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.

Site qualification and clinical interpretation standards for 99mTc-SPECT perfusion imaging in a multi-center study of MITNEC (Medical Imaging Trials Network of Canada).

BACKGROUND: Qualification and interpretation standards are essential for establishing 99mTc-SPECT MPI accuracy vs. alternative modalities. METHODS: Rest-stress 99mTc-SPECT phantom scans were acquired on 35 cameras. LV defects were quantified with summed stress (SSS) and difference scores (SDS) at 2 core labs. SDS ≥ 2 in the right coronary artery (RCA) was the qualifying standard. Twenty rest (R)-stress (S) patient images were acquired on qualified cameras and interpreted by core labs. Global scoring differences > 3 between labs or discordant clinical interpretations underwent review. Scoring, interpretation, image quality, and diagnostic parameter agreement were assessed. RESULTS: Phantom scans: visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good: ICC-r = 0.57, 0.84. Patient scans: 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement: ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation: ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed: ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90. CONCLUSION: Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine 99mTc-SPECT MPI accuracy.

Aggressive behaviors in first-episode psychosis: Distinction between the premorbid phase and the onset of psychosis.

BACKGROUND: There is a well-established, although complex, association between aggression and psychosis, particularly in the early stages of illness. Some persons display aggressive behaviors even prior to psychosis onset. However, factors associated with aggressive behaviors prior to and at first-episode psychosis (FEP) onset remain underdocumented. AIMS: The objective is two-fold: 1) to describe the prevalence of verbal and physical aggression occurring during the premorbid phase and at FEP onset; 2) distinguish the factors associated with aggressive behaviors during these two periods. METHOD: Data on aggressive behaviors and factors potentially associated therewith were collected through research interviews and chart reviews among 567 persons with FEP admitted to two early intervention services in Montreal, Canada. Logistic regression analyses were conducted to identify factors associated with aggressive behaviors in both periods. RESULTS: In the premorbid phase, 46.1 % (n = 257/558) of patients presented aggression (verbal: 35.9 %; towards objects: 24.2 %; against others: 27.9 %). At FEP, 18.1 % (n = 101/558) presented aggressive behaviors (verbal: 12.9 %; towards objects: 6.1 %; against others: 8.8 %). In the premorbid phase, lower education, prior justice involvement, cluster B personality traits/disorder and poorer functioning were associated with aggressive behaviors, while, at FEP, only prior homelessness was associated with aggression. CONCLUSIONS: Aggressive behaviors are frequent in patients with FEP, prior onset and at FEP. Premorbid aggressive behaviors seem to be associated with premorbid difficulties. Early detection of youth with psychosis and those at high risk of psychosis, particularly homeless youth, is necessary to provide access to early specialized interventions and possibly prevent aggressive behaviors and their consequences.

Joint-trajectories of clinical severity, social functioning and cannabis use in first-episode psychosis: A 5-year longitudinal study in 2 urban early intervention services.

Cannabis use is associated with increased psychosis incidence alongside worse outcomes. The role of cannabis may be complex, vary across patients and over time. Yet, few have examined the longer-term trajectories of cannabis use, symptoms and functioning and their inter-relationships. We conducted a 5-year longitudinal study to estimate joint-trajectories of clinical severity, social functioning, and cannabis use via group-based multi-trajectory modelling on a sample of 395 incident FEP cases. Associations of trajectories with socio-demographic and clinical factors were tested using multinomial regression. The best-fitting model identified 5 joint-trajectories. A first group (N = 93,23.7 %) presented only marginal improvement despite not using cannabis, while a second with no cannabis use and a third group with low-decreasing use showed clinical amelioration. Among those with baseline harmful cannabis use, a fourth group progressively discontinued use and improved clinically (N = 78,19.9 %). A fifth group with continued use did not significantly improve over follow-up (N = 74,18.8 %), and also had the highest odds of homelessness (OR = 22.5,95 %CI = 6.25-81.1) and childhood adversities (OR = 2.25,95 %CI = 1.71-2.97). There is substantial heterogeneity in the joint-trajectories of cannabis use and FEP outcomes. Our findings support the need for intervention aimed at cannabis reduction among heavy users. Multi-disciplinary, trauma-informed interventions may benefit those with persistent cannabis use, given its associations with childhood and social adversity.

A Mobile Health App (ChillTime) Promoting Emotion Regulation in Dual Disorders: Acceptability and Feasibility Pilot Study.

