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1.
JCPP Adv ; 4(2): e12222, 2024 Jun.
Article En | MEDLINE | ID: mdl-38827976

Background: Hyperactivity and inattention, the symptoms of ADHD, are marked by high levels of heritability and intergenerational transmission. Two distinct pathways of genetic intergenerational transmission are distinguished: direct genetic transmission when parental genetic variants are passed to the child's genome and genetic nurture when the parental genetic background contributes to the child's outcomes through rearing environment. This study assessed genetic contributions to hyperactivity and inattention in childhood through these transmission pathways. Methods: The sample included 415 families from the Quebec Newborn Twin Study. Twins' hyperactivity and inattention were assessed in early childhood by parents and in primary school by teachers. The polygenic scores for ADHD (ADHD-PGS) and educational attainment (EA-PGS) were computed from twins' and parents' genotypes. A model of intergenerational transmission was developed to estimate (1) the contributions of parents' and children's PGS to the twins' ADHD symptoms and (2) whether these variances were explained by genetic transmission and/or genetic nurture. Results: ADHD-PGS explained up to 1.6% of the variance of hyperactivity and inattention in early childhood and primary school. EA-PGS predicted ADHD symptoms at both ages, explaining up to 1.6% of the variance in early childhood and up to 5.5% in primary school. Genetic transmission was the only significant transmission pathway of both PGS. The genetic nurture channeled through EA-PGS explained up to 3.2% of the variance of inattention in primary school but this association was non-significant. Conclusions: Genetic propensities to ADHD and education predicted ADHD symptoms in childhood, especially in primary school. Its intergenerational transmission was driven primarily by genetic variants passed to the child, rather than by environmentally mediated parental genetic effects. The model developed in this study can be leveraged in future research to investigate genetic transmission and genetic nurture while accounting for parental assortative mating.

2.
Psychoneuroendocrinology ; 166: 107072, 2024 May 08.
Article En | MEDLINE | ID: mdl-38733756

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.

3.
JAMA Psychiatry ; 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38598210

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.

4.
Compr Psychoneuroendocrinol ; 18: 100234, 2024 May.
Article En | MEDLINE | ID: mdl-38660593

Background: Hair has become an increasingly valuable medium to investigate the association between chronic stress, stable differences in systemic cortisol secretion and later health. Assessing cortisol in hair has many advantages, notably its non-invasive and retrospective nature, the need for a single biospecimen and convenient storage until analysis. However, few studies offered empirical evidence documenting the long-term temporal stability of hair cortisol concentration (HCC) prior to analysis, especially in humans. Yet, knowing how long hair samples can be stored without compromising the accuracy of cortisol measurement is of crucial importance when planning data collection and analysis. This study examined the stability of HCC in hair samples assayed twice, five years apart. Methods: We randomly selected from a larger distribution of HCC measured in 17-year-old participants 39 hair samples to be reanalyzed five years later, under the same general conditions. Samples were assayed in duplicate using a luminescence immunoassay and compared with the original HCC using the Lin's concordance correlation coefficient (CCC), Bland-Altman plot analysis and Wilcoxon rank test. Results: Findings indicated a good concordance and temporal stability between the two samples assayed five years apart (CCC [95% confidence interval] = 0.84 [0.72-0.91]), although a small decrease in HCC was noted 5 years later (8.4% reduction, p = 0.001). Conclusion: Our study confirms that hair samples, when stored at room temperature and away from sunlight, can be assayed for at least five years without risking a loss of precision in HCC measurement.

