared, and surprised. Children showed more scared emotion toward the hypothetical gender-nonconforming boy target when compared with the gender-conforming boy target. Also, this elevation in scared emotion was correlated with children verbally reporting that they perceived the gender-nonconforming boy as being less happy relative to the gender-conforming boy. These results suggest that, during a brief initial exposure to a target peer, gender nonconformity in boy peers was related to a relatively heightened fear response in early and middle childhood. Further, facial emotional expressions can be used to gain insights regarding the emotional component of children’s appraisals of varying peer gender presentations, and these emotional responses can be associated with certain other aspects of their appraisals.

Recent developments in mathematical modelling of EEG enable the tracking of otherwise-inaccessible neurophysiological parameters throughout sleep. Likewise, advancements in wearable electronics have enabled easy & affordable collection of sleep EEG at home. The convergence of these two advances, namely neurophysiological modelling for mobile sleep EEG, can boost preclinical and clinical assessments of sleep. However, this subject area has received limited attention in existing literature. To address this, we used an established model of the corticothalamic system to analyze EEG power spectra from 5 datasets, spanning from research-grade systems to at-home mobile EEG. In the present work, we compare the convergent and divergent features of the data and the estimated physiological model parameters. While data quality and characteristics differ considerably, key patterns consistent with previous theoretical and empirical work are observed. During the transition from lighter to deeper NREM, i) exponent of the aperiodic (1/f) spectral component is increased, ii) bottom-up thalamocortical drive is reduced, iii) corticocortical connection strengths are increased. This effect is observed in healthy subjects but is interestingly absent when taking SSRI antidepressants, suggesting possible effects of ascending neuromodulation on corticothalamic oscillations. We further show a month-long increase in REM% in one mobile EEG subject, associated with boosted highfrequency activity in spectra and higher thalamothalamic gains in the model, pointing to possible changes of thalamic inhibition in REM parasomnias. Our results provide a proof-of-principle for the utility and feasibility of this physiological modelling-based approach to analyzing mobile EEG data, providing a mechanistic measure of brain physiology during sleep.

Introduction: Social Determinants of Health (SDoH) include factors such as economic stability, education, social and community context, healthcare access, and the physical environment, which shape an individual's health and well-being. Given that the inclusion of SDoH factors is essential in improving the quality and equity of digital health, this study aims to examine how SDoH is incorporated within digital health policies internationally. Methods: An environmental scan of digital health policies was conducted, including relevant documents from multiple countries and global organizations. Key content related to SDoH was extracted from the documents, and a content analysis was conducted to identify seven different SDoH domains (i.e., target audience, SDoH inclusion, addressing health inequities, SDoH-related key performance indicators, data collection on SDoH, interoperability standards, and data privacy and security). Data were aggregated at the global and continental levels to integrate and synthesize information from different countries and regions. Results: A total of 28 digital health policies or strategies were identified across 16 international regions. The comparative analysis of health policies regarding SDoH reveals a pronounced disparity between the continental regions. Although the World Health Organization recognizes the significance of key performance indicators for monitoring SDoH and emphasizes the assessment of national digital health maturity, there's a noticeable lack of continent-specific policies reflecting these global initiatives at the continental level. Conclusion: While some regional digital health strategies recognize SDoH, integration varies, and standardization is lacking. Future research should focus on data collection frameworks and comprehensive insights for policymakers.

Background Many people who contract the SAR-CoV-2 virus present with multiple persistent and debilitating physical, cognitive and mental health symptoms that endure beyond the acute infection period. This new syndrome – generally referred to as long COVID – negatively affects patients’ emotional wellbeing and quality of life, and presents a major challenge for treatment providers. Considering the lack of evidence-based treatment and supports, this qualitative descriptive study explores the experiences of Canadian health and social service providers working with individuals with long COVID, as well as their suggestions for intervention development. Methods Twenty health and social service providers between the ages of 29 and 57 across Canada completed virtual individual interviews to discuss their care experiences and service recommendations for long COVID. Participants were from a range of service sectors, including primary care, rehabilitation, mental health, and community support. Interviews were recorded, transcribed, and analyzed using codebook thematic analysis. Results Four themes illustrated providers’ the experiences of (1) selecting personalized treatments based on patient presentation and similar conditions amidst uncertainty; and their recommendations for long COVID services, including (2) building an integrated and evidence-based model of care; (3) providing holistic support for patients and families through psychoeducation and daily living resources; and (4) caring for mental health in long COVID. Conclusions Canadian health and social service providers are adopting personalized treatment approaches to address the symptom persistence of long COVID in the face of a considerable knowledge gap. A comprehensive, integrated care pathway is needed to support patients’ physical and psychosocial wellbeing while increasing provider preparedness to treat this complex condition.

