Psychotic-like experiences and associated factors in resident physicians: A Canadian cross-sectional study.

AIM: Medical residency training is associated with a range of sociodemographic, lifestyle and mental health factors that may confer higher risk for psychotic-like experiences (PLEs) in residents, yet little research has examined this question. Thus, we aimed to document the prevalence and associated factors of PLEs among resident physicians. METHODS: Physicians enrolled in residency programmes in the Province of Québec, Canada (four universities) were recruited in Fall 2022 via their programme coordinators and social media. They completed an online questionnaire assessing PLEs in the past 3 months (the 15-item Community Assessment of Psychic Experiences), as well as sociodemographic characteristics, lifestyle and mental health. Analyses included survey weights and gamma regressions. RESULTS: The sample included 502 residents (mean age, 27.6 years; 65.9% women). Only 1.3% (95% CI: 0.5%, 4.0%) of residents met the screening cut-off for psychotic disorder. Factors associated with higher scores for PLEs included racialised minority status (relative difference: +7.5%; 95% CI: +2.2%, +13.2%) and English versus French as preferred language (relative difference: +7.9% 95% CI: +3.1%, +12.9%), as well as each additional point on scales of depression (relative difference: +0.8%; 95% CI: +0.3%, +1.3%) and anxiety (relative difference: +1.3%; 95% CI: +0.8%, +1.7%). In secondary analyses, racialised minority status was associated with persecutory items, but not with other PLEs. Gender, residency programmes and lifestyle variables were not associated with PLEs. CONCLUSIONS: This study found low reports of PLEs in a sample of resident physicians. Associations of PLEs with minoritised status may reflect experiences of discrimination.

Hair steroid before and after COVID-19 in preschoolers: the moderation of family characteristics.

BACKGROUND: Frequent or prolonged exposure to stressors may jeopardize young children's health. The onset of the COVID-19 pandemic, coupled with disruptions in daily routines and social isolation resulting from public health preventive measures, have raised concerns about its potential impact on children' experienced stress, particularly for young children and vulnerable families. However, whether the pandemic was accompanied by changes in physiological stress remains unknown as perceived stress is not a good proxy of physiological stress. This study examined if preschoolers showed increasing hair steroid concentrations following the onset of the COVID-19 pandemic and whether family characteristics may have exacerbated or buffered these changes. METHODS: 136 preschoolers (2-4 years) provided hair for steroid measurement (cortisol, dehydroepiandrosterone (DHEA), cortisone, cortisol-to-DHEA ratio, cortisol-to-cortisone ratio) in October-November 2019 (T0) and in July-August 2020 (T1). A 2-centimeter hair segment was analyzed, reflecting steroid production over the two months leading up to collection. Family income, conflict resolution and lack of cohesion, as well as parents' COVID-19 stress were reported by parents. Linear mixed models for repeated measures and Bayes factors were used. RESULTS: No significant changes were noted from before to after the onset of the COVID-19 pandemic for most hair steroids. However, a moderating role of family conflict resolution was noted. Children living with parents with a better ability to resolve conflicts had lower levels of DHEA compared to those who had more difficulty managing conflicts. Additionally, lower levels of family cohesion and income were linked to some steroids, especially DHEA, suggesting that these factors may relate to children's physiological stress. Finally, boys had higher DHEA levels than girls. CONCLUSION: Our findings suggest that stress biomarkers were comparable from before to during the COVID-19 pandemic. This observation holds true despite the pandemic being perceived by many as a novel, unpredictable, and potentially threatening event. Findings further suggest that family characteristics are associated with hair steroid, especially DHEA, which deserves further investigation.

Longitudinal study of childhood sleep trajectories and adolescent mental health problems.

Study Objective: To investigate whether childhood sleep trajectories are associated with mental health symptoms such as social phobia, generalized anxiety, depression, attention deficit hyperactivity disorder (ADHD), conduct problems, and opposition at age 15. Methods: A total of 2120 children took part in the Quebec Longitudinal Study of Child Development. Childhood sleep trajectories were computed from maternal reports at 2.5, 3.5, 4, 6, 8, 10, and/or 12 years. At age 15, 1446 adolescents filled out mental health and sleep questions. A path analysis model was assessed in the full sample. Results: Four childhood nocturnal sleep duration trajectories were identified: (1) a short pattern (7.5%), (2) a short-increasing pattern (5.8%), (3) a 10 hours pattern (50.7%), and (4) an 11 hours pattern (36.0%). Three childhood sleep latency trajectories were found: (1) a short pattern (31.7%), (2) an intermediate pattern (59.9%), and (3) a long pattern (8.4%). Finally, two childhood wakefulness after sleep-onset trajectories were found: (1) a normative pattern (73.0%) and (2) a long pattern (27.0%). The path analysis model indicated that children following a long childhood sleep latency trajectory were more likely to experience symptoms of depression (ß = 0.06, 95% CI: 0.01 to 0.12), ADHD (ß = 0.07, 95% CI: 0.02 to 0.13), conduct problems (ß = 0.05, 95% CI: 0.00 to 0.10) and opposition (ß = 0.08, 95% CI: 0.02 to 0.13) at age 15. Conclusions: This longitudinal study revealed that children presenting a long sleep latency throughout childhood are at greater risk of symptoms of depression, ADHD, conduct problems, and opposition in adolescence.

