18q Deletion Syndrome-Associated Schizophrenia: A Case Report.

INTRODUCTION: 18q deletion syndrome is a rare genetic disorder characterized by various neurodevelopmental anomalies and medical issues. Although the occurrence of psychosis has been reported in a small number of cases, details regarding the nature of such symptoms and their response to treatment have not been described. CASE PRESENTATION: We describe a 31-year-old male with a history of speech delays, autistic features, a tethered spinal cord, bilateral vertical talus, subaortic stenosis and aortic regurgitation, recurrent otitis media, mild hearing loss, and hypospadias, who experienced a first episode of psychosis in his late 20s. His psychotic symptoms included auditory hallucinations, various delusions, and disorganization of thought. Although his presentation is atypical in certain ways (e.g., exhibiting highly fluctuant symptoms), he nonetheless meets criteria for schizophrenia. Given his overall clinical picture, chromosomal microarray analysis was completed, which revealed a 19.78 Mb deletion at 18q21.32 from nucleotide 58,226,713 to 78,015,180 (GRCh37). Despite exhibiting a somewhat idiosyncratic response to numerous antipsychotic medications, he eventually achieved partial remission of symptoms with improved insight on relatively low dose oral aripiprazole therapy. CONCLUSION: This is the first in-depth description of 18q deletion syndrome-associated schizophrenia. While our patient's atypical presentation and idiosyncratic response to treatment may be mediated by his comorbid diagnosis of autism, his unusual psychiatric phenotype may alternatively be directly related to his underlying genetic disorder. The description of additional cases in the future will hopefully help clarify matters further.

Preferences of Young Adults With Psychosis for Cannabis-Focused Harm Reduction Interventions: A Cross-Sectional Study: Préférences des jeunes adultes souffrant de psychose pour les interventions de réduction des méfaits axées sur le cannabis : une étude transversale.

OBJECTIVES: Cannabis use is common in people with early-phase psychosis (EP) and is associated with worse treatment outcomes. Few targeted interventions for cannabis use behaviour in this population exist, most focusing on abstinence, none focusing on harm reduction. Many people with EP will not seek treatment for their cannabis use with current therapeutic options. Understanding preferences for cannabis-focused harm reduction interventions may be key to improving outcomes. This study aimed to determine preferences of young adults with EP who use cannabis for cannabis-focused harm reduction interventions. METHODS: Eighty-nine young adults across Canada with EP interested in reducing cannabis-related harms were recruited. An online questionnaire combining conventional survey methodology and two unique discrete choice experiments (DCEs) was administered. One DCE focused on attributes of core harm reduction interventions (DCE 1) and the second on attributes of boosters (DCE 2). We analysed these using mixed ranked-ordered logistic regression models. Preference questions using conventional survey methodology were analysed using summary statistics. RESULTS: Preferred characteristics for cannabis-focused harm reduction interventions (DCE 1) were: shorter sessions (60 min vs. 10 min, odds ratio (OR): 0.72; P < 0.001); less frequent sessions (daily vs. monthly, OR: 0.68; P < 0.001); shorter interventions (3 months vs. 1 month, OR: 0.80; P < 0.01); technology-based interventions (vs. in-person, OR: 1.17; P < 0.05). Preferences for post-intervention boosters (DCE 2) included opting into boosters (vs. opting out, OR: 3.53; P < 0.001) and having shorter boosters (3 months vs. 1 month, OR: 0.79; P < 0.01). Nearly half of the participants preferred to reduce cannabis use as a principal intervention goal (vs. using in less harmful ways or avoiding risky situations). CONCLUSIONS: Further research is required to see if technology-based harm reduction interventions for cannabis featuring these preferences translate into greater engagement and improved outcomes in EP patients.

Whole-genome sequencing analysis of clozapine-induced myocarditis.

One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p < 0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.

Are There Therapeutic Benefits of Cannabinoid Products in Adult Mental Illness?

A position statement developed by the Canadian Psychiatric Association's (CPA) Research Committee and approved by the CPA's Board of Directors on May 13, 2020.

Canadian Schizophrenia Guidelines: Schizophrenia and Other Psychotic Disorders with Coexisting Substance Use Disorders.

