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Abstract Background The oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder. Methods Female youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined. Results Youth with an eating disorder (n = 65, M age = 17.16 ± 3.5 years) were compared to healthy controls (HC; n = 65, M age = 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R; n = 43) or a bulimic spectrum eating disorder (ED-BP; n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33, p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38, p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554, p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60, p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30, p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63, p = 0.029). Conclusions These results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.

Abstract Purpose This study investigated the association between childhood eating behaviors and cortical morphology, in relation to sex and age, in a community sample. Methods Neuroimaging data of 71 children (mean age = 9.9 ± 1.4 years; 39 boys/32 girls) were obtained from the Nathan Kline Institute-Rockland Sample. Emotional overeating, food fussiness, and emotional undereating were assessed using the Children’s Eating Behavior Questionnaire. Cortical thickness was obtained at 81,924 vertices covering the entire cortex. Generalized Linear Mixed Models were used for statistical analysis. Results There was a significant effect of sex in the association between cortical thickness and emotional overeating (localized at the right postcentral and bilateral superior parietal gyri). Boys with more emotional overeating presented cortical thickening, whereas the opposite was observed in girls (p

Abstract Background The impact of the COVID-19 pandemic on young people with eating disorders (EDs) and their families was profound, with surging rates of hospitalizations and referrals reported internationally. This paper provides an account of the additional health and social costs of ED care for young people living in Canada incurred during the COVID-19 pandemic, drawing attention to the available data to inform these estimates while noting gaps in data capacities to account for a full view of the ED system of care. Methods Three methodologies were used to capture costs: (1) provincial administrative data holdings available at the Canadian Institute of Health Information (CIHI) were used by Deloitte Access Economics to conduct analyses on costs related to hospitalizations, emergency room visits, outpatient visits with physicians and loss of well-being from being on a waitlist. These were examined across three fiscal years (April 1 to March 31, 2019–2022) to compare costs from one year before to two years after the onset of the pandemic, (2) data collected on support-based community ED organizations and, (3) costs identified by young people, caregivers and health care professionals. Results Estimates of additional health care costs and social costs arising from ED care waitlists were estimated to have increased by 21% across the two years after the onset of the pandemic and is likely to represent an underestimate of costs. Costs related to some standard ED care services (e.g. day treatment programs) and support-based community ED organizations that saw a 118% increase in services during this time, are some examples of costs not captured in the current cost estimate. Conclusions This paper provides a first account of the additional health and social ED care costs associated with the pandemic, which indicate at minimum, a 21% increase. The results invite discussion for more investments in ED services for young people in Canada, as it is unclear if needs are expected to remain elevated. We suggest a call for a national surveillance strategy to improve data holdings to aid in managing services and informing policy. A robust strategy could open the door for much-needed, data-informed, system transformation efforts that can improve ED care for youth, families and clinicians.

Abstract Background The onset of the COVID-19 pandemic has had an adverse impact on children, youth, and families with eating disorders (EDs). The COVID-19 pandemic exacerbated pre-existing personal and financial costs to youth, caregivers, and health professionals accessing or delivering ED services. The objectives of this mixed methods study were to (1) understand the indirect, direct medical and non-medical costs reported by youth, caregivers, and clinicians; (2) understand how the COVID-19 pandemic may have impacted these costs, and (3) explore implications of these costs with regards to barriers and resources to inform future decisions for the ED system of care. Methods Youth (aged 16–25 years) with lived/living experience, primary caregivers, clinicians, and decision-makers were recruited with support from various partners across Canada to complete group specific surveys. A total of 117 participants responded to the survey. From those respondents, 21 individuals volunteered to further participate in either a discussion group or individual interview to provide additional insights on costs. Results Youth and primary caregivers reported costs relating to private services, transportation and impacts of not attending school or work. Additionally, primary caregivers reported the top direct medical cost being special food or nutritional supplements (82.8%). In discussion groups, youth and caregivers elaborated further on the challenges with long waitlists and cancelled services, impact on siblings and effect on family dynamics. Clinicians and decision-makers reported increased work expectations (64.3%) and fear/isolation due to COVID-19 in the workplace (58.9%). Through discussion groups, clinicians expanded further on the toll these expectations took on their personal life. Approximately 1 in 3 health professionals reported contemplating leaving their position in 1–2 years, with greater than 60% of this group stating this is directly related to working during the pandemic. Conclusions Findings demonstrate the need for increased support for youth and caregivers when accessing ED services both during crisis and non-crisis times. Additionally, attention must be given to acknowledging the experience of health professionals to support better retention and resource management as they continue to navigate challenges in the health care system.

Abstract Background Cross-sectional studies have shown that hyperactivity and impaired executive functioning are associated with symptoms of eating disorders in adolescence and adulthood. Whether hyperactivity and executive functions in early life can prospectively predict the emergence of eating disorder symptoms in adolescence remains unknown. The present study relies on a longitudinal design to investigate how hyperactivity at age 3, eating behaviours at age 3.5 and cognition at ages 3–6 were associated with the development of eating-disorder symptoms from 12 to 20 years old. Methods Using archival data collected since 1997 from the Quebec Longitudinal Study of Child Development cohort (N = 2, 223), we used Latent Curve Models to analyse predictors of youth’s trajectories of eating-disorder symptoms at four timepoints. Results A quadratic (curvilinear) trajectory of eating-disorder symptoms was found to be most representative of the data. Higher hyperactivity at age 3 was associated with higher levels of eating-disorder symptoms at age 12, and this association was partially mediated by higher levels of overeating and cognitive inflexibility in childhood. Cognitive inflexibility in childhood also mediated the association between hyperactivity at age 3 and increases in eating-disorder symptoms during adolescence. Furthermore, working memory was indirectly related to eating-disorder symptoms via the mediational role of cognitive flexibility. Conclusions Hyperactivity, overeating, cognitive inflexibility, and working memory early in life might precede the onset of eating-disorder symptoms in adolescence. Early behavioural and cognitive screening may help to identify children who are most at risk for eating disorders. This, in turn, could guide preventive interventions.