5.
Nephron ; 2024 Apr 24.
Article En | MEDLINE | ID: mdl-38657576

BACKGROUND: Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). SUMMARY: This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in Phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the Phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D [25(OH)D] and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled Phase 3 per-protocol populations, 74% of the ERC cohort were up-titrated to 60 µg/day after 12 weeks at 30 µg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. KEY MESSAGES: These data establish a 'continuum' of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

6.
Front Psychol ; 15: 1303063, 2024.
Article En | MEDLINE | ID: mdl-38425559

Introduction: Firefighters face elevated risks of common mental health issues, with distress rates estimated at around 30%, surpassing those of many other occupational groups. While exposure to potentially traumatic events (PTEs) is a well-recognized risk factor, existing research acknowledges the need for a broader perspective encompassing multidimensional factors within the realm of occupational stress. Furthermore, this body of evidence heavily relies on cross-sectional studies. This study adopts an intensive longitudinal approach to assess psychological distress and its determinants among firefighters. Methods: Participants were recruited from 67 fire stations in Montreal, Canada, meeting specific criteria: full-time employment, smartphone ownership, and recent exposure to at least one PTE, or first responder status. Subjects underwent a telephone interview and were directed to use an app to report depressive, post-traumatic, and generalized anxiety symptoms every 2 weeks, along with work-related stressors, social support, and coping styles. Analyses involved 274 participants, distinguishing between those exceeding clinical thresholds in at least one distress measure (the "distressed" subgroup) and those deemed "resilient." The duration and onset of distress were computed for the distressed group, and linear mixed models were employed to evaluate determinants for each psychological distress variable. Results: Clinical psychological distress was observed in 20.7% of participants, marked by depressive, post-traumatic, and anxiety symptoms, often within the first 4-week reference period. Contextual factors (operational climate, social support, solitude) and individual factors (coping style, solitude and lifetime traumatic events in private life) exhibited more significant impacts on psychological distress than professional pressures within the firefighters' work environment. Discussion: This study reports lower rates of psychological distress than previous research, possibly attributable to sample differences. It highlights that reported symptoms often represent a combined and transient layer of distress rather than diagnosable mental disorders. Additionally, determinants analysis underscores the importance of interpersonal relationships and coping mechanisms for mental health prevention interventions within this worker group. The findings carry implications for the development of prevention and support programs for firefighters and similar emergency workers.

7.
Psychiatry Res ; 332: 115718, 2024 Feb.
Article En | MEDLINE | ID: mdl-38198857

The Signature Biobank is a longitudinal repository of biospecimen, psychological, sociodemographic, and diagnostic data that was created in 2012. The Signature Consortium represents a group of approximately one hundred Quebec-based transdisciplinary clinicians and research scientists with various expertise in the field of psychiatry. The objective of the Signature Biobank is to investigate the multi-faceted underpinnings of psychiatric disorders among patients in crisis. The Signature Consortium is expanding and includes new active members that seek to highlight the contributions made by Signature Biobank since its inception. This article details our research protocol, directions, and summarizes contributions. To date, we have collected biological samples (n = 1,986), and questionnaire data (n = 2,085) from psychiatric emergency patients of the Institut universitaire en santé mentale de Montréal (Quebec, Canada), with a large proportion from whom both data types were collected (n = 1,926). In addition to this, a subsample of patients was followed-up at hospital discharge, and two additional outpatient clinic appointments (n = 958 with at least one follow-up). In addition, a socio-demographically matched comparison group of individuals who were not hospitalized for psychiatric disorders (n = 149) was recruited from the surrounding catchment area. To summarize, a systematic review of the literature shows that the Signature Biobank has contributed to better characterizing psychiatric comorbidities, biological profiles, and psychosocial functioning across some of the most common psychiatric disorders, including psychosis, mood, anxiety, and substance use disorders. The Signature Biobank is now one of the world's largest repositories of data collected from patients receiving care at a psychiatric emergency unit.


Psychiatry , Psychotic Disorders , Substance-Related Disorders , Humans , Biological Specimen Banks , Comorbidity , Psychotic Disorders/diagnosis
8.
Am J Nephrol ; 2024 Jan 22.
Article En | MEDLINE | ID: mdl-38253036