Purpose To contrast changes in suicide-related media reporting quality during parallel initiatives to engage national media in Canada and Israel. Methods We coded media articles in Canada’s and Israel’s highest circulating newspapers (major broadsheet and tabloid newspapers, respectively) for putatively harmful and putatively protective suicide-related content. A sample of 150 articles (30/year) from each country was randomly selected for three time points: 2012 (T1; prior to media engagement), 2016–2017 (T2; early media engagement), and 2018–2019 (T3; late media engagement). Chi-square tests and binary logistic regression investigated overall between-country differences in reporting quality over time. Results Following media engagement, adherence to guidelines improved over time in both countries for most variables. Over time, fewer Canadian and more Israeli articles covered celebrity suicide (OR = 4.97; 95%CI 1.68–16.69); more Canadian and fewer Israeli articles covered warning signs for suicide (OR = 0.30; 95%CI 0.12–0.78). Comparing articles over the entire timespan (T1-T3), a higher proportion of Israeli tabloid articles included putatively harmful content, such as mentioning suicide means (Israel: 65.3% vs. Canada 25.3%, χ²(1) = 48.4, p < 0.001), and a higher proportion of Canadian broadsheet articles included putatively protective content, such as providing information on intervention (Israel: 2.0% vs. Canada 27.3%, χ²(1) = 38.5, p < 0.001). Conclusion Media engagement appeared to confer benefits in both countries and publication formats. A higher proportion of Canadian articles adhered to several specific recommendations. Our findings must be interpreted in the context of differences in format between major Canadian and Israeli newspapers (broadsheet vs. tabloid) and the much higher total volume of suicide-related articles in Canada.

Psychiatric conditions are often linked to dysfunction of the Hypothalamic–Pituitary–Adrenal (HPA) axis. The Endocannabinoid System (ECS) plays a significant role in stress and anxiety and interacts with the HPA axis. The ECS metabolizing enzyme, Fatty Acid Amide Hydrolase (FAAH), may be integral for HPA axis response to stress by reducing levels of the endocannabinoid anandamide (AEA). However, there is conflicting evidence regarding the effects of FAAH inhibition on stress-related hormone changes, and no comprehensive evaluation of this literature exists. This review aims to synthesize the literature on the impact of pharmacological FAAH inhibition on corticosterone levels in rodents. A systematic search of PubMed/MEDLINE, APA PsychInfo, and Embase up to July 2024 was conducted. Articles reporting the effects of FAAH inhibition on corticosterone levels in rodents were included. Risk of Bias was assessed using SYRCLE’s Risk of Bias tool. This review included 21 articles. FAAH inhibition showed limited effects depending on type of FAAH inhibitor, stress exposure, and rodent age. Selective FAAH inhibition did not significantly affect corticosterone levels in the absence of stress and showed minimal effects following acute stress. After chronic stress, these compounds showed more pronounced effects, reducing corticosterone in 40% of studies. Limited studies employing flavonoid-based and dual FAAH/TRPV1 inhibitors suggested blunted corticosterone after acute, but not chronic stress. This review found that FAAH inhibition has inconsistent effects on corticosterone regulation, highlighting the complex and context-dependent role of FAAH inhibition in modulating stress hormone responses, warranting further investigation to clarify its therapeutic potential in stress-related disorders.