Abstract Background Given limited availability of informed treatments for people affected by eating disorders (EDs), there has been increasing interest in developing self-administered, technology-based ED interventions. However, many available interventions are limited to a specific ED diagnosis or assume that participants are ready to change. We developed a digital self-help application (called ASTrA) that was explicitly designed to be transdiagnostic and to help increase motivation for change. The aim of the present study was to describe the development and examine the psychometric properties, user satisfaction and rated potentials for practical use of our application. Methods The content of our application was based on concepts derived from self-determination theory, the transtheoretical model of change, and cognitive theory. The application was developed by a multidisciplinary team of clinicians, researchers, staff members and individuals with lived ED experience, each being involved in all steps of the application’s development. We tested validity, reliability, satisfaction and perceived feasibility for clinical implementation in an independent sample of 15 patients with an ED and 13 clinicians specialized in ED treatment. Psychometric properties were evaluated using descriptive statistics, correlations, content validity indices and intraclass coefficients. Differences in satisfaction ratings and perceived potential for clinical implementation of the application between clinicians and patients were examined using Mann–Whitney U tests. Results The digital application showed excellent validity (mean i-CVI: .93, range: .86–.96) and internal reliability (all Cronbach alpha’s > .88). Patients and clinicians both considered the application acceptable, appropriate, and feasible for use in clinical practice. Conclusions Findings suggest that our transdiagnostic interactive application has excellent psychometric properties. Furthermore, patients and clinicians alike were positive about the possible use of the application in clinical practice. The next step will be to investigate the application's effectiveness as an intervention to promote autonomous motivation and to facilitate remission in people on the waitlist for specialized ED treatment.

Abstract The COVID-19 pandemic has led to an unprecedented rise in rates and symptoms of eating disorders among Canadian youth. To date, there is a lack of national surveillance and costing data in Canada to inform policymakers and healthcare leaders on how to best address the surge in new and existing cases. This has resulted in the Canadian healthcare system being unprepared to adequately respond to the increased needs. Therefore, clinicians, researchers, policymakers, decision-makers, and community organizations across Canada are collaborating to compare pre-and post-pandemic costing data from national and province-level healthcare systems in an effort to address this gap. Results from this economic cost analysis will be an important first step in informing and guiding policy on possible adaptations to services to better fulfill the needs of youth with eating disorders in Canada. We highlight how gaps in surveillance and costing data can impact the field of eating disorders in an international context.

Abstract Background As a result of the public health measures put in place during the COVID-19 pandemic in Canada, many health services, including those for the treatment of eating disorders, were provided at a distance. This study aims to describe the adaptations made in specialized pediatric eating disorder programs in Canada and the impact of these adaptations on health professionals’ experience of providing care. Methods A mixed-methods design was used to survey healthcare professionals working in specialized pediatric eating disorder programs about adaptations to treatment made during the pandemic and the impact of these adaptations on their experience of providing care. Data were collected between October 2021 and March 2022 using a cross-sectional survey comprising 25 questions and via semi-structured interviews. Quantitative data were summarized using descriptive statistics and qualitative data were interpreted using qualitative content analysis. Results Eighteen healthcare professionals in Canada completed the online survey, of whom six also participated in the semi-structured interviews. The cross-sectional survey confirmed that, unlike in pre-pandemic times, the majority of participants provided medical care (15/18) and mental health care (17/18) at a distance during the pandemic, with most participants using telephone (17/18) and videoconferencing (17/18). Most (16/18) health professionals indicated that virtual care would continue to be used as a tool in pediatric ED treatment after the pandemic. Participants used a combination of virtual and in-person care, with most reporting weighing patients both in clinic (16/18) and virtually (15/18). Qualitative content analysis generated five themes: (1) responding to increased demand with insufficient resources; (2) adapting to changes in care due to the COVID-19 pandemic; (3) dealing with uncertainty and apprehension; (4) virtual care as an acceptable and useful clinical tool, and (5) optimal conditions and future expectations. Most interview participants (5/6) had globally positive views of virtual care. Conclusions Providing virtual multidisciplinary treatment for children and adolescents with eating disorders seemed feasible and acceptable to professionals during the pandemic. Moving forward, focusing on health professionals’ perspectives and providing appropriate training in virtual interventions is essential given their central role in successful implementation and continued use of virtual and hybrid care models.

Background Data on the outcomes of preterm newborns in South American countries are scarce. Given the great effect of low birth weight (LBW) and/or prematurity on children's neurodevelopment, it is extremely necessary to conduct studies on these phenomena in greater depth in more heterogeneous populations such as those ones from countries with limited resources. Methods We conducted a comprehensive literature search on databases including PubMed, the Cochrane Library, and Web of Science for articles published in Portuguese and English up to March 2021 involving children born and evaluated in Brazil. The analysis of the risk of bias was adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and used to evaluate the methodology of the included studies. Results From the eligible trials, 25 articles were selected for qualitative synthesis, and 5 of those, for quantitative synthesis (meta-analysis). The meta-analyses showed that children born with LBW presented lower scores on motor development when compared with controls (standardized mean difference: −1.15; 95% confidence interval [95%CI]: −1.56–−0.73]; I2: 80%) and also scored lower in terms of cognitive development (standardized mean difference: −0.71; 95% CI: −0.99–−0.44; I2: 67%). Conclusion The results of the present study reinforce that impaired motor and cognitive functions can be a significant long-term outcome of LBW. The lower the gestational age at delivery, the higher the risk of impairment in those domains. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database under number CRD42019112403.