BACKGROUND: A growing number of studies highlight the importance of emotion regulation in the treatment and recovery of individuals with psychosis and concomitant disorders such as substance use disorder (SUD), for whom access to integrated dual-disorder treatments is particularly difficult. In this context, dedicated smartphone apps may be useful tools to provide immediate support to individuals in need. However, few studies to date have focused on the development and assessment of apps aimed at promoting emotional regulation for people with psychosis. OBJECTIVE: The aim of this study was to evaluate the feasibility, acceptability, and potential clinical impact of a dedicated app (ChillTime) for individuals with psychotic disorders and concurrent SUD. The app design process followed recommendations for reducing cognitive effort on a mobile app. A total of 20 coping strategies regrouped in four categories (behavioral, emotional, cognitive, spiritual) were included in the app. METHODS: This open pilot study followed a pre-post design. After the initial assessment, researchers asked participants to use the app as part of their treatment over a 30-day period. Feasibility was determined by the frequency of use of the app and measured using the number of completed strategies. Acceptability was determined by measuring ease of use, ease of learning, satisfaction, and perceived utility at the end of the 30-day study period based on responses to satisfaction questionnaires. Clinical scales measuring emotion regulation, substance use (ie, type of substance, amount taken, and frequency of use), and various psychiatric symptoms were administered at the beginning and end of the 30-day period. RESULTS: A total of 13 participants were recruited from two first-episode psychosis clinics in Montreal, Quebec, Canada. All participants were symptomatically stable, were between 18 and 35 years of age (mostly men; 70% of the sample), and had a schizophrenia spectrum disorder with a comorbid substance use diagnosis. A total of 11 participants completed the study (attrition<20%). Approximately half of the participants used the tool at least 33% of the days (11-21 days). Cognitive and emotion-focused techniques were rated the highest in terms of usefulness and were the most frequently used. The majority of participants gave positive answers about the ease of use and the ease of learning the tool. A nonsignificant association of ChillTime use with negative symptoms and drug use was observed. No other statistically significant changes were observed. CONCLUSIONS: The ChillTime app showed good feasibility (approximately half of the participants used the tool at least 33% of the days) and acceptability among people with schizophrenia spectrum disorder and SUD. Trends suggesting a potential impact on certain clinical outcomes will need to be replicated in larger-sample studies before any conclusion can be drawn.

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.

Reducing Cannabis Use in Young Adults With Psychosis Using iCanChange, a Mobile Health App: Protocol for a Pilot Randomized Controlled Trial (ReCAP-iCC).

BACKGROUND: Cannabis use is the most prevalent among adolescents and young adults; frequent consumption is associated with cannabis use disorder (CUD) and psychosis, with a high prevalence (up to 50%) of CUD in individuals with first-episode psychosis (FEP). Early Intervention Services (EIS) for psychosis include face-to-face psychosocial interventions for CUD, because reducing or discontinuing cannabis use improves clinical and health care service use outcomes. However, multiple barriers (eg, staff availability and limited access to treatment) can hinder the implementation of these interventions. Mobile health (mHealth) interventions may help circumvent some of these barriers; however, to date, no study has evaluated the effects of mHealth psychological interventions for CUD in individuals with FEP. OBJECTIVE: This study describes the protocol for a pilot randomized controlled trial using a novel mHealth psychological intervention (iCanChange [iCC]) to address CUD in young adults with FEP. iCC was developed based on clinical evidence showing that in individuals without psychosis, integrating the principles of cognitive behavioral therapy, motivational interviewing, and behavioral self-management approaches are effective in improving cannabis use-related outcomes. METHODS: Consenting individuals (n=100) meeting the inclusion criteria (eg, aged 18-35 years with FEP and CUD) will be randomly allocated in a 1:1 ratio to the intervention (iCC+modified EIS) or control (EIS) group. The iCC is fully automatized and contains 21 modules that are completed over a 12-week period and 3 booster modules available during the 3-month follow-up period. Validated self-report measures will be taken via in-person assessments at baseline and at 6, 12 (end point), and 24 weeks (end of trial); iCC use data will be collected directly from the mobile app. Primary outcomes are intervention completion and trial retention rates, and secondary outcomes are cannabis use quantity, participant satisfaction, app use, and trial recruiting parameters. Exploratory outcomes include severity of psychotic symptoms and CUD severity. For primary outcomes, we will use the chi-square test using data collected at week 12. We will consider participation in iCC acceptable if ≥50% of the participants complete at least 11 out of 21 intervention modules and the trial feasible if attrition does not reach 50%. We will use analysis of covariance and mixed-effects models for secondary outcomes and generalized estimating equation multivariable analyses for exploratory outcomes. RESULTS: Recruitment began in July 2022, and data collection is anticipated to be completed in July 2024. The main results are expected to be submitted for publication in 2024. We will engage patient partners and other stakeholders in creating a multifaceted knowledge translation plan to reach a diverse audience. CONCLUSIONS: If feasible, this study will provide essential data for a larger-scale efficacy trial of iCC on cannabis use outcomes in individuals with FEP and CUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05310981; https://www.clinicaltrials.gov/ct2/show/NCT05310981. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40817.