Trajectories of Adolescent Media Use and Their Associations With Psychotic Experiences.

Importance: Adolescent media use is thought to influence mental health, but whether it is associated with psychotic experiences (PEs) is unclear. Objective: To examine longitudinal trajectories of adolescent media use and their associations with PEs at 23 years of age. Design, Setting, and Participants: This cohort study included participants from the Québec Longitudinal Study of Child Development (1998-2021): children who were born in Québec, Canada, and followed up annually or biennially from ages 5 months through 23 years. Data were analyzed between January 2023 and January 2024. Exposures: Participants reported their weekly amount of television viewing, video gaming, computer use, and reading at ages 12, 13, 15, and 17 years. Main Outcome and Measures: Lifetime occurrence of PEs was measured at 23 years of age. Covariables included sociodemographic, genetic, family, and childhood characteristics between ages 5 months and 12 years. Results: A total of 1226 participants were included in the analyses (713 [58.2%] female, 513 [41.8%] male). For each media type, latent class mixed modeling identified 3 group-based trajectories, with subgroups following trajectories of higher use: television viewing, 128 (10.4%); video gaming, 145 (11.8%); computer use, 353 (28.8%); and reading, 140 (11.4%). Relative to lower video gaming, higher video gaming was preceded by higher levels of mental health and interpersonal problems at age 12 years. Adjusting for these risk factors mitigated the association between higher video gaming and PEs at age 23 years. The curved trajectory of computer use (189 [15.4%] participants), characterized by increasing levels of use until age 15 years followed by a decrease, was associated with higher PEs (estimated difference, +5.3%; 95% CI, +1.5% to +9.3%) relative to lower use (684 [55.8%] participants). This association remained statistically significant after covariable adjustment. Conclusions and Relevance: This study found that longitudinal trajectories of media use during adolescence were modestly associated with PEs at age 23 years, likely reflecting the influence of shared risk factors. Understanding the environmental determinants and psychosocial functions of media use during adolescence may help better integrate digital technologies in the prevention and management of PEs.

Factors associated with physical function among people with systemic sclerosis: a SPIN cohort cross-sectional study.

OBJECTIVES: To compare physical function in systemic sclerosis (SSc, scleroderma) to general population normative data and identify associated factors. METHODS: Scleroderma Patient-centered Intervention Network Cohort participants completed the Physical Function domain of the Patient-Reported Outcomes Measurement Information System Version 2 upon enrolment. Multivariable linear regression was used to assess associations of sociodemographic, lifestyle, and disease-related variables. RESULTS: Among 2,385 participants, mean physical function T-score (43.7, SD = 8.9) was ∼2/3 of a standard deviation (SD) below the US general population (mean = 50, SD = 10). Factors associated in multivariable analysis included older age (-0.74 points per SD years, 95% CI -0.78 to -1.08), female sex (-1.35, -2.37 to -0.34), fewer years of education (-0.41 points per SD in years, -0.75 to -0.07), being single, divorced, or widowed (-0.76, -1.48 to -0.03), smoking (-3.14, -4.42 to -1.85), alcohol consumption (0.79 points per SD drinks per week, 0.45-1.14), BMI (-1.41 points per SD, -1.75 to -1.07), diffuse subtype (-1.43, -2.23 to -0.62), gastrointestinal involvement (-2.58, -3.53 to -1.62), digital ulcers (-1.96, -2.94 to -0.98), moderate (-1.94, -2.94 to -0.93) and severe (-1.76, -3.24 to -0.28) small joint contractures, moderate (-2.10, -3.44 to -0.76) and severe (-2.54, -4.64 to -0.44) large joint contractures, interstitial lung disease (-1.52, -2.27 to -0.77), pulmonary arterial hypertension (-3.72, -4.91 to -2.52), rheumatoid arthritis (-2.10, -3.64 to -0.56) and idiopathic inflammatory myositis (-2.10, -3.63 to -0.56). CONCLUSION: Physical function is impaired for many individuals with SSc and associated with multiple disease factors.