Plain English summary The use of virtual care to treat adolescents and young adults with eating disorders has increased in recent years. To better understand what types of technologies are being used in virtual care and these technologies’ effectiveness, we systematically reviewed research studies that discussed the use of any technology to treat youth (which was defined as young people aged 25 years or under) with an eating disorder. We found 49 relevant studies. They revealed that videoconference therapy, mobile applications, and online self-help are most frequently used for virtual treatment. Of the 18 studies evaluating the effectiveness of these technologies, 15 found virtual care to be effective for reducing eating disorder symptoms. Studies describing patient experiences with these technologies, of which there were nine, suggested that patients overall were satisfied with receiving virtual care. Although these results are promising, research on virtual treatment is still lacking, especially on videoconferencing therapy and mobile applications.

Shifting motor actions from reflexively reacting to an environmental stimulus to predicting it allows for smooth synchronization of behavior with the outside world. This shift relies on the identification of patterns within the stimulus – knowing when a stimulus is predictable and when it is not – and launching motor actions accordingly. Failure to identify predictable stimuli results in movement delays whereas failure to recognize unpredictable stimuli results in early movements with incomplete information that can result in errors. Here we used a metronome task, combined with video-based eye-tracking, to quantify temporal predictive learning and performance to regularly paced visual targets at 5 different interstimulus intervals (ISIs). We compared these results to the random task where the timing of the target was randomized at each target step. We completed these tasks in female pediatric psychiatry patients (age range: 11–18 years) with borderline personality disorder (BPD) symptoms, with (n = 22) and without (n = 23) a comorbid attention-deficit hyperactivity disorder (ADHD) diagnosis, against controls (n = 35). Compared to controls, BPD and ADHD/BPD cohorts showed no differences in their predictive saccade performance to metronome targets, however, when targets were random ADHD/BPD participants made significantly more anticipatory saccades (i.e., guesses of target arrival). The ADHD/BPD group also significantly increased their blink rate and pupil size when initiating movements to predictable versus unpredictable targets, likely a reflection of increased neural effort for motor synchronization. BPD and ADHD/BPD groups showed increased sympathetic tone evidenced by larger pupil sizes than controls. Together, these results support normal temporal motor prediction in BPD with and without ADHD, reduced response inhibition in BPD with comorbid ADHD, and increased pupil sizes in BPD patients. Further these results emphasize the importance of controlling for comorbid ADHD when querying BPD pathology.

Introduction In recent years, eye-tracking has been proposed as a promising tool to identify potential biomarkers for mental disorders, including major depression. We will conduct an updated systematic review and meta-analysis on eye-tracking research in adults with major depressive disorder or other clinically diagnosed depressive disorders.Methods and analysis This protocol follows all reporting items in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol extension. We will conduct a systematic search of PubMed, PsycINFO, Google Scholar and EMBASE for sources published up until March 2023. Abstract and full-text review will be completed independently by two reviewers. Non-randomised studies using eye movement tasks in individuals with a depressive disorder versus controls will be included. Eye movement tasks of interest include, but are not limited to, saccade, smooth pursuit, fixation, free-viewing, attentional disengagement, visual search and attentional blink tasks. Results will be categorised by eye movement task. Risk of bias will be assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and confidence in cumulative evidence will be assessed using Grading of Recommendations, Assessment, Development and Evaluation criteria.Ethics and dissemination Ethics approval is not required due to the nature of the proposed analysis. Results will be disseminated through a journal article, conference presentations and/or dissertations.

Abstract Introduction Eating disorders (EDs) have long been considered conditions exclusively affecting women, and studies in the ED field regularly exclude men. Research efforts are needed to better understand the role of gender and sex in EDs. This review describes the role of gender and sex in the development of EDs from a biopsychosocial perspective. Methods The primary hypothesis of this narrative review is that gender and sex interact to influence ED risk. The literature review was conducted using the PubMed database. Results This review first presents the general characteristics and prevalence of EDs according to gender and sex. Next, neurodevelopmental processes, neurobiology, gender roles, body image, and the minority stress model are addressed. Lastly, research perspectives to better include gender and sex in the field of EDs are discussed (e.g., representation of gender and sex diversities, development of appropriate assessment tools, and increasing awareness). Conclusion Although substantial knowledge gaps remain, there is a growing recognition of the importance of integrating gender and sex in ED research that holds promise for further development in the field.

Plain English summary Eating disorders, typically involving preoccupation with eating, excessive exercise, and body image issues, are particularly common in adolescence. However, their evolution over time remains unclear as certain signs and symptoms may appear sooner than others. The current study studied the development of eating disorder symptoms in a community cohort followed from birth to adulthood. This study describes trajectories of eating disorder symptoms and risk from age 12 to 20 in both boys and girls. Results showed that the largest increase in eating disorder symptoms occurs between 12 and 15 years of age, both in overall symptomatology as well as in specific symptoms such as loss-of-control when eating, feeling overweight, and attributing importance to food. Additionally, more girls than boys appeared at risk for eating disorders, although the patterns represented by the trajectories were similar in both sexes. Our results highlight the importance of starting early prevention programs before the beginning of adolescence, when symptoms usually start to manifest.