Schizophrenia spectrum disorders (SSD) are a complex group of illnesses, and their pathophysiology remains unclear. Recent developments in neuroimaging techniques provided useful quantitative measures, such as quantitative T1 mapping (qT1) that is susceptible to tissue-level, microscopic changes. However, it is important to identify the most sensitive, accurate, and reliable imaging protocol, given the complex nature of SSD. We compared structural brain changes in a pilot sample of 15 SSD patients and 7 healthy controls, cross-sectionally, and using two different qT1 mapping protocols. Our findings showed a global elevation in qT1 values in SSD patients, that was statistically significant in the lateral ventricles, thalamus, caudate, and hippocampus (p < 0.01). Moreover, the two acquisition protocols were differently modulated by demographic factors, such as age, sex, and education, which further illustrates the importance of protocol selection. In conclusion, this investigation revealed microstructural tissue changes in subcortical regions in SSD patients, providing further insights into the pathophysiology of the illness.

With the many negative health consequences of cigarette smoking, quitting is known to improve health in multiple domains. Using positron emission tomography/computed tomography (PET/CT) scanning, our group previously demonstrated that smokers have lower levels than nonsmokers of translocator protein binding both acutely and following overnight abstinence. Here, we sought to determine the effects of longer smoking abstinence on this marker of gliosis for microglia and astroglia, as well as explore associations between the marker and smoking‐related symptoms. This observational study was performed in an academic VA medical centre. Fifty‐nine generally healthy Veterans who were either nonsmokers (n = 15) or smokers (n = 44) participated in the study. Participants completed an intake visit to evaluate for inclusion/exclusion criteria, [¹⁸F]FEPPA PET/CT scanning and a structural magnetic resonance imaging scan. Smokers were alternately assigned either to smoke to satiety (n = 24) before scanning or undergo three nights of continuous abstinence prior to scanning using contingency management (n = 20 completed this protocol and scanning). The smoker satiety group had a significantly lower mean whole brain (WB) standardized uptake value (SUV) for [¹⁸F]FEPPA binding than both the nonsmoking (−15.3%) and abstinent smoker (−12.3%) groups. The nonsmoking control and abstinent smoker groups had mean WB SUVs that were not significantly different from one another (3.0% group difference). In an exploratory analysis, a significant inverse relationship was found between WB SUVs and mood ratings for smokers, indicating that higher levels of TSPO binding were associated with worse mood. The central findings here support previous studies demonstrating lower levels of the marker for gliosis in satiated smokers and imply normalization with elimination of cigarette smoke constituents from the body, although other explanations for study results (e.g., alterations in radioligand delivery or clearance of radioligand by cigarette smoke constituents) are possible. These findings may represent a previously unknown health benefit of quitting smoking.

The human brain exhibits a modular and hierarchical structure, spanning low-order sensorimotor to high-order cognitive/affective systems. What is the mechanistic significance of this organization for brain dynamics and information processing properties? We investigated this question using rare simultaneous multimodal electrophysiology (stereotactic and scalp electroencephalography - EEG) recordings in 36 patients with drug-resistant focal epilepsy during presurgical intracerebral electrical stimulation (iES) (323 stimulation sessions). Our analyses revealed an anatomical gradient of excitability across the cortex, with stronger iES-evoked EEG responses in high-order compared to low-order regions. Mathematical modeling further showed that this variation in excitability levels results from a differential dependence on recurrent feedback from non-stimulated regions across the anatomical hierarchy, and could be extinguished by suppressing those connections in-silico. High-order brain regions/networks thus show an activity pattern characterized by more inter-network functional integration than low-order ones, which manifests as a spatial gradient of excitability that is emergent from, and causally dependent on, the underlying hierarchical network structure. These findings offer new insights into how hierarchical brain organization influences cognitive functions and could inform strategies for targeted neuromodulation therapies.

Research Summary On January 31, 2023, British Columbia (BC) launched a 3‐year pilot initiative decriminalizing the possession of up to 2.5 g of select illegal drugs. The policy aims to reduce stigma, address racial disparities in drug law enforcement, and improve police relations with people who use drugs (PWUD). As part of a national evaluation, we conducted qualitative interviews with 100 PWUD who reported using drugs at least three times a week across BC between October 2023 and February 2024. Participants, diverse in sociodemographics, drug use patterns, and police interaction histories, largely reported an adversarial relationship with police, marked by historical mistreatment and the targeting of individuals based on aspects of their social identity, such as ethnicity, housing status, and other visible markers. Despite police generally adhering to the policy, some participants reported unlawful drug seizures, reinforcing mistrust. Although some noted reduced fear of police, most felt their negative perceptions persisted post‐decriminalization, highlighting a need for further police education and training to address stigma and inconsistent enforcement. Policy Implications Our findings underscore the need for improved police education and training through better standardization, with an emphasis on promoting consistency and increased transparency, particularly in the use of discretion. Training should also address the impact of systemic racism and discriminatory policing practices to foster equitable interactions with PWUD. Further consideration of alternative nonpunitive legal approaches, alongside expanded harm reduction services, treatment options, social supports (such as housing), and community‐based initiatives, could be highly beneficial. Continued monitoring and evaluation of the policy's impact on PWUD is essential.