OBJECTIVE: Persons with schizophrenia and other psychotic disorders frequently have coexisting substance use disorders that require modifications to treatment approaches for best outcomes. The objectives of this review were to identify evidence-based practices best practices that improve outcomes for individuals with schizophrenia and substance used disorders. METHOD: We reviewed guidelines that were published in the last 5 years and that included systematic reviews or meta-analyses. Most of our recommendations came from 2 publications from the National Institute for Health and Care Excellence (NICE): the 2011 guidance titled Coexisting Severe Mental Illness (Psychosis) and Substance Misuse: Assessment and Management in Healthcare Settings and the 2014 guidance titled Psychosis and Schizophrenia in Adults: Prevention and Management. We placed these recommendations into the Canadian context to create this guideline. RESULTS: Evidence supports the inclusion of individuals with coexisting substance use disorders in first-episode psychosis programs. The programs should integrate psychosis and substance use treatments, emphasizing ongoing monitoring of both substance use and patterns and symptoms. The best outcomes are achieved with combined use of antipsychotic medications and addiction-based psychosocial interventions. However, limited evidence is available to recommend using one antipsychotic medication over another or one psychosocial intervention over another for persons with schizophrenia and other psychotic disorders with coexisting substance use disorders. CONCLUSIONS: Treating persons who have schizophrenia and other psychotic disorders with coexisting substance use disorders can present clinical challenges, but modifications in practice can help engage and retain people in treatment, where significant improvements over time can be expected.

Cannabis use disorder and adverse cardiovascular outcomes: A population-based retrospective cohort analysis of adults from Alberta, Canada.

AIM: To measure the association between cannabis use disorder (CUD) and adverse cardiovascular disease (CVD) outcomes. DESIGN AND SETTING: We conducted a matched, population-based retrospective cohort study involving five linked administrative health databases from Alberta, Canada. PARTICIPANTS: We identified participants with CUD diagnosis codes and matched them to participants without CUD codes by gender, year of birth and time of presentation to the health system. We included 29 764 pairs (n = 59 528 individuals in total). MEASUREMENTS: CVD events were defined by at least one incident diagnostic code within the study period (1 January 2012-31 December 2019). Covariates included comorbidity, socio-economic status, prescription medication use and health service use. Using mortality-censored Poisson regression models, we computed survival analyses for time to incident CVD stratified by CUD status. In addition, we calculated crude and stratified risk ratios (RRs) across various covariates using the Mantel-Haenszel technique. FINDINGS: The overall prevalence of documented CUD was 0.8%. Approximately 2.4% and 1.5% of participants in the CUD and unexposed groups experienced an incident adverse CVD event (RR = 1.57; 95% confidence interval = 1.40-1.77). CUD was significantly associated with reduced time to incident CVD event. Individuals who appeared to have greater RRs for incident CVD were those without mental health comorbidity, who had not used health-care services in the previous 6 months, who were not on prescription medications and who did not have comorbid conditions. CONCLUSIONS: Canadian adults with cannabis use disorder appear to have an approximately 60% higher risk of experiencing incident adverse cardiovascular disease events than those without cannabis use disorder.

Systematic review protocol to determine the most effective pharmacological and non-pharmacological interventions for the management of acute methamphetamine toxicity.

INTRODUCTION: This study describes the protocol for a systematic review. The systematic review will address experiences of managing methamphetamine intoxication, specifically violence and agitation related to intoxication, in the emergency department (ED). METHODS AND ANALYSIS: This study uses the Grading of Recommendations Assessment, Development and Evaluation system to guide the methods in this section. The primary objective of the review is to identify experimental studies assessing the effectiveness of both pharmacological and non-pharmacological strategies to manage acute methamphetamine intoxication in patients presenting violently in the ED. Our secondary objectives will be to assess the impact of specific strategies on the time it takes to achieve de-escalation and/or sedation, the length of stay in the ED, frequency of admission, mortality and provider satisfaction with the intervention. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Conjoint Health Research Ethics Board REB21-1387. Results will be published in a peer-reviewed journal and presented at healthcare conferences in Canada. TRIAL REGISTRATION NUMBER: The protocol is registered through the International Prospective Register of Systematic Reviews (identification number: CRD42020157938) and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for systematic review protocols.

Navigating Evidence, Challenges, and Caution in the Treatment of Stimulant Use Disorders.