Black and African American (AA) people are over-represented in the kidney failure population; therefore, the safety and efficacy of difelikefalin in Black/AA patients was evaluated. This was a post hoc, pooled exploratory subgroup analysis of the Phase 3 KALM-1 and -2 studies. Patients undergoing hemodialysis (HD) who had moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) at enrollment were stratified into self-reported Black/AA or White subgroups. Patients were randomized (1:1) to receive intravenous (IV) difelikefalin 0.5 µg/kg or placebo for 12 weeks. Difelikefalin efficacy was assessed with validated patient-reported outcome questionnaires: 24-hour Worst Itch Numerical Rating Scale (WI-NRS), 5-D itch, and Skindex 10. There were 249 (29.3%) patients from the KALM studies that self-identified as Black/AA (n=135 difelikefalin; n=114 placebo). Clinically meaningful (≥3-point) reduction in WI-NRS score was achieved by 47.9% of Black/AA patients with difelikefalin versus 24.6% with placebo (P<0.001). More Black/AA patients achieved a ≥5-point 5-D itch total improvement (54.9% vs 35.7%; P=0.013) and a ≥15-point Skindex-10 score improvement with difelikefalin versus placebo (49.0% vs 28.9%; P=0.006) compared with White patients. Incidence of treatment-emergent adverse events (TEAEs) was higher for Black/AA patients (difelikefalin: 78.5%; placebo: 70.8%) versus White patients (difelikefalin: 64.8%; placebo: 61.8%). In this post hoc analysis, difelikefalin was efficacious in the Black/AA population and had an acceptable safety profile.

9.
Patient ; 17(2): 203-213, 2024 Mar.
Article En | MEDLINE | ID: mdl-38196014

OBJECTIVE: Chronic kidney disease-associated pruritus (CKD-aP) can have a substantial negative impact on health-related quality of life (HRQoL), including an increased risk of depression, anxiety and sleep disturbance. This trial aimed to assess the impact of intravenous difelikefalin on HRQoL in haemodialysis patients with moderate-to-severe CKD-aP. METHODS: Post hoc analysis of an open-label, multicentre, single-arm intervention trial assessed pruritus severity and HRQoL at baseline and at 12 weeks of difelikefalin treatment using Worst Itching Intensity Numerical Rating Scale (WI-NRS), Sleep Quality Numeric Rating Scale (SQ-NRS), 5-D itch scale, Skindex-10 scale, EQ-5D-5L with Pruritus Bolt-On (EQ-PSO). RESULTS: A total of 222 patients received ≥ 1 dose of difelikefalin, and 197 patients completed 12 weeks of difelikefalin treatment. Clinically meaningful changes from baseline to 12 weeks were observed in all disease-specific measures: 73.7% of patients achieved a ≥ 3-point reduction in the weekly mean of 24 h WI-NRS scores and 66% of patients experienced ≥ 3-point improvements in SQ-NRS scores. Improvements were also observed in all Skindex-10 scale and 5-D itch scale domain scores. The percentage of patients reporting no problems in all EQ-PSO domains increased from 1.4 to 24.7% (p < 0.001), respectively. Patients' generic HRQoL EQ-5D-5L mean utility and EQ-5D visual analogue scale scores increased from baseline to 12 weeks: mean changes 0.04 (p = 0.001) and 2.8 (p = 0.046), respectively. CONCLUSIONS: Patients undergoing haemodialysis with moderate-to-severe CKD-aP receiving difelikefalin reported experiencing clinically meaningful improvements in both their pruritus symptoms and itch-related QoL. CLINICALTRIALS: gov registration number, NCT03998163; first submitted, 7 May 2019.


Piperidines , Quality of Life , Renal Insufficiency, Chronic , Humans , Pruritus/drug therapy , Pruritus/etiology , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy
10.
Soc Psychiatry Psychiatr Epidemiol ; 59(1): 65-75, 2024 Jan.
Article En | MEDLINE | ID: mdl-37516683

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.