[Early Detection and Intervention for Psychosis: Why and How?] / Détection et intervention précoce pour la psychose : pourquoi et comment ?

Objectives This article aims to synthesize the critical stages in the development of early detection and intervention services (EIS) for psychosis over the past 30 years, and to review key literature on the essential components and effectiveness of these programs. Method We conducted a narrative review of the literature on the international development of EIS leading to its endorsement as a service delivery model for young people with first-episode psychosis (FEP). We also reviewed various international and Canadian guidelines to identify consensus about the essential components of EIS for psychosis and their effectiveness. Challenges to the implementation of these different essential components are presented, along with practical solutions to addressing them. A particular emphasis is placed on implementing EIS in the Quebec context. Results Based on a model developed in the early 1990s, EIS for psychosis have now been disseminated worldwide and are deployed on a large scale in some regions, such as the United Kingdom and Quebec. The model's gradual expansion has been facilitated by efforts to identify its main objectives and the components essential to achieve them, and by several studies demonstrating its effectiveness. Along with an important philosophical shift to optimism and hope, EIS have typically focused on the twin aims of reducing treatment delay (or the duration of untreated psychosis) and enhancing engagement in specialized, phase-specific, developmentally appropriate treatment. A meta-analysis (published in 2018) demonstrated the superiority of EIS for psychosis compared to standard treatment on several outcomes including hospitalizations, relapse of symptoms, treatment discontinuation, and vocational and social functioning. Based on these studies and expert consensus, many jurisdictions around the world have developed guidelines to ensure compliance with essential components that are associated with the effectiveness of EIS, while accounting for their contextual realities. The components that have been prioritized include outreach to enable early identification and referral; rapid access to care and youth-friendly services; a range of biopsychosocial interventions (pharmacotherapy, cognitive behavioral therapy, psychoeducation, family interventions, integrated substance use interventions, employment and educational support); a shared-decision making approach; and the intensive case management approach adapted to FEP, which are all delivered by an interdisciplinary team. There is also increasing acknowledgement of the value of continuous evaluation that informs treatment decision-making and quality improvement. Conclusion EIS for psychosis have developed gradually and research has demonstrated its effectiveness. Disseminating the model in ways that ensure fidelity to its core values and the implementation of its essential components is needed to ensure effectiveness; and instill hope for recovery and improve the quality of lives of young people with psychosis and their families.

Group therapy via videoconferencing for individuals with early psychosis: A pilot study.

AIM: The COVID-19 pandemic has introduced many mental health professionals to therapy via videoconferencing. Mostly individual teletherapy has been offered and studied, although group therapy is often offered in clinics. In fact, little is known regarding group therapy's acceptability, feasibility, and potential impact when offered via videoconferencing. METHODS: This pilot study offered group cognitive-behavioural therapy for psychosis via videoconferencing to 14 individuals with early psychosis either living in remote areas or confined during the pandemic. RESULTS: The rate of consenting to the study (79%) and actual participation rates were acceptable (18.5 sessions out of 24). Although some technological obstacles were encountered, solutions offered allowed the videoconferencing group to be considered feasible for most participants and therapists. Prepost results on symptoms and self-esteem were comparable to those of other studies using the same group treatment but in-person. Alliance scores seemed similar as well. CONCLUSIONS: More studies are warranted on the efficacy of group therapy via videoconferencing. This pilot study does offer promising results, suggesting that a wider range of people with early psychosis can be reached and benefit from the advantages of receiving an evidence-based group intervention.

Abnormal visual representations associated with confusion of perceived facial expression in schizophrenia with social anxiety disorder.