Mental health of Canadian youth: A systematic review and meta-analysis of studies examining changes in depression, anxiety, and suicide-related outcomes during the COVID-19 pandemic.

OBJECTIVES: This systematic review and meta-analysis aims to describe Canadian youth mental health during the COVID-19 pandemic, focusing on changes in anxiety and depressive symptoms and suicidality. METHODS: We searched four databases up to February 2023 for longitudinal or repeated cross-sectional studies reporting on changes in depressive and anxiety symptoms, suicidality, or related services utilization among young people under 25 years old residing in Canada during the COVID-19 pandemic. Random-effects meta-analyses were performed for studies comparing depressive and anxiety symptoms from before to during the first, second, and third COVID-19 waves (up to June 2021), and between COVID-19 waves. Other studies were described narratively. Risk of bias was assessed using an adapted Joanna Briggs Institute Checklist. SYNTHESIS: Of the 7916 records screened, 35 articles met inclusion criteria for this review. Included studies were highly heterogeneous in design, population, and type of change investigated, and many had a high risk of bias. The meta-analyses found that depressive symptoms worsened minimally from pre-pandemic to wave 1 but returned to pre-pandemic levels by wave 2. Anxiety symptoms were broadly comparable from pre-pandemic to waves 1 and 2 but worsened from waves 1 to 3 and from pre-pandemic to wave 1 for girls. The narrative review included several studies that provided inconclusive evidence of increases in services utilization. CONCLUSION: The current evidence is limited and highly heterogeneous, making it insufficient to draw definitive conclusions regarding the short- to medium-term impact of the pandemic on youth mental health in Canada. Obtaining better mental health surveillance among Canadian youth is imperative.

RéSUMé: OBJECTIFS: Cette revue systématique et méta-analyse vise à décrire la santé mentale des jeunes Canadiens pendant la pandémie de COVID-19 en ce qui concerne les changements dans les symptômes d'anxiété et de dépression et la suicidalité. MéTHODES: Nous avons cherché dans quatre bases de données, jusqu'en février 2023, des études longitudinales ou transversales répétées portant sur l'évolution des symptômes dépressifs et anxieux, de la suicidalité ou de l'utilisation des services en santé mentale chez les jeunes de moins de 25 ans résidant au Canada pendant la pandémie de COVID-19. Des méta-analyses à effets aléatoires ont été réalisées pour les études comparant les symptômes dépressifs et anxieux avant et pendant les première, deuxième et troisième vagues du COVID-19 (jusqu'en juin 2021), ainsi qu'entre les vagues de COVID-19. Les autres études ont été décrites de manière narrative. Le risque de biais a été évalué à l'aide d'une liste de contrôle adaptée du Joanna Briggs Institute. SYNTHèSE: Sur les 7 916 dossiers examinés, 35 articles répondaient aux critères d'inclusion de la présente étude. Les études retenues sont très hétérogènes en termes de conception, de population et de type de changement étudié, et un grand nombre d'entre elles présentent un risque élevé de biais. Les méta-analyses révèlent que les symptômes dépressifs se sont légèrement aggravés entre la période prépandémique et la première vague, mais qu'ils sont revenus aux niveaux prépandémiques lors de la deuxième vague. Les symptômes d'anxiété sont globalement comparables entre la période prépandémique et les vagues 1 et 2, mais se sont aggravés entre les vagues 1 et 3 et entre la période prépandémique et la vague 1 pour les filles. La revue narrative porte sur plusieurs études qui ont fourni des preuves non concluantes de l'augmentation de l'utilisation des services en santé mentale. CONCLUSION: Les données actuelles sont limitées et très hétérogènes, ce qui ne permet pas de tirer des conclusions définitives quant à l'impact à court et moyen terme de la pandémie sur la santé mentale des jeunes au Canada. Il est impératif d'améliorer la surveillance de la santé mentale des jeunes Canadiens.

Factors associated with satisfaction with social roles and activities among people with systemic sclerosis: a Scleroderma Patient-centered Intervention Network (SPIN) cohort cross-sectional study.

OBJECTIVE: The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities. METHODS: Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors. RESULTS: Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (-1.13, 95% CI -2.18 to -0.08); living in Canada (-1.33, 95% CI -2.40 to -0.26 (reference USA)) or the UK (-2.49, 95% CI -3.92 to -1.06); body mass index (-1.08 per SD, 95% CI -1.47 to -0.69); gastrointestinal involvement (-3.16, 95% CI -4.27 to -2.05); digital ulcers (-1.90, 95% CI -3.05 to -0.76); moderate (-1.62, 95% CI -2.78 to -0.45) or severe (-2.26, 95% CI -3.99 to -0.52) small joint contractures; interstitial lung disease (-1.11, 95% CI -1.97 to -0.25); pulmonary arterial hypertension (-2.69, 95% CI -4.08 to -1.30); rheumatoid arthritis (-2.51, 95% CI -4.28 to -0.73); and Sjogren's syndrome (-2.42, 95% CI -3.96 to -0.88). CONCLUSION: Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.