Psychotic Disorders , Adolescent , Humans , Female , Young Adult , Adult , Male , Longitudinal Studies , Psychotic Disorders/psychology , Quebec/epidemiology , Internet , Mental Health
11.
J Child Psychol Psychiatry ; 65(3): 298-307, 2024 Mar.
Article En | MEDLINE | ID: mdl-37795803

BACKGROUND: Exposure to socioeconomic adversity is hypothesized to impact hypothalamic-pituitary-adrenal (HPA) axis activity and cortisol secretion, but existing evidence is inconsistent. Yet, few studies have investigated this association using a developmental approach that considers potential protective contextual factors. This study examined the role of stability and changes in family socioeconomic status (SES) in the prediction of multiple cortisol indicators and tested whether social support moderated these associations. METHODS: Participants were part of a population-based sample of twin pairs recruited at birth. Family SES was assessed in early childhood (ages 0-5) and mid-adolescence (age 14). Social support was assessed at ages 14 and 19. Diurnal cortisol (n = 569) was measured at age 14 at awakening, 30 min later, in the afternoon and evening over four non-consecutive days. Hair cortisol concentration (HCC, n = 704) was measured at age 19. All data were collected before the pandemic and multilevel regression models were conducted to account for the nested data structure. RESULTS: Youth exposed to lower family SES levels in childhood and mid-adolescence had a flatter diurnal slope and higher HCC compared with those who experienced upward socioeconomic mobility in mid-adolescence. Contrastingly, mid-adolescence SES showed no association with the diurnal slope or HCC for youth from higher-SES households in early childhood. Moreover, youth raised in higher-SES families in early childhood had a higher CAR in mid-adolescence if they reported greater social support in mid-adolescence. Social support also moderated the SES-cortisol association in mid-adolescence, with higher-SES youth showing higher awakening cortisol secretion when reporting more social support. CONCLUSIONS: Our findings support the hypothesis that early socioeconomic adversity sensitizes HPA axis activity to later socioeconomic disadvantage, which may bear consequences for socioemotional and behavioral functioning.


Hydrocortisone , Hypothalamo-Hypophyseal System , Infant, Newborn , Humans , Adolescent , Child, Preschool , Young Adult , Adult , Stress, Psychological , Pituitary-Adrenal System , Social Class , Hair/chemistry , Saliva/chemistry , Social Support , Circadian Rhythm
12.
Environ Health Perspect ; 131(12): 125001, 2023 Dec.
Article En | MEDLINE | ID: mdl-38088579

BACKGROUND: Cancer hazard identification is critical to informing decisions on preventive actions. However, the influence of cancer hazard assessments on the creation of health-protective regulations is poorly understood. Although prior studies have measured the health and economic benefits of regulatory actions in general, we are not aware of efforts to explicitly study the influence of cancer hazard identification on policy decisions in the United States. OBJECTIVES: In this commentary, we present an approach to examine whether formal identification of a substance as a human carcinogen may prompt a regulatory action to reduce exposure to carcinogens and enhance public health. Further, we discuss the broader implications of cancer hazard identification on policy decision-making, including identifying gaps and providing recommendations. METHODS: Using the Report on Carcinogens (RoC) as a test case, we systematically searched U.S. federal and state databases for notices of regulations mentioning the RoC from 1995 to 2023. For each regulation, we extracted information on the carcinogen(s) regulated, the regulatory agency, the regulatory purpose, the economic sector exposure sources, and the analyzed public health benefits and costs. We created a publicly available, web-based interactive tool to visualize the data. DISCUSSION: U.S. regulatory agencies have been using cancer hazard evaluations, such as the RoC, for decades to inform public health policy actions to prevent or mitigate cancer risks. Specifically, nonregulatory cancer hazard assessments have been used to prioritize chemical evaluations, support regulatory-based assessments, and trigger regulatory action. Our approach showed that assessing the influence of cancer hazard identification on science-based public health policies is feasible, informative, and needed, and our study is a first step in this direction. We recommend expanding this approach to other cancer and noncancer hazard assessments to ultimately inform our understanding of the influence of hazard classifications on policymaking. https://doi.org/10.1289/EHP12681.