Objective: To validate the Family Health Behavior Scale (FHBS) for Brazilian families. Methods: The sample included 272 children aged 5 to 12 years old. Caregivers and their healthy answered the FHBS and questions about physical activity. In addition, anthropometric measurements of the children's weight and height were performed, as well as the bioimpedance exam. The scale was translated and the following validities were assessed: content (qualitative analysis and content validity index), construct (factor analysis) and concurrent validity (difference between domains and the total score with the categories of BMI, fat percentage and physical activity). Reliability (Cronbach's alpha, ceiling-floor effect, two-half test, intraclass correlation and Bland – Altman) was also assessed. Results: FHBS instrument performed well with regard to the psychometric properties in the Brazilian population. The content validity index was 0.987. Fit indices of the factor analysis were considered satisfactory, according to Bartlett's sphericity test (χ 2 = 1927, df = 351; p < 0.001) and the Kaiser-Meyer-Olkin index (KMO = 0.789). Concurrent validity, the differences between the mean of the domains and the total score between the categories of BMI (p = 0.011), percentage of fat (0.004) and physical activity (p < 0.001) were all significant. The reliability results were Cronbach's alpha internal consistency = 0.83, adequate ceiling-floor effect, 0.8105 (0.09 SD) two-half test, 0.626 intraclass correlation (95% CI: 0.406 to 0.777) and Bland – Altman -0.840 (-22.76 to 21.07). Conclusion: The FHBS adapted for the Brazilian population showed evidence of adequate psychometric performance.

Abstract Objectives Accurate and complete study reporting allows evidence users to critically appraise studies, evaluate possible bias, and assess generalizability and applicability. We evaluated the extent to which recent studies on depression screening accuracy were reported consistent with Standards for Reporting of Diagnostic Accuracy Studies (STARD) statement requirements. Methods MEDLINE was searched from January 1, 2018 through May 21, 2021 for depression screening accuracy studies. Results 106 studies were included. Of 34 STARD items or sub‐items, the number of adequately reported items per study ranged from 7 to 18 (mean = 11.5, standard deviation [SD] = 2.5; median = 11.5), and the number inadequately reported ranged from 3 to 17 (mean = 10.1, SD = 2.5; median = 10.0). There were eight items adequately reported, seven partially reported, 11 inadequately reported, and four not applicable in ≥50% of studies; the remaining four items had mixed reporting. Items inadequately reported in ≥70% of studies related to the rationale for index test cut‐offs examined, missing data management, analyses of variability in accuracy results, sample size determination, participant flow, study registration, and study protocol. Conclusion Recently published depression screening accuracy studies are not optimally reported. Journals should endorse and implement STARD adherence.

Predictive modeling studies have started to reveal brain measures underlying cognition; however, most studies are based on cross-sectional data (brain measures acquired at one time point). Since brain development comprises of continuously ongoing events leading to cognitive development, predictive modeling studies need to consider ‘longitudinal brain change’ as opposed to ‘cross-sectional brain measures’. Using longitudinal neuroimaging and cognitive data (global executive composite score, an index of executive function) from 82 individuals (aged 5–14 years, scanned 3 times), we built highly accurate prediction models (r = 0.61, p = 1.6e-09) of future cognition (assessed at visit 3) based on developmental changes in cortical anatomy (from visit 1 to 2). More importantly, longitudinal brain change (i.e. change in cortical anatomy from visit 1 to 2) and cross-sectional brain measures (cortical anatomy at visit 1 and 2) were critical for predicting future cognition, suggesting the need for considering longitudinal brain change in predicting cognitive outcomes.

BackgroundThe incidence of eating disorders (EDs) among adolescents has significantly increased since the beginning of the COVID-19 pandemic. Hybrid care, which combines web-based and in-person modalities, is a promising approach for adolescents with EDs but remains understudied in this population. ObjectiveWe aimed to implement a novel hybrid (web-based and in-person) intensive ambulatory care program for youth and evaluate its feasibility, acceptability, and preliminary effectiveness. MethodsWe will use a naturalistic pretest-posttest design to evaluate our proposed pilot Intensive Ambulatory Care Program (IACP). This novel type of day hospital care follows evidence-based principles and uses a family-centered, educational, and motivational approach. It will be tailored to the psychological needs of each participant and will be delivered in a hybrid format. A total of 100 participants meeting the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) criteria for EDs, aged 12-18 years, will be recruited over the 2-year trial period. We will examine recruitment, retention, and adhesion-to-protocol rates; participant and family satisfaction; and preliminary effectiveness using quantitative self-report questionnaires. ResultsRolling recruitment will take place from winter 2022 to fall 2023, during which time we expect to recruit approximately 80% (100/120) of eligible participants, retain at least 75% (75/100) of enrolled participants and have at least 70% (70/100) of enrolled participants complete at least one therapeutic session per week and all pre- and postintervention questionnaires. Data collection will occur concurrently. We base our recruitment and retention estimates on previous literature and consider that the highly flexible design of the IACP and the fact that no extra work will be required of individuals in the program to participate in the study, will lead to high levels of feasibility. We anticipate that participants and their families will be satisfied with both the program and hybrid delivery format. We expect that participation in the IACP will be associated with a medium effect size reduction in ED psychopathology from baseline to end of treatment. The data analysis and manuscript writing are expected to be completed by the summer of 2024. ConclusionsGiven the high clinical burden associated with EDs, this study has the potential to fill an important research gap by testing the implementation of a novel hybrid mode of intervention. If feasible, acceptable, and effective, the IACP could lead to important improvements in health care services for adolescents with EDs. International Registered Report Identifier (IRRID)PRR1-10.2196/37420