Amidst the opioid epidemic, harm reduction-oriented approaches have gained traction, including interventions that focus on prescribing pharmaceutical-grade psychoactive substances, such as opioids, instead of illicit versions, intending to mitigate fatal overdose risks arising from the variability in potency and additives found in illicit drugs. Stimulants have increasingly been found in the victims of opioid overdoses, further prompting some to argue for the prescription of stimulant medications for individuals with stimulant use disorders. Yet, the evidence supporting this practice remains insufficient. In this communication, we critically examine the existing evidence, challenges, and cautions surrounding the treatment of stimulant use disorder.

Assessing research competency development in Canadian psychiatry residency programs: A systematic review and future directions.

Objective: We aimed to conduct a systematic review to identify curricular and educational interventions to build research competency among Canadian psychiatry residents and fellows transitioning to the competency-by-design framework. Methods: The PRISMA guidelines were followed, searching five databases from their inception to February 2023 for relevant evaluation-type studies exploring research competency among psychiatry residents and fellows. We appraised thestudy's quality using the Joanna Briggs Institute's risk of bias tool for observational designs. Results: Overall, 36 original articles met our inclusion criteria. Surveys (n = 10) showed that participation in scholarly research, quality improvement, or educational projects relevant to psychiatry is needed in most residency programs. However, these vary significantly across programs; few need direct research experience for residency completion. The interventions spanned four categories: externally funded comprehensive research training programs (n = 5); resident research tracks (n = 11); workshops and seminars (n = 7); and specific modules (n = 3). Reported outcomes included overall program ratings, research output, and career trajectory. The quality of most studies was low because of the lack of controls or validated metrics for evaluating outcomes. Conclusions: While many studies have explored best practices in research curricula, the current literature does not inform competency-based models for Canadian psychiatry residency programs incorporating research training requirements. Further description is needed from Canadian psychiatric training bodies regarding appropriate curricula, milestones, and metrics for evaluating research competencies.

Evaluating preferences for online psychological interventions to decrease cannabis use in young adults with psychosis: An observational study.

Innovative technology-based solutions have the potential to improve access to clinically proven interventions for cannabis use disorder (CUD) in individuals with first episode psychosis (FEP). High patient engagement with app-based interventions is critical for achieving optimal outcomes. 104 individuals 18 to 35 years old with FEP and CUD from three Canadian provinces completed an electronic survey to evaluate preferences for online psychological intervention intensity, participation autonomy, feedback related to cannabis use, and technology platforms and app functionalities. The development of the questionnaire was informed by a qualitative study that included patients and clinicians. We used Best-Worst Scaling (BWS) and item ranking methodologies to measure preferences. Conditional logistic regression models for BWS data revealed high preferences for moderate intervention intensity (e.g., modules with a length of 15 min) and treatment autonomy that included preferences for using technology-based interventions and receiving feedback related to cannabis use once a week. Luce regression models for rank items revealed high preferences for smartphone-based apps, video intervention components, and having access to synchronous communications with clinicians and gamification elements. Results informed the development of iCanChange (iCC), a smartphone-based intervention for the treatment of CUD in individuals with FEP that is undergoing clinical testing.

Evaluation of a Cannabis Harm Reduction Intervention for People With First-Episode Psychosis: Protocol for a Pilot Multicentric Randomized Trial.