Neoplasms , Public Health , Humans , Carcinogens/toxicity , Neoplasms/chemically induced , Neoplasms/epidemiology , Policy , United States/epidemiology
13.
Environ Sci Technol ; 57(48): 19202-19213, 2023 Dec 05.
Article En | MEDLINE | ID: mdl-37931007

We assessed phthalate-hormone associations in 382 pregnant women of the new-generation SEPAGES cohort (2014-2017, France) using improved exposure and outcome assessments. Metabolites from seven phthalate compounds and the replacement di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) were measured in within-subject pools of repeated urine samples collected at the second and third pregnancy trimesters (≈21 samples/trimester). Metabolites from five steroid hormones were measured in maternal hair samples collected at delivery, reflecting cumulative levels over the previous weeks to months. Adjusted linear regression and Bayesian weighted quantile sum (BWQS) mixture models were performed. Each doubling in third-trimester urinary mono-benzyl phthalate (MBzP) concentrations was associated with an average increase of 13.3% (95% CI: 2.65, 24.9) for ∑cortisol, 10.0% (95% CI: 0.26, 20.7) for ∑cortisone, 17.3% (95% CI: 1.67, 35.4) for 11-dehydrocorticosterone, and 16.2% (95% CI: 2.20, 32.1) for testosterone, together with a suggestive 10.5% (95% CI: -1.57, 24.1) increase in progesterone levels. Each doubling in second-trimester urinary di-isononyl phthalate (DiNP) concentrations was inversely associated with testosterone levels (-11.6%; 95% CI: -21.6, -0.31). For most hormones, a nonsignificant trend toward a positive phthalate mixture effect was observed in the third but not in the second trimester. Our study showed that exposure to some phthalate metabolites, especially MBzP, may affect adrenal and reproductive hormone levels during pregnancy.


Environmental Pollutants , Phthalic Acids , Prenatal Exposure Delayed Effects , Humans , Female , Pregnancy , Bayes Theorem , Phthalic Acids/metabolism , Steroids , Testosterone , Hair/metabolism , Environmental Exposure , Maternal Exposure
14.
Article En | MEDLINE | ID: mdl-37968132

BACKGROUND: Poor sleep quality is associated with increased mortality and lower quality of life in patients with chronic kidney disease-associated pruritus (CKD-aP). Difelikefalin reduces itch in patients with CKD-aP undergoing haemodialysis. This post hoc analysis of Phase 3 studies (3105 and the pooled dataset from KALM-1 and KALM-2) evaluated whether itch reduction in CKD-aP improved sleep quality. METHODS: Itch intensity was assessed in patients undergoing haemodialysis, who had moderate-to-severe CKD-aP treated with intravenous difelikefalin (0.5 µg/kg, three times weekly) (N = 222, Study 3105; N = 426, KALM-1/-2) or placebo (N = 425, KALM-1/-2) for 12 weeks, using the Worst Itch Intensity Numerical Rating Scale (WI-NRS). Sleep quality was assessed using the sleep disability question of the 5-D itch scale (5­D SDQ) in all studies and, in Study 3105, with the Sleep Quality Numeric Rating Scale (SQ-NRS). RESULTS: Greater improvements in sleep quality were observed in patients with ≥ 3-point, versus < 3-point WI-NRS improvement using SQ-NRS in Study 3105 (mean [95% confidence interval]: -5.2 [-5.6, -4.8] vs -1.5 [-2.0, -1.0]) and 5-D SDQ in KALM-1/-2 (-1.8 [-2.1, -1.6] vs -0.8 [-1.1, -0.4]). SQ-NRS and WI-NRS scores correlated strongly at baseline and Week 12 in Study 3105 (Spearman correlation coefficient: 0.77 and 0.84, respectively). Correlations were also observed between 5-D SDQ and WI-NRS scores in Study 3105 and KALM­1/­2. CONCLUSIONS: In patients undergoing haemodialysis with moderate-to-severe CKD-aP, itch reduction with intravenous difelikefalin was associated with improved sleep quality. As disturbed sleep may contribute to mortality and morbidity in CKD-aP, difelikefalin may help to address a major clinical burden by improving sleep quality, secondary to itch relief.

15.
Article En | MEDLINE | ID: mdl-37837487

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.

16.
Child Abuse Negl ; 143: 106247, 2023 09.
Article En | MEDLINE | ID: mdl-37276658

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.