Deficits in social functioning are especially severe amongst schizophrenia individuals with the prevalent comorbidity of social anxiety disorder (SZ&SAD). Yet, the mechanisms underlying the recognition of facial expression of emotions-a hallmark of social cognition-are practically unexplored in SZ&SAD. Here, we aim to reveal the visual representations SZ&SAD (n = 16) and controls (n = 14) rely on for facial expression recognition. We ran a total of 30,000 trials of a facial expression categorization task with Bubbles, a data-driven technique. Results showed that SZ&SAD's ability to categorize facial expression was impared compared to controls. More severe negative symptoms (flat affect, apathy, reduced social drive) was associated with more impaired emotion recognition ability, and with more biases in attributing neutral affect to faces. Higher social anxiety symptoms, on the other hand, was found to enhance the reaction speed to neutral and angry faces. Most importantly, Bubbles showed that these abnormalities could be explained by inefficient visual representations of emotions: compared to controls, SZ&SAD subjects relied less on fine facial cues (high spatial frequencies) and more on coarse facial cues (low spatial frequencies). SZ&SAD participants also never relied on the eye regions (only on the mouth) to categorize facial expressions. We discuss how possible interactions between early (low sensitivity to coarse information) and late stages of the visual system (overreliance on these coarse features) might disrupt SZ&SAD's recognition of facial expressions. Our findings offer perceptual mechanisms through which comorbid SZ&SAD impairs crucial aspects of social cognition, as well as functional psychopathology.

The hallmarks of castration-resistant prostate cancers.

Prostate cancer has become a real public health issue in industrialized countries, mainly due to patients' relapse by castration-refractory disease after androgen ablation. Castration-resistant prostate cancer is an incurable and highly aggressive terminal stage of prostate cancer, seriously jeopardizing the patient's quality of life and lifespan. The management of castration-resistant prostate cancer is complex and has opened new fields of research during the last decade leading to an improved understanding of the biology of the disease and the development of new therapies. Most advanced tumors resistant to therapy still maintain the androgen receptor-pathway, which plays a central role for survival and growth of most castration-resistant prostate cancers. Many mechanisms induce the emergence of the castration resistant phenotype through this pathway. However some non-related AR pathways like neuroendocrine cells or overexpression of anti-apoptotic proteins like Hsp27 are described to be involved in CRPC progression. More recently, loss of expression of tumor suppressor gene, post-transcriptional modification using miRNA, epigenetic alterations, alternatif splicing and gene fusion became also hallmarks of castration-resistant prostate cancer. This review presents an up-to-date overview of the androgen receptor-related mechanisms as well as the latest evidence of the non-AR-related mechanisms underlying castration-resistant prostate cancer progression.

Hyperinsulinemia is closely related to low urinary clearance of D-chiro-inositol in men with a wide range of insulin sensitivity.

We have previously shown that women with polycystic ovary syndrome (PCOS) have increased urinary clearance of D-chiro-inositol (uCl(DCI)), which was positively associated with hyperinsulinemia. The objective of this study was thus to determine if such relationship also exists in men with a large range of insulin sensitivity and levels. A cross-sectional study was performed on 11 brothers of women with PCOS and 21 control men. In this study, brothers served as a model of insulin resistance. We assessed uCl(DCI), urinary clearance of myo-inositol, and insulin levels with a standard 75-g oral glucose tolerance test, a 2-hour euglycemic-hyperinsulinemic clamp, and a 24-hour urine collection. Our results showed in all men together that low uCl(DCI) was strongly associated (P < .001) with hyperinsulinemia, for which uCl(DCI) was a significant predictor independent of other classic factors. Brothers were heavier than controls (P = .02), with increased glucose-stimulated glucose (P < .001) and insulin levels (P < .001) and reduced insulin sensitivity (P = .001). In this group, plasma DCI was increased by 3-fold (P = .02), with a 3-fold decrease in the uCl(DCI) to urinary clearance of myo-inositol ratio, which was almost significant (P = .07). Low uCl(DCI) is strongly associated with hyperinsulinemia in all men, and brothers of PCOS women who are more insulin resistant display increased plasma DCI and borderline decreased uCl(DCI). Thus, compensatory hyperinsulinemia might suppress renal clearance of DCI to increase plasma DCI levels and partially compensate for insulin resistance by improving DCI availability in men. The apparent discrepancy with PCOS women might be explained by higher insulin levels in men as compared with women and requires confirmation.