Genetic and early environmental factors are interwoven in the etiology of Borderline Personality Disorder (BPD). Epigenetic mechanisms offer the molecular machinery to adapt to environmental conditions. There are gaps in the knowledge about how epigenetic mechanisms are involved in the effects of early affective environment, development of BPD, and psychotherapy response. We reviewed the available evidence of the effects of psychotherapy on changes in DNA methylation and conducted a pilot study in a sample of 11 female adolescents diagnosed with BPD, exploring for changes in peripheral DNA methylation of FKBP5 gene, which encodes for a stress response protein, in relation to psychotherapy, on symptomatology and underlying psychological processes. For this purpose, measures of early trauma, borderline and depressive symptoms, psychotherapy outcome, mentalization, and emotional regulation were studied. A reduction in the average FKBP5 methylation levels was observed over time. Additionally, the decrease in FKBP5 methylation observed occurred only in those individuals who had early trauma and responded to psychotherapy. The results suggest an effect of psychotherapy on epigenetic mechanisms associated with the stress response. The finding that epigenetic changes were only observed in patients with early trauma suggests a specific molecular mechanism of recovery. The results should be taken with caution given the small sample size. Also, further research is needed to adjust for confounding factors and include endocrinological markers and therapeutic process variables.

Abstract Objectives Depression screening tool accuracy studies should be conducted with large enough sample sizes to generate precise accuracy estimates. We assessed the proportion of recently published depression screening tool diagnostic accuracy studies that reported sample size calculations; the proportion that provided confidence intervals (CIs); and precision, based on the width and lower bounds of 95% CIs for sensitivity and specificity. In addition, we assessed whether these results have improved since a previous review of studies published in 2013–2015. Methods MEDLINE was searched from January 1, 2018, through May 21, 2021. Results Twelve of 106 primary studies (11%) described a viable sample size calculation, which represented an improvement of 8% since the last review. Thirty‐six studies (34%) provided reasonably accurate CIs. Of 103 studies where 95% CIs were provided or could be calculated, seven (7%) had sensitivity CI widths of ≤10%, whereas 58 (56%) had widths of ≥21%. Eighty‐four studies (82%) had lower bounds of CIs

Objective: To assess the level of agreement in health‐related quality of life between children with Post‐infectious Bronchiolitis Obliterans and their parent (so‐called proxy). Methods: Participants aged between 8and 17 years who had been previously diagnosed with Post‐infectious Bronchiolitis Obliterans were regularly followed up at a pediatric pulmonology outpatient clinic. Parents or legal guardians (caregivers) of these patients were also recruited for the study. A validated and age‐appropriate version of the Pediatric Quality of Life Inventory 4.0 was used for the assessment of health‐related quality of life. Caregivers completed the corresponding proxy versions of the questionnaire. The correlation between self and proxy reports of health‐related quality of life was determined by intra‐class correlation coefficient and dependent t‐tests. Results: The majority of participants were males (79.4%), and the average age was 11.8 years. Intra‐class correlations between each of the Pediatric Quality of Life Inventory 4.0 domains and the total score were all lower than 0.6, with a range between 0.267 (poor) and 0.530 (fair). When the means of each domain and the total score of the questionnaires were compared, caregivers were observed to have a significantly lower health‐related quality of life score than children, with the exception of the social domain in which the difference was not significant. However, the differences in score exceeded the critical threshold difference of four points in all other domains. Conclusion: Proxies of children and adolescents with Post‐infectious Bronchiolitis Obliterans appear to consistently perceive their children as having lower health‐related quality of life than how the patients perceive themselves. Resumo: Objetivo: Avaliar o nível de concordância a respeito da qualidade de vida relacionada à saúde entre crianças com bronquiolite obliterante pós‐infecciosa e seus pais (responsáveis). Métodos: Os participantes entre 8‐17 anos, anteriormente diagnosticados com bronquiolite obliterante pós-infecciosa, foram acompanhados regularmente no ambulatório de pneumologia pediátrica. Os pais ou responsáveis legais (cuidadores) desses pacientes também foram convidados a participar do estudo. Uma versão validada e adequada para a idade do Inventário Pediátrico de Qualidade de Vida, versão 4.0, foi utilizada para a avaliação da qualidade de vida relacionada à saúde. Os cuidadores concluíram as versões do questionário correspondentes aos responsáveis. A correlação entre os autorrelatos e os relatos dos responsáveis da qualidade de vida relacionada à saúde foi determinada pelo coeficiente de correlação intraclasse e pelos testes t dependentes. Resultados: A maior parte dos participantes era do sexo masculino (79,4%) e a idade média foi 11,8 anos. As correlações intraclasse entre cada um dos domínios do Inventário Pediátrico de Qualidade de Vida e o escore total foram todas inferiores a 0,6, com intervalo entre 0,267 (baixo) e 0,530 (justo). Quando as médias de cada domínio e o escore total dos questionários foram comparados, observamos que os cuidadores apresentaram qualidade de vida relacionada à saúde significativamente menor em comparação com as crianças, com exceção do domínio social, no qual a diferença não foi significativa. Contudo, as diferenças no escore ultrapassaram o limite de diferença essencial de 4 pontos em todos os outros domínios. Conclusão: Os responsáveis pelas crianças e adolescentes com bronquiolite obliterante pós-infecciosa parecem perceber de forma consistente que suas crianças possuem qualidade de vida relacionada à saúde menor que os próprios pacientes. Keywords: Health‐related quality of life, Bronchiolitis obliterans, Children, Palavras‐chave: Qualidade de vida relacionada à saúde, Bronquiolite obliterante, Crianças