Background Vaping is increasing in popularity. Vape products are offered in a wide variety and promise to reduce harms associated with cigarette smoking, among other claims. The motivations for vaping in patients with substance use disorder are largely unknown. Aims To describe perceptions and motivations regarding vaping among patients with opioid use disorder (OUD) who vape. Method A convergent mixed-methods study design was used, and individual, semi-structured interviews were conducted with 41 individuals with OUD who were receiving medication for OUD and also vaped. An inductive data-driven approach was employed to characterise perspectives on vaping. Results The mean ages at which participants had been introduced to vaping and initiated regular vaping were 33.95 years (s.d. 12.70) and 34.85 years (s.d. 12.38), respectively. Daily vaping (85%) of nicotine, flavoured nicotine or cannabis was common, with 27% reporting vaping both nicotine and cannabis. Qualitative analysis identified 14 themes describing motivations for vaping, including viewing vaping as a smoking cessation tool, convenience and popularity among youth. Conclusions Mixed-methods findings indicated that patients with OUD who vape perceived vaping to be healthier, cleaner and more convenient than cigarette and cannabis smoking, without appreciating the health risks. The perspectives reflected the importance of health education, guidelines and screening tools for vaping and could provide direction for healthcare providers and future vaping cessation programmes.

Anticipating clinical transitions in bipolar disorder (BD) is essential for the development of clinically actionable predictions. Our aim was to determine what is the earliest indicator of the onset of depressive symptoms in BD. We hypothesized that changes in activity would be the earliest indicator of future depressive symptoms. The study was a prospective, observational, contactless study. Participants were 127 outpatients with a primary diagnosis of BD, followed up for 12.6 (5.7) [(mean (SD)] months. They wore a smart ring continuously, which monitored their daily activity and sleep parameters. Participants were also asked to complete weekly self-ratings using the Patient Health Questionnaire (PHQ-9) and Altman Self-Rating Mania Scale (ASRS) scales. Primary outcome measures were depressive symptom onset detection metrics (i.e., accuracy, sensitivity, and specificity); and detection delay (in days), compared between self-rating scales and wearable data. Depressive symptoms were labeled as two or more consecutive weeks of total PHQ-9 > 10, and data-driven symptom onsets were detected using time-frequency spectral derivative spike detection (TF-SD²). Our results showed that day-to-day variability in the number of steps anticipated the onset of depressive symptoms 7.0 (9.0) (median (IQR)) days before they occurred, significantly earlier than the early prediction window provided by deep sleep duration (median (IQR), 4.0 (5.0) days; p <.05). Taken together, our results demonstrate that changes in activity were the earliest indicator of depressive symptoms in participants with BD. Transition to dynamic representations of behavioral phenomena in psychiatry may facilitate episode forecasting and individualized preventive interventions.

Background Genetics is an important contributor to autism spectrum disorder (ASD). Clinical guidelines endorse genetic testing in the medical workup of ASD, particularly tests that use whole genome sequencing (WGS) technology. While the clinical utility of genetic testing in ASD is demonstrated, the breadth of impact of results can depend on the variant and/or gene being reported. Methods We reviewed research results returned to families enrolled in our ASD WGS study between 2012 and 2023. For significant results, we grouped the outcome of each genetic finding into three outcome categories: (1) genetic diagnosis, (2) counselling benefits and (3) support to family. Results Out of 202 families who received genome sequencing results, 100 had at least one clinically relevant finding related to ASD. With detailed examples, we show that all significant results led to a genetic diagnosis and counselling benefits. Conclusion Our findings show the relevance of genome sequencing in ASD and provide illustrative examples of how the information can be used.