Child Abuse , Adolescent , Humans , Child , Child, Preschool , Longitudinal Studies , Retrospective Studies , Prospective Studies , Canada/epidemiology , Child Abuse/psychology
17.
PLoS One ; 18(5): e0285263, 2023.
Article En | MEDLINE | ID: mdl-37146008

Both common pain and anxiety problems are widespread, debilitating and often begin in childhood-adolescence. Twin studies indicate that this co-occurrence is likely due to shared elements of risk, rather than reciprocal causation. A joint genome-wide investigation and pathway/network-based analysis of adolescent anxiety and pain problems can identify genetic pathways that subserve shared etiopathogenetic mechanisms. Pathway-based analyses were performed in the independent samples of: The Quebec Newborn Twin Study (QNTS; 246 twin pairs and 321 parents), the Longitudinal Study of Child Development in Quebec (QLSCD; n = 754), and in the combined QNTS and QLSCD sample. Multiple suggestive associations (p<1×10-5), and several enriched pathways were found after FDR correction for both phenotypes in the QNTS; many nominally-significant enriched pathways overlapped between pain problems and anxiety symptoms (uncorrected p<0.05) and yielded results consistent with previous studies of pain or anxiety. The QLSCD and the combined QNTS and QLSCD sample yielded similar findings. We replicated an association between the pathway involved in the regulation of myotube differentiation (GO:0010830) and both pain and anxiety problems in the QLSDC and the combined QNTS and QLSCD sample. Although limited by sample size and thus power, these data provide an initial support to conjoint molecular investigations of adolescent pain and anxiety problems. Understanding the etiology underlying pain and anxiety co-occurrence in this age range is relevant to address the nature of comorbidity and its developmental pathways, and shape intervention. The replication across samples implies that these effects are reliable and possess external validity.


Anxiety Disorders , Anxiety , Humans , Anxiety/genetics , Anxiety Disorders/epidemiology , Anxiety Disorders/genetics , Longitudinal Studies , Pain , Phenotype
18.
BMC Public Health ; 23(1): 236, 2023 02 03.
Article En | MEDLINE | ID: mdl-36737725

BACKGROUND: This article outlines the protocol for a trial to test the effectiveness of a nature-based intervention called Open Sky School to reduce mental health problems among elementary school children. Experimental studies show that contact with nature (e.g. walks in parks) improve mental health. A growing number of teachers have been applying outdoor education within the regular school curriculum and evidence suggests that such teaching methods could improve students' mental health but a randomized controlled trial has never been conducted. METHODS: A two-arm clustered randomized controlled trial will be conducted in elementary schools across Québec, Canada. Following informed consent by teachers, parents and students, schools will be randomly assigned 1:1 to the intervention or the control group with a total of 2500 5-6th grade students and 100 teachers expected to participate. The intervention will take place outdoors in a green-space (2 h per week for 12 weeks) and include a toolkit of 30 activities to foster well-being (e.g. mindfulness) and academic competencies (e.g. mathematics). Questionnaires will be administered to teachers and students before, immediately after and 3 months after the intervention. The primary outcome will be reductions of mental health problems in children from pre-to-post test (Social Behavior Questionnaire: self and teacher reports). Secondary outcomes include depression, positive and negative affect, nature connectedness, and pro-environmental behaviors among children. We will explore, immediate benefits on teacher's well-being and positive and negative affect and sustained benefits among students at 3 months follow-up. For the primary outcome, we will explore moderators including child's sex, child's disability status, the green-space of neighbourhoods, the school's socio-economic position and teacher's experience. DISCUSSION: In conducting the first randomized controlled trial of the Open Sky School, our results could provide empirical evidence on the effectiveness of nature-based interventions in reducing mental health problems among elementary school children. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov: NCT05662436 on December 22, 2022.