Objective: To validate the Brazilian Portuguese version of the Family Environment Assessment questionnaire (Inventaire du Milieu Familial). Methods: The validation process was carried out in two stages. First, translation and back‐translation were performed, and in the second phase, the questionnaire was applied in 72 families of children between 0 and 24 months for the validation process. The tool consists of the following domains: mother's communication ability; behavior; organization of the physical and temporal environment; collection/quantity of toys; maternal attitude of constant attention toward her baby; diversification of stimuli; baby's behavior. The following was performed for the scale validation: 1 – content analysis (judgment); 2 – construct analysis (factorial analysis – Kaiser‐Meyer‐Olkin, Bartlett, and Pearson's correlation tests); 3 – criterion analysis (calculation of Cronbach's alpha coefficient, intraclass correlations, and split‐half correlations). Results: The mean age of the children was 9 ± 6.7 months, and of these, 35 (48.6%) were males. Most correlations between items and domains were significant. In the factorial analysis of the scale, Kaiser‐Meyer‐Olkin values were 0.76, Bartlett's test showed a p‐value

Introduction Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk.Methods and analysis This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study.Ethics and dissemination The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l’Estrie–CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation.Trial registration number ChiCTR1800017773.Protocol version November 11, 2020 (Version #5).

Background: Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with adverse neurodevelopmental outcomes in children, but evidence remains mixed regarding sex differences in this association. Objective: To examine the prospective association between prenatal PBDE exposure and cognitive ability in young children, as well as potential sex differences. Methods: The study was conducted in a multi-site Canadian pregnancy cohort recruited in 2008–11. PBDEs were measured in maternal plasma samples collected early in pregnancy. Cognitive ability was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) in children at age 3 years (mean = 3.4). Multiple linear regression was used to analyze the association between maternal PBDE plasma concentrations (lipid-standardized and log10-transformed) and Verbal, Performance, and Full Scale IQ scores on the whole sample and stratified by sex, adjusting for confounders. Results: The sample was composed of 592 children (291 boys and 301 girls). A tenfold increase in maternal blood PBDE concentration (sum of BDE-47, −99, −100, and −153) was associated with lower Full Scale scores in boys (−3.4 points; 95% CI: −7.0, 0.1), after adjusting for confounders. BDE-47 was the congener with the highest concentrations in maternal blood and a tenfold increase in exposure was associated with significantly lower Full Scale IQ scores in boys (−4.4 points; 95% CI: −7.9, −0.9), after adjusting for confounders. Verbal and Performance IQ scores were similarly associated with PBDE exposure. Maternal blood PBDE concentrations were not associated with IQ scores in girls. Conclusions: Prenatal exposure to background levels of PBDEs, especially BDE-47, was associated with lower IQ scores in boys, but not in girls. Our results support that exposure to PBDEs during early development may be sex-dependent and detrimental to a child’s neurodevelopmental trajectory.

Abstract Background This scoping review addressed the question ‘what do we know about stress-related changes in saliva and dental caries in general population?’ Methods The review was conducted using electronic searches via Embase, MEDLINE, PsycINFO, CINAHL and WoS. All published human studies with both observational and experimental designs were included. Two reviewers independently reviewed eligible articles and extracted the data. The studies’ quality was assessed using the Effective Public Health Practice Project Quality Assessment Tool. Results Our search identified 232 reports, of which six were included in this review. All six studies were conducted in children and used salivary cortisol as stress marker. The studies varied by design, types of stressors, children’s caries experience, methods of saliva collection. Four studies reported a positive association between saliva cortisol levels and caries (p 0.05). The quality of the included studies was weak to moderate. Conclusions There is lack of evidence about an association between stress-related changes in saliva and caries. Well-designed longitudinal studies with rigorous measurement technics for stress, saliva and dental caries are necessary. This will help to generate new insights into the multifactorial etiology of caries and provide evidence for a rational method for its control.

Abstract Background Some authors have hypothesized that Treatment-Resistant Unipolar Depression (TRD-UP) should be considered within the bipolar spectrum disorders and that hidden bipolarity may be a risk factor for TRD-UP. However, there are neither studies comparing clinical and sociodemographic data of patients with TRD-UP versus Bipolar (BP) disorders nor are there any examining differences versus Bipolar type I (BP-I) and Bipolar type II (BP-II). Methods Charts analysis was conducted on 194 patients followed at the Mood Disorders Clinic of the McGill University Health Center. Sociodemographic, clinical features and depression scales were collected from patients meeting DSM-IV criteria for TRD-UP (n = 100) and BP (n = 94). Binary logistic regression analysis was conducted to examine clinical predictors independently associated with the two disorders. Results Compared to BP, TRD-UP patients exhibited greater severity of depression, prevalence of anxiety and panic disorders, melancholic features, Cluster-C personality disorders, later onset of depression and fewer hospitalizations. Binary logistic regression indicated that higher comorbidity with anxiety disorders, higher depression scale scores and lower global assessment of functioning (GAF) scores, and lower number of hospitalizations and psychotherapies differentiated TRD-UP from BP patients. We also found that the rate of unemployment and the number of hospitalizations for depression was higher in BP-I than in BP-II, while the rate of suicide attempts was lower in BP-I than in BP-II depressed patients. Conclusions These results suggest that TRD-UP constitutes a distinct psychopathological condition and not necessarily a prodromal state of BP depression.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