Association of childhood externalizing, internalizing, comorbid problems with criminal convictions by early adulthood.

Childhood externalizing problems have been linked with adult criminality. However, little is known about criminal outcomes among children with comorbid externalizing and internalizing problems. We examined the associations between profiles of behavioral problems during childhood (i.e., externalizing, internalizing, and comorbid) and criminality by early adulthood. Participants were N = 3017 children from the population-based Quebec Longitudinal Study of Kindergarten Children followed up from age 6-25. Multitrajectory modeling of teacher-rated externalizing and internalizing problems from age 6-12 years identified four distinct profiles: no/low, externalizing, internalizing, and comorbid problems. Juvenile (age 13-17) and adult (age 18-25) criminal convictions were extracted from official records. Compared to children in the no/low profile, those in the externalizing and comorbid profiles were at higher risk of having a criminal conviction, while no association was found for children in the internalizing profile. Children with comorbid externalizing and internalizing problems were most at risk of having a criminal conviction by adulthood, with a significantly higher risk when compared to children with externalizing or internalizing problems only. Similar results were found when violent and non-violent crimes were investigated separately. Specific interventions targeting early comorbid behavioral problems could reduce long-term criminality.

Perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fMRI study.

The occurrence of suicidal behaviors increases during adolescence. Hypersensitivity to negative social signals and deficits in cognitive control are putative mechanisms of suicidal behaviors, which necessitate confirmation in youths. Multidomain functional neuroimaging could enhance the identification of patients at suicidal risk beyond standard clinical measures. Three groups of adolescents (N = 96; 78% females, age = 11.6-18.1) were included: patients with depressive disorders and previous suicide attempts (SA, n = 29); patient controls with depressive disorders but without any suicide attempt history (PC, n = 35); and healthy controls (HC, n = 32). We scanned participants with 3T-MRI during social inclusion/exclusion (Cyberball Game) and response inhibition (Go-NoGo) tasks. Neural activation was indexed by the blood-oxygenation-level dependent (BOLD) of the hemodynamic response during three conditions in the Cyberball Game ("Control condition", "Social Inclusion", and "Social Exclusion"), and two conditions in Go-NoGo task ("Go" and "NoGo" blocks). ANCOVA-style analysis identified group effects across three whole-brain contrasts: 1) NoGo vs. Go, 2) Social inclusion vs. control condition, 3) Social exclusion vs. control condition. We found that SA had lower activation in the left insula during social inclusion vs. control condition compared to PC and HC. Moreover, SA compared to PC had higher activity in the right middle prefrontal gyrus during social exclusion vs. control condition, and in bilateral precentral gyri during NoGo vs. Go conditions. Task-related behavioral and self-report measures (Self-reported emotional reactivity in the Cyberball Game, response times and number of errors in the Go-NoGo Task) did not discriminate groups. In conclusion, adolescent suicidal behaviors are likely associated with neural alterations related to the processing of social perception and response inhibition. Further research, involving prospective designs and diverse cohorts of patients, is necessary to explore the potential of neuroimaging as a tool in understanding the emergence and progression of suicidal behaviors.

Emotion Dysregulation Is Associated With Increased Problem Cannabis Use Among Emerging Adults During COVID-19.

OBJECTIVE: Emerging adulthood (18-25 years) is associated with peak prevalence of cannabis use. Although population-based longitudinal studies have found little change in cannabis use among emerging adults during COVID-19, research examining changes among vulnerable subgroups is lacking. The present study examined the association between emotion dysregulation at 23 years and change in cannabis use frequency and problem cannabis use among a large sample of emerging adults, from before to during the COVID-19 pandemic. METHOD: Longitudinal data were analyzed from 1,226 emerging adults (59% female; n = 738 reported cannabis use) who completed online surveys before the pandemic (2019; age 21) and 1 year into COVID-19 (2021; age 23) as part of the Québec Longitudinal Study of Child Development. RESULTS: There was no significant overall within-person change in cannabis use outcomes during COVID-19 among the emerging adult sample. However, emotional clarity (a dimension of emotion dysregulation) at 23 years significantly moderated change in problem cannabis use during COVID-19. Namely, low emotional clarity at 23 years was associated with increased problem cannabis use (B = 0.79, 95% CI [0.23, 1.34]), whereas high emotional clarity at 23 years was associated with decreased problem cannabis use (B = -0.68, 95% CI [-1.27, -0.09]) during COVID-19, among men only. CONCLUSIONS: Findings highlight the need to consider changes in cannabis use during COVID-19 among emerging adults with elevated emotion dysregulation (and particularly, low emotional clarity among men) and reiterate the need for supports and targeted interventions to reduce cannabis use and decrease associated harms as society emerges from COVID-19.