Mental Health , Schools , Humans , Child , Students/psychology , Curriculum , Child Behavior , School Health Services , Randomized Controlled Trials as Topic
19.
Am J Prev Med ; 65(1): 83-91, 2023 07.
Article En | MEDLINE | ID: mdl-36849276

INTRODUCTION: Child sexual abuse remains a worldwide concern with devastating consequences on an individual's life. This longitudinal study investigates the associations between child sexual abuse (official reports versus retrospective self-reports) and subgroups by perpetrator identity (intrafamilial and extrafamilial), severity (penetration/attempted penetration, fondling/touching, noncontact), and chronicity (single, multiple episodes) and employment earnings in adulthood in a cohort followed for over 30 years. METHODS: The Quebec Longitudinal Study of Kindergarten Children database was linked to child protection services (official reports of sexual abuse) and to Canadian government tax returns (earned income). The sample included 3,020 individuals in Quebec French-language school kindergartens in 1986/1988, followed until 2017, and assessed with retrospective self-reports at age 22 years. Tobit regressions were used for associations with earnings (ages 33-37 years), adjusting for sex and family socioeconomic characteristics in 2021-2022. RESULTS: Individuals who experienced child sexual abuse had lower annual earnings. Those with retrospective self-reported sexual abuse (n=340) earned $4,031 (95% CI= -7,134, -931) less annually at ages 33-37 years than nonabused individuals (n=1,320), with pronounced differences for those with official reports (n=20), earning $16,042 (95% CI= -27,465, -4,618) less. Individuals self-reporting intrafamilial sexual abuse earned $4,696 (95% CI= -9,316, -75) less than those who experienced extrafamilial sexual abuse, whereas those self-reporting penetration/attempted penetration earned $6,188 (95% CI= -12,248, -129) less than those who experienced noncontact sexual abuse. CONCLUSIONS: Earnings gaps were highest for severest child sexual abuse (official reports, intrafamilial, penetrative). Future studies should investigate the underlying mechanisms. Improving support for victims of child sexual abuse could yield socioeconomic returns.


Child Abuse, Sexual , Child Abuse , Child , Humans , Young Adult , Adult , Longitudinal Studies , Cohort Studies , Retrospective Studies , Prospective Studies , Canada , Employment
20.
PLoS One ; 18(1): e0280203, 2023.
Article En | MEDLINE | ID: mdl-36634080

Prospective studies suggest that child maltreatment substantially increases the risk for depression in adulthood. However, the mechanisms underlying this association require further elucidation. In recent years, DNA methylation has emerged as a potential mechanism by which maltreatment experiences (a) could partly explain the emergence or aggravation of depressive symptoms (i.e., mediation) and/or (b) could increase (or decrease) the risk for depressive symptoms (i.e., moderation). The present study tested whether the methylation levels of nine candidate genes mediated and/or moderated the association between maltreatment experiences in childhood and depressive symptoms in emerging adulthood. The sample comprised 156 men aged between 18 and 35 years. Maltreatment experiences and depressive symptoms were assessed retrospectively using self-reported questionnaires. Methylation levels of nine candidate genes (COMT, FKBP5, IL6, IL10, MAOA, NR3C1, OXTR, SLC6A3 and SLC6A4), previously reported to be sensitive to early-life stress, were quantified from saliva samples. Maltreatment experiences in childhood were significantly associated with depressive symptoms in emerging adulthood. Both maltreatment experiences and depressive symptoms were associated with the methylation levels of two genomic sites, which cumulatively, but not individually, explained 16% of the association between maltreatment experiences in childhood and depressive symptoms in emerging adulthood. Moreover, maltreatment experiences in childhood interacted with the methylation levels of fourteen genomic sites, which cumulatively, but not individually, modulated the level of depressive symptoms in young male adults who were maltreated as children. However, none of these effects survived multiple testing correction. These findings bring attention to the cumulative effects of DNA methylation measured in several candidate genes on the risk of reporting depressive symptoms following maltreatment experiences in childhood. Nonetheless, future studies need to clarify the robustness of these putative cumulative effects in larger samples and longitudinal cohorts.


Child Abuse , Depression , Adult , Child , Humans , Male , Adolescent , Young Adult , Depression/genetics , DNA Methylation , Retrospective Studies , Prospective Studies , Serotonin Plasma Membrane Transport Proteins/genetics
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