Numerous studies have shown differences in the functioning in the areas of the frontal-limbic circuitry between depressed patients and controls. However, current knowledge on frontal-limbic neural substrates of individual differences in mood states in everyday life in healthy individuals is scarce. The present study investigates anatomical, resting-state, and functional neural correlates of daily mood states in healthy individuals. We expected to observe associations between mood and the frontal-limbic circuitry and the default-mode network (DMN). A total of 42 healthy adults (19 men, 23 women; 34 ± 1.2 years) regularly followed for behavior and psychosocial functioning since age of 6, underwent a functional magnetic resonance imaging scan, and completed a daily diary of mood states and related cognitions for 5 consecutive days. Results showed that individuals with smaller left hippocampal gray matter volumes experienced more negative mood and rumination in their daily life. Greater resting-state functional connectivity (rsFC) within the DMN, namely between posterior cingulate cortex (PCC) and medial prefrontal cortex regions as well as between PCC and precuneus, was associated with both greater negative and positive mood states in daily life. These rsFC results could be indicative of the role of the DMN regional functioning in emotional arousal, irrespective of valence. Lastly, greater daily positive mood was associated with greater activation in response to negative emotional stimuli in the precentral gyri, previously linked to emotional interference on cognitive control. Altogether, present findings might reflect neural mechanisms underlying daily affect and cognition among healthy individuals.

BACKGROUND:Difficult temperament in infancy is a risk factor for forms of later internalizing and externalizing psychopathology, including depression and anxiety. A better understanding of the roots of difficult temperament requires assessment of its early development with a genetically informative design. The goal of this study was to estimate genetic and environmental contributions to individual differences in infant negative emotionality, their persistence over time and their influences on stability between 5 and 18 months of age. METHOD:Participants were 244 monozygotic and 394 dizygotic twin pairs (49.7% male) recruited from birth. Mothers rated their twins for negative emotionality at 5 and 18 months. Longitudinal analysis of stability and innovation between the two time points was performed in Mplus. RESULTS:There were substantial and similar heritability (approximately 31%) and shared environmental (57.3%) contributions to negative emotionality at both 5 and 18 months. The trait's interindividual stability across time was both genetically- and environmentally- mediated. Evidence of innovative effects (i.e., variance at 18 months independent from variance at 5 months) indicated that negative emotionality is developmentally dynamic and affected by persistent and new genetic and environmental factors at 18 months. CONCLUSIONS:In the first two years of life, ongoing genetic and environmental influences support temperamental negative emotionality but new genetic and environmental factors also indicate dynamic change of those factors across time. A better understanding of the source and timing of factors on temperament in early development, and role of sex, could improve efforts to prevent related psychopathology.

Serotonin plays an important role in the etiology of depression. Serotonin is also crucial for brain development. For instance, animal studies have demonstrated that early disruptions in the serotonin system affect brain development and emotion regulation in later life. A plausible explanation is that environmental stressors reprogram the serotonin system through epigenetic processes by altering serotonin system gene expression. This in turn may affect brain development, including the hippocampus, a region with dense serotonergic innervations and important in stress-regulation. The aim of this study was to test whether greater DNA methylation in specific CpG sites at the serotonin transporter promoter in peripheral cells is associated with childhood trauma, depression, and smaller hippocampal volume. We were particularly interested in those CpG sites whose state of methylation in peripheral cells had previously been associated with in vivo measures of brain serotonin synthesis. Thirty-three adults with Major Depressive Disorder (MDD) (23 females) and 36 matched healthy controls (21 females) were included in the study. Depressive symptoms, childhood trauma, and high-resolution structural MRI for hippocampal volume were assessed. Site-specific serotonin transporter methylation was assessed using pyrosequencing. Childhood trauma, being male, and smaller hippocampal volume were independently associated with greater peripheral serotonin transporter methylation. Greater serotonin transporter methylation in the depressed group was observed only in SSRI-treated patients. These results suggest that serotonin transporter methylation may be involved in physiological gene-environment interaction in the development of stress-related brain alterations. The results provide some indications that site-specific serotonin transporter methylation may be a biomarker for serotonin-associated stress-related psychopathology.

BackgroundCognitive reactivity to sad mood is a vulnerability marker of depression. Implicit self-depressed associations are related to depression status and reduced remission probability. It is unknown whether these cognitive vulnerabilities precede the first onset of depression.AimTo test the predictive value of cognitive reactivity and implicit self-depressed associations for the incidence of depressive disorders.MethodsProspective cohort study of 834 never-depressed individuals, followed over a two-year period. The predictive value of cognitive reactivity and implicit self-depressed associations for the onset of depressive disorders was assessed using binomial logistic regression. The multivariate model corrected for baseline levels of subclinical depressive symptoms, neuroticism, for the presence of a history of anxiety disorders, for family history of depressive or anxiety disorders, and for the incidence of negative life events.ResultsAs single predictors, both cognitive reactivity and implicit self-depressed associations were significantly associated with depression incidence. In the multivariate model, cognitive reactivity was significantly associated with depression incidence, together with baseline depressive symptoms and the number of negative life events, whereas implicit self-depressed associations were not.ConclusionCognitive reactivity to sad mood is associated with the incidence of depressive disorders, also when various other depression-related variables are controlled for. Implicit self-depressed associations predicted depression incidence in a bivariate test, but not when controlling for other predictors.