Associations between digital media use and psychotic experiences in young adults of Quebec, Canada: a longitudinal study.

PURPOSE: Digital media use has been associated with psychotic experiences in youth from the community, but the direction of association remains unclear. We aimed to examine between- and within-person associations of digital media use and psychotic experiences in youth. METHODS: The sample included 425 participants aged 18-25 years (82.5% female) from the community, followed between May 2021 and January 2022 over 3 time points-of which 263 participants (61.9%) completed at least 2. Digital media use was self-reported as time spent daily on TV and streaming platforms, social media, and video games over the past 3 months. Psychotic experiences in the past 3 months were measured with the 15-item Community Assessment of Psychic Experiences. Associations between digital media use and psychotic experiences were estimated using a random-intercept cross-lagged panel model. RESULTS: On average, individuals who reported greater digital media use also reported higher levels of psychotic experiences (r = 0.34, 95% CI 0.15, 0.53). However, a person's variation in digital media use, relative to their personal average, was not significantly associated with subsequent variations in their levels of psychotic experiences, or vice-versa. Results were similar across TV/streaming, social media and video game use, and after adjusting for age, sex, education, sleep, physical activity, and cannabis use. CONCLUSION: Individuals with a tendency for higher levels of digital media use also had a tendency for higher levels of psychotic experiences. Understanding this association may help personalize mental health interventions for people with psychotic experiences, which may be offered digitally to promote their accessibility.

Heterogeneity in the trajectories of psychological distress among late adolescents during the COVID-19 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has constrained opportunities in social, educational and professional domains, leading to developmental challenges for adolescents initiating their transition to adulthood. Meta-analysis indicated that there was a small increase in psychological distress during the first year of the COVID-19 pandemic. However, significant heterogeneity in the psychological response to the COVID-19 pandemic was noted. Developmental antecedents as well as social processes may account for such heterogeneity. The goal of this study was to characterize trajectories of psychological distress in late adolescence during the COVID-19 pandemic. Methods: 5014 late adolescents born between 2000 and 2002 from the UK Millennium Cohort Study completed online self-reported assessments at three occasions during the first year of the COVID-19 pandemic (May 2020, September/October 2020 and February/March 2021). These surveys assessed psychological distress, loneliness, social support, family conflict, as well as other pandemic stressors. Information on developmental antecedents were obtained when cohort members were 17 years of age. Results: Four distinct trajectories class were identified. Normative class (52.13%) experienced low and decreasing levels of psychological distress, while moderately increasing class (31.84%) experienced a small, but significant increase in distress over time and increasing class (8.75%) exhibited a larger increase in distress after the first wave of the pandemic. Inverted U-shaped class (7.29%) experienced elevated psychological distress during the first wave of the pandemic, followed by a decrease in distress in subsequent waves of the pandemic. Larger longitudinal increases in loneliness were noted among individuals in the elevated distress trajectory, compared to other trajectories. Pre-pandemic psychopathology was associated with elevated distress early in the pandemic. Conclusions: The largest trajectory showed low and declining psychological distress, highlighting the resilience of the majority of late adolescents. However, a subgroup of adolescents experienced large increases in psychological distress, identifying a group of individuals more vulnerable to pandemic-related stress.

Increased urban greenspace in childhood associated with lower inattention deficit among adolescents.

PURPOSE: There is a growing interest in assessing the benefits of exposure to urban greenspace on mental health due to the increased urbanization of youth and concerns for their mental health. We investigated the prospective associations of residential greenspace in childhood and mental health in adolescence. Use of a well-characterized birth cohort permitted adjustment for a range of potential confounding factors including family and neighborhood characteristics in addition to prior mental health problems, and exploration of moderation effects by sex and family socioeconomic status. METHODS: We analyzed longitudinal data collected from 742 urban-dwelling participants of the Quebec Longitudinal Study of Children Development. The Normalized Difference Vegetation Index (NDVI) within 250, 500, and 1000 m buffer zones surrounding the home residence was used to indicate childhood exposure to greenspace. Six self-reported mental health problems at 15/17 years were examined using the Mental Health and Social Inadaptation questionnaire: inattention, hyperactivity/impulsivity, conduct, depression, anxiety, and suicidal ideation. RESULTS: Childhood urban greenspace was associated with lower inattention problems in both females and males. We observed a 0.14 reduced standard deviation (SD) (ß = - 0.14, SE = 0.05, p < 0.01) in relation to an interquartile range (IQR) increase of NDVI (0.15) at the 250 m buffer zone, and similar results were found in 500 m and 1000 m buffer zones. These associations only slightly attenuated after adjustment for individual (sex, childhood mental health), family (family SES, maternal age at birth, parental mental health, family composition), and neighborhood (material and social deprivation) characteristics (ß = - 0.13, SE = 0.06, p = 0.03). No association was found for other mental health problems, and no moderation associations of sex or family socioeconomic status were observed. CONCLUSION:  These findings suggest that increasing residential greenspace in cities may be associated with modest benefits in attentional capacities in youth, necessitating further research to elucidate the underlying mechanisms.

Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function.

PML nuclear bodies (NB) are disrupted in PML-RARA-driven acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) cures 70% of patients with APL, driving PML-RARA degradation and NB reformation. In non-APL cells, arsenic binding onto PML also amplifies NB formation. Yet, the actual molecular mechanism(s) involved remain(s) elusive. Here, we establish that PML NBs display some features of liquid-liquid phase separation and that ATO induces a gel-like transition. PML B-box-2 structure reveals an alpha helix driving B2 trimerization and positioning a cysteine trio to form an ideal arsenic-binding pocket. Altering either of the latter impedes ATO-driven NB assembly, PML sumoylation, and PML-RARA degradation, mechanistically explaining clinical ATO resistance. This B2 trimer and the C213 trio create an oxidation-sensitive rheostat that controls PML NB assembly dynamics and downstream signaling in both basal state and during stress response. These findings identify the structural basis for arsenic targeting of PML that could pave the way to novel cancer drugs. SIGNIFICANCE: Arsenic curative effects in APL rely on PML targeting. We report a PML B-box-2 structure that drives trimer assembly, positioning a cysteine trio to form an arsenic-binding pocket, which is disrupted in resistant patients. Identification of this ROS-sensitive triad controlling PML dynamics and functions could yield novel drugs. See related commentary by Salomoni, p. 2505. This article is featured in Selected Articles from This Issue, p. 2489.

Psychosocial interventions for the prevention of self-harm repetition: protocol for a systematic review and network meta-analysis.

INTRODUCTION: Suicide is an important public health problem. Providing evidence-based psychosocial interventions to individuals presenting with self-harm is recognised as an important suicide prevention strategy. Therefore, it is crucial to understand which intervention is most effective in preventing self-harm repetition. We will evaluate the comparative efficacy of psychosocial interventions for the prevention of self-harm in adults. METHODS AND ANALYSIS: We will perform a systematic review and network meta-analysis (NMA) of randomised controlled trials (RCTs) testing psychosocial interventions for the prevention of self-harm repetition. We will include RCTs in adults (mean age: 18 years or more) who presented with self-harm in the 6 months preceding enrolment in the trial. Interventions will be categorised according to their similarities and underpinning theoretical approaches (eg, cognitive behavioural therapy, case management). A health sciences librarian will update and adapt the search strategy from the most recent Cochrane pairwise systematic review on this topic. The searches will be performed in MEDLINE (Ovid), Embase (Ovid), PsycInfo (Ovid), CINAHL (EBSCO), Cochrane Central (Wiley), Cochrane Protocols (Wiley), LILACS and PSYNDEX from 1 July 2020 (Cochrane review last search date) to 1 September 2023. The primary efficacy outcome will be self-harm repetition. Secondary outcomes will include suicide mortality, suicidal ideation and depressive symptoms. Retention in treatment (ie, drop-outs rates) will be analysed as the main acceptability outcome. Two reviewers will independently assess the study eligibility and risk of bias (using RoB-2). An NMA will be performed to synthesise all direct and indirect comparisons. Ranked forest plots and Vitruvian plots will be used to represent graphically the results of the NMA. Credibility of network estimates will be evaluated using Confidence in NMA (CINeMA). ETHICS AND DISSEMINATION: As this is the protocol for an aggregate-data level NMA, ethical approval will not be required. Results will be disseminated at national/international conferences and in peer-review journals. TRIAL REGISTRATION NUMBER: CRD42021273057.

Derivation of probable child maltreatment indicators using prospectively recorded information between 5 months and 17 years in a longitudinal cohort of Canadian children.