BACKGROUND: Cannabis use is highly prevalent in young people with first-episode psychosis (FEP). Most report cannabis use and are often diagnosed with a cannabis use disorder upon admission to specialized services for psychosis. Cannabis use in this population is associated with worse clinical and psychosocial outcomes, rendering it an important clinical target. Despite this, few cannabis-specific interventions have been developed for FEP and empirically evaluated through randomized controlled trials. Most evaluated interventions have targeted cannabis abstinence, with limited efficacy, but none have centered on harm reduction outcomes for people with FEP who use cannabis. Early intervention services (EIS), the standard of care for FEP, have not successfully addressed problematic cannabis use in people with FEP either. Clinical trials are needed to explore the potential of harm reduction strategies, although these should be preceded by robust pilot studies to establish optimal design and approaches. OBJECTIVE: Recognizing the need for harm reduction strategies for individuals with FEP who use cannabis and based on research on patients' preferences supporting harm reduction interventions, we developed a mobile app-based cannabis harm reduction intervention for this population. This intervention is called Cannabis Harm-reducing Application to Manage Practices Safely (CHAMPS). Here, we describe the protocol for a multicenter, 2-arm, parallel group, randomized pilot trial evaluating the acceptability of CHAMPS for people with FEP who use cannabis and the feasibility of conducting a full-scale trial in this population using CHAMPS. The impact on key clinical outcomes will also be explored. METHODS: This pilot trial aims to recruit 100 young people with FEP using cannabis from 6 Canadian EIS clinics. Participants will be randomized in a 1:1 ratio to CHAMPS+EIS or EIS-only. CHAMPS acceptability will be assessed using completion rates for the intervention arm. Trial feasibility will be assessed using a retention rate for randomized participants. Secondary outcomes will explore tendencies of change in the use of protective behavioral strategies and in motivation to change strategies. Exploratory outcomes include cannabis use-related problems, other substance use, the severity of dependence, psychotic symptoms, and health care service use. RESULTS: Recruitment began in December 2021. Data collection and analysis are expected to be completed in early 2024. Study results describing CHAMPS acceptability and trial feasibility will then be submitted for publication in a peer-reviewed journal. CONCLUSIONS: CHAMPS uniquely combines evidence-based approaches, patient perspectives, and mobile health technology to support harm reduction in people with FEP who use cannabis. Attaining adequate acceptability and feasibility through this trial may justify further exploration of harm reduction tools, particularly within the context of conducting a larger-scale randomized controlled trial. This pilot trial has the potential to advance knowledge for researchers and clinicians regarding a feasible and user-acceptable research design in the cannabis and early psychosis fields. TRIAL REGISTRATION: ClinicalTrials.gov NCT04968275, https://clinicaltrials.gov/ct2/show/NCT04968275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53094.

Neural correlates of pathological gamblers preference for immediate rewards during the iowa gambling task: an fMRI study.

The Iowa Gambling Task (IGT) involves exploratory learning via rewards and penalties, where most advantageous task performance requires subjects to forego potential large immediate rewards for small longer-term rewards to avoid larger punishments. Pathological gambling (PG) subjects perform worse on the IGT compared to controls, relating to their persistence at high risk decisions involving the continued choice of potential large immediate rewards despite experiencing larger punishments. We wished to determine if neural processing of risk and reward within striatal and frontal cortex is associated with this behaviour observed in PG. Functional magnetic resonance imaging (fMRI) was used to assess brain activity in response to a computerized version of the IGT. Thirteen male PG subjects with no active comorbidities were compared to 13 demographically matched control subjects. In agreement with previous behavioural studies, PG subjects performed worse on the IGT and made more high-risk choices compared to controls, particularly after experiencing wins and losses. During high-risk gambling decisions, fMRI demonstrated that PG subjects exhibited relatively increased frontal lobe and basal ganglia activation, particularly involving the orbitofrontal cortex (OFC), caudate and amygdala. Increased activation of regions encompassing the extended reward pathway in PG subjects during high risk choices suggests that the persistence of PG may be due to the increased salience of immediate and greater potential monetary rewards relative to lower monetary rewards or potential future losses. Whether this over activation of the reward pathway is associated with the development of PG warrants further investigation.

Neurobiology and Symptomatology of Post-Acute Alcohol Withdrawal: A Mixed-Studies Systematic Review.

OBJECTIVE: This study aims to review the neurobiology and symptomatology of post-acute alcohol withdrawal syndrome (PAWS). METHOD: We conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-guided systematic review of articles from two databases for English-language randomized and nonrandomized studies involving PAWS published between database inception and December 2020. RESULTS: Twenty-seven studies met inclusion criteria. PAWS involves predominantly negative affect, which develops in early abstinence and can persist for 4-6 months or longer. Symptoms include anxiety, dysphoria, anhedonia, sleep disturbance, cognitive impairment, cravings, and irritability. PAWS symptoms appear to be risk factors for recurrent alcohol consumption. They have been associated with reported neurobiological differences in evoked potentials; measures of orexins, cortisol, serotonin, and pancreatic polypeptides; and neuroadaptation changes in the nucleus accumbens and the prefrontal cortex. CONCLUSIONS: There is credible evidence to support the concept of PAWS based on this review's findings. There remains a need to develop and test specific criteria for PAWS. High-quality treatment studies involving agents addressing its neurobiological underpinnings are also recommended.