Catechol-O-methyltransferase (COMT) plays an essential role in degradation of extracellular dopamine in prefrontal regions of the brain. Although a polymorphism in this gene, COMT Val(158)Met, affects human behavior in response to stress little is known about its effect on dopaminergic activity associated with the human stress response, which may be of interest for stress-related psychiatric disorders such as psychosis. We aimed to investigate the effect of variations in COMT genotype on in vivo measures of stress-induced prefrontal cortex (PFC) dopaminergic processing and subjective stress responses. A combined sample of healthy controls and healthy first-degree relatives of psychosis patients (n = 26) were subjected to an [(18)F]fallypride Positron Emission Tomography scan. Psychosocial stress during the scan was induced using the Montreal Imaging Stress Task and subjective stress was assessed every 12 minutes. Parametric t-maps, generated using the linear extension of the simplified reference region model, revealed an effect of COMT genotype on the spatial extent of [(18)F]fallypride displacement. Detected effects of exposure to psychosocial stress were unilateral and remained restricted to the left superior and right inferior frontal gyrus, with Met-hetero- and homozygotes showing less [(18)F]fallypride displacement than Val-homozygotes. Additionally, Met-hetero- and homozygotes experienced larger subjective stress responses than Val-homozygotes. The direction of the effects remained the same when the data was analyzed separately for controls and first-degree relatives. The human stress response may be mediated in part by COMT-dependent dopaminergic PFC activity, providing speculation for the neurobiology underlying COMT-dependent differences in human behaviour following stress. Implications of these results for stress-related psychopathology and models of dopaminergic functioning are discussed.

The main challenge in addressing the role of DNA methylation in human behaviour is the fact that the brain is inaccessible to epigenetic analysis in living humans. Using positron emission tomography (PET) measures of brain serotonin (5-HT) synthesis, we found in a longitudinal sample that adult males with high childhood-limited aggression (C-LHPA) had lower in vivo 5-HT synthesis in the orbitofrontal cortex (OBFC). Here we hypothesized that 5-HT alterations associated with childhood aggression were linked to differential DNA methylation of critical genes in the 5-HT pathway and these changes were also detectable in peripheral white blood cells. Using pyrosequencing, we determined the state of DNA methylation of SLC6A4 promoter in T cells and monocytes isolated from blood of cohort members (N = 25) who underwent a PET scan, and we examined whether methylation status in the blood is associated with in vivo brain 5-HT synthesis. Higher levels of methylation were observed in both T cells and monocytes at specific CpG sites in the C-LHPA group. DNA methylation of SLC6A4 in monocytes appears to be associated more reliably with group membership than T cells. In both cell types the methylation state of these CpGs was associated with lower in vivo measures of brain 5-HT synthesis in the left and right lateral OBFC (N = 20) where lower 5-HT synthesis in C-LHPA group was observed. Furthermore, in vitro methylation of the SLC6A4 promoter in a luciferase reporter construct suppresses its transcriptional activity supporting a functional role of DNA methylation in SLC6A4 promoter regulation. These findings indicate that state of SLC6A4 promoter methylation is altered in peripheral white blood cells of individuals with physical aggression during childhood. This supports the relevance of peripheral DNA methylation for brain function and suggests that peripheral SLC6A4 DNA methylation could be a marker of central 5-HT function.

Objective. Irritable and nonirritable depressed patients differ on demographic and clinical characteristics. We investigated whether this extends to psychological and physiological measures. Method. We compared irritable and nonirritable unipolar depressed patients on symptomatology, personality, and (psycho)physiological measures (cortisol, cholesterol, and heart rate variability). Symptomatology was reassessed after one year, and we also compared depressed patients who were irritable or non-irritable at both time points (Irr++ versus Irr−−). Results. Almost half (46%; N=420) of the sample was classified as irritable. These patients scored higher on depression severity, anxiety, hypomanic symptoms, and psychological variables. No differences were observed on physiological markers after correction for depression severity. The same pattern was found when comparing Irr++ and Irr−− groups. Conclusion. Irritable and non-irritable depressed patients differ on clinical and psychological variables, but not on the currently investigated physiological markers. The clinical relevance of the distinction and the significance of the hypomanic symptoms remain to be demonstrated.

Adults exhibiting severe impulsive and aggressive behaviors have multiple indices of low serotonin (5-HT) neurotransmission. It remains unclear though whether low 5-HT mediates the behavior or instead reflects a pre-existing vulnerability trait.In the present study, positron emission tomography with the tracer alpha-[(11)C]methyl-L-tryptophan ((11)C-AMT) was used to compare 5-HT synthesis capacity in two groups of adult males from a 21-year longitudinal study (mean age +/- SD: 27.1+/-0.7): individuals with a history of childhood-limited high physical aggression (C-LHPA; N = 8) and individuals with normal (low) patterns of physical aggression (LPA; N = 18). The C-LHPA males had significantly lower trapping of (11)C-AMT bilaterally in the orbitofrontal cortex and self-reported more impulsiveness. Despite this, in adulthood there were no group differences in plasma tryptophan levels, genotyping, aggression, emotional intelligence, working memory, computerized measures of impulsivity, psychosocial functioning/adjustment, and personal and family history of mood and substance abuse disorders.These results force a re-examination of the low 5-HT hypothesis as central in the biology of violence. They suggest that low 5-HT does not mediate current behavior and should be considered a vulnerability factor for impulsive-aggressive behavior that may or may not be expressed depending on other biological factors, experience, and environmental support during development.