BACKGROUND: Both prospective and retrospective measures of child maltreatment predict mental and physical health problems, despite their weak concordance. Research remains largely based on retrospective reports spanning the entire childhood due to a scarcity of prospectively completed measures targeting maltreatment specifically. OBJECTIVE: We developed a prospective index of child maltreatment in the Québec Longitudinal Study of Child Development (QLSCD) using prospective information collected from ages 5 months to 17 years and examined its concordance with retrospective maltreatment. PARTICIPANTS AND SETTING: The QLSCD is an ongoing population-based cohort that includes 2,120 participants born from 1997-1998 in the Canadian Province of Quebec. METHODS: As the QLSCD did not have maltreatment as a focal variable, we screened 29,600 items completed by multiple informants (mothers, children, teachers, home observations) across 14 measurement points (5 months-17 years). Items that could reflect maltreatment were first extracted. Indicators were derived across preschool, school-age and adolescence periods and by the end of childhood and adolescence, including presence (yes/no), chronicity (re-occurrence), extent of exposure and cumulative maltreatment. Two maltreatment experts reviewed these items for inclusion and determined cut-offs for possible child maltreatment (n=251 items). Retrospective maltreatment was self-reported at 23 years. RESULTS: Across all developmental periods, the presence of maltreatment was as follows: physical abuse (16.3-21.8%), psychological abuse (3.3-21.9%), emotional neglect (20.4-21.6%), physical neglect (15.0-22.3%), supervisory neglect (25.8-44.9%), family violence (4.1-11.2%) and sexual abuse (9.5% in adolescence only). The degree of concordance between prospective and retrospective reports for each type of maltreatment was weak (.038-.110), yet significant (ps<.01), except for emotional neglect (p=.148). CONCLUSIONS: In addition to the many future research opportunities offered by these prospective indicators of maltreatment, this study offers a roadmap to researchers wishing to undertake a similar task.

Methods and results of studies on reporting guideline adherence are poorly reported: a meta-research study.

OBJECTIVES: We investigated recent meta-research studies on adherence to four reporting guidelines to determine the proportion that provided (1) an explanation for how adherence to guideline items was rated and (2) results from all included individual studies. We examined conclusions of each meta-research study to evaluate possible repetitive and similar findings. STUDY DESIGN AND SETTING: A cross-sectional meta-research study. MEDLINE (Ovid) was searched on July 5, 2022 for studies that used any version of the Consolidated Standards of Reporting Trials, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Standards for the Reporting of Diagnostic Accuracy Studies, or Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines or their extensions to evaluate reporting. RESULTS: Of 148 included meta-research studies published between August 2020 and June 2022, 14 (10%, 95% confidence interval [CI] 6%-15%) provided a fully replicable explanation of how they coded the adherence ratings and 49 (33%, 95% CI 26%-41%) completely reported individual study results. Of 90 studies that classified reporting as adequate or inadequate in the study abstract, six (7%, 95% CI 3%-14%) concluded that reporting was adequate, but none of those six studies provided information on how items were coded or provided item-level results for included studies. CONCLUSION: Almost all included meta-research studies found that reporting in health research is suboptimal. However, few of these reported enough information for verification or replication.

Depression, anxiety, and suicidal ideation in a population-based cohort of young adults before and during the first 12 months of the COVID-19 pandemic in Canada.

OBJECTIVES: Findings from a birth cohort study indicated that the mental health of young adults had not worsened during the first wave of the COVID-19 pandemic, compared to 2018. This study examined longitudinal changes in mental health between March 2018 and June 2021 in the context of protracted public health mitigation measures about 12 months after the onset of the pandemic. METHODS: Participants from the Quebec Longitudinal Study of Child Development (n = 2120 at inception; n = 1461 during the COVID-19 pandemic), a population-based cohort of individuals born in 1997/1998, reported on their depressive and anxiety symptoms as well as suicidal ideation prior to the pandemic in 2018 (age 20), and during the pandemic in the summer of 2020 (age 22) and spring of 2021 (age 23). RESULTS: Depressive (Cohen's d = 0.15 [95% CI: 0.09 to 0.20]) and anxiety (Cohen's d = 0.33 [95% CI: 0.27 to 0.39]) symptoms increased between 2018 and 2021 for both males and females, but suicidal ideation did not change. There was also a significant increase in moderate to severe depressive (31.7% to 36.3%) and anxiety (14.7% to 24.8%) symptoms from 2018 to 2021. Youth who were students, those who were experiencing financial stress, food insecurity, and loneliness, and those without pre-existing poor mental health experienced the largest increase in depressive and anxiety symptoms over time. CONCLUSION: These findings highlight the mental health burden experienced by young adults during the COVID-19 pandemic, highlighting the need for preventive services and continued longitudinal follow-ups of these youths.

RéSUMé: OBJECTIFS: Les résultats d'une étude de cohorte de naissance ont indiqué que la santé mentale des jeunes adultes ne s'était pas détériorée au cours de la première vague de la pandémie de la COVID-19, en comparaison à 2018. La présente étude examine maintenant les changements longitudinaux de la santé mentale entre mars 2018 et juin 2021, dans le contexte de mesures prolongées de santé publique, environ 12 mois après le début de la pandémie. MéTHODES: Les participants de l'Étude longitudinale du développement des enfants du Québec (n = 2120 à la création; n = 1461 pendant la pandémie de COVID-19), une cohorte basée sur la population de personnes nées en 1997­98, ont rapporté leurs symptômes de dépression et d'anxiété ainsi que leurs idéations suicidaires avant la pandémie en 2018 (20 ans), pendant la pandémie à l'été 2020 (22 ans) ainsi qu'au printemps 2021 (23 ans). RéSULTATS: Les symptômes de dépression (d de Cohen = 0,15 [95% IC: 0,09 à 0,20]) et d'anxiété (d de Cohen = 0,33 [95% IC: 0,27 à 0,39]) ont augmenté entre 2018 et 2021 chez les hommes et les femmes, mais les idéations suicidaires n'ont pas changé. Une augmentation significative des symptômes dépressifs modérés à sévères (31,7 % à 36,3 %) et des symptômes d'anxiété (14,7 % à 24,8 %) a également été observée entre 2018 et 2021. Les jeunes qui étaient étudiants, ceux qui rapportaient un stress financier, de l'insécurité alimentaire et de la solitude, ainsi que ceux qui avaient une bonne santé mentale en prépandémie, ont connu la plus forte augmentation des symptômes de dépression et d'anxiété au fil du temps. CONCLUSION: Ces résultats mettent en évidence l'impact de la pandémie de la COVID-19 sur la santé mentale des jeunes adultes, et soulignent la nécessité de mettre en place des services de prévention et de poursuivre le suivi longitudinal de ces jeunes.

Suicidal ideation following self-reported COVID-19-like symptoms or serology-confirmed SARS-CoV-2 infection in France: A propensity score weighted analysis from a cohort study.

BACKGROUND: A higher risk of suicidal ideation associated with self-report of Coronavirus Disease 2019 (COVID-19)-like symptoms or COVID-19 infection has been observed in cross-sectional studies, but evidence from longitudinal studies remains limited. The aims of this study were 2-fold: (1) to explore if self-reported COVID-19-like symptoms in 2020 were associated with suicidal ideation in 2021; (2) to explore if the association also existed when using a biological marker of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in 2020. METHODS AND FINDINGS: A total of 52,050 participants from the French EpiCov cohort were included (median follow-up time = 13.7 months). In terms of demographics, 53.84% were women, 60.92% were over 45 years old, 82.01% were born in mainland France from parents born in mainland France, and 59.38% completed high school. COVID-19-like symptoms were defined as participant report of a sudden loss of taste/smell or fever alongside cough, shortness of breath, or chest oppression, between February and November 2020. Symptoms were self-reported at baseline in May 2020 and at the first follow-up in Autumn 2020. Serology-confirmed SARS-CoV-2 infection in 2020 was derived from Spike protein ELISA test screening in dried-blood-spot samples. Samples were collected from October 2020 to March 2021, with 94.4% collected in 2020. Suicidal ideation since December 2020 was self-reported at the second follow-up in Summer 2021. Associations of self-reported COVID-19-like symptoms and serology-confirmed SARS-CoV-2 infection in 2020 with suicidal ideation in 2021 were ascertained using modified Poisson regression models, weighted by inverse probability weights computed from propensity scores. Among the 52,050 participants, 1.68% [1.54% to 1.82%] reported suicidal ideation in 2021, 9.57% [9.24% to 9.90%] had a serology-confirmed SARS-CoV-2 infection in 2020, and 13.23% [12.86% to 13.61%] reported COVID-19-like symptoms in 2020. Self-reported COVID-19-like symptoms in 2020 were associated with higher risks of later suicidal ideation in 2021 (Relative Riskipw [95% CI] = 1.43 [1.20 to 1.69]), while serology-confirmed SARS-CoV-2 infection in 2020 was not (RRipw = 0.89 [0.70 to 1.13]). Limitations of this study include the use of a single question to assess suicidal ideation, the use of self-reported history of mental health disorders, and limited generalizability due to attrition bias. CONCLUSIONS: Self-reported COVID-19-like symptoms in 2020, but not serology-confirmed SARS-CoV-2 infection in 2020, were associated with a higher risk of subsequent suicidal ideation in 2021. The exact role of SARS-CoV-2 infection with respect to suicide risk has yet to be clarified. Including mental health resources in COVID-19-related settings could encourage symptomatic individuals to care for their mental health and limit suicidal ideation to emerge or worsen.