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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 FROM AUTHOR]

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 FROM AUTHOR]

Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion. We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED. Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups (Q < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3, CSGALNACT1, NEGR1, NR1H3) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation. Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology. [ABSTRACT FROM AUTHOR]

Background: Prenatal maternal stress is increasingly recognized as a risk factor for offspring mental health challenges. DNA methylation may be a mechanism, but few studies directly tested mediation. These few integrative studies are reviewed along with studies from three research areas: prenatal maternal stress and child mental health, prenatal maternal stress and child DNA methylation, and child mental health and DNA methylation.Methods: We conducted a narrative review of articles in each research area and the few published integrative studies to evaluate the state of knowledge.Results: Prenatal maternal stress was related to greater offspring internalizing and externalizing symptoms and to greater offspring peripheral DNA methylation of the NR3C1 gene. Youth mental health problems were also related to NR3C1 hypermethylation while epigenome-wide studies identified genes involved in nervous system development. Integrative studies focused on infant outcomes and did not detect significant mediation by DNA methylation though methodological considerations may partially explain these null results.Limitations: Operationalization of prenatal maternal stress and child mental health varied greatly. The few published integrative studies did not report conclusive evidence of mediation by DNA methylation.Conclusions: DNA methylation likely mediates the association between prenatal maternal stress and child mental health. This conclusion still needs to be tested in a larger number of integrative studies. Key empirical and statistical considerations for future research are discussed. Understanding the consequences of prenatal maternal stress and its pathways of influence will help prevention and intervention efforts and ultimately promote well-being for both mothers and children. [ABSTRACT FROM AUTHOR]

Although treatment dropout is common among patients with eating disorders, very few studies have examined predictors of non‐completion in day treatment. We investigated various potential predictors of dropout from adult day treatment. Participants were 295 adult patients with a diagnosis of Anorexia Nervosa (restricting or binge‐eating/purging subtype), Bulimia Nervosa (BN), Other Specified Feeding or Eating Disorder, or Avoidant Restrictive Food Intake Disorder. Predictors included eating‐disorder characteristics, motivation at the commencement of treatment, Body Mass Index (BMI), time spent in treatment and personality dimensions. Logistic regression analyses showed that for patients with a BMI of less than 20 at the start of treatment, low BMI was a significant predictor of staff‐initiated termination due to not meeting weight gain goals. Furthermore, completing less than 6 weeks of treatment was associated with staff‐initiated termination. For the whole sample, those with higher changes in weight over the course of treatment were less likely to terminate prematurely. None of the other predictor variables yielded significant results. Results of the current study highlight characteristics of patients who are more likely not to complete day treatment and can help identify patients who may be at risk for not succeeding in multi‐diagnostic day treatment programs. Highlights: For patients attending day treatment, low BMI at the start of treatment was a significant predictor of staff‐initiated discharge in participants who entered the program with a BMI < 20For all patients, larger changes in BMI over the course of treatment predicted higher likelihood of completing treatmentResults can help identify which patients may be at risk for not succeeding in multi‐diagnostic day treatment programs and address this risk in the transition to a higher level of care from lower levels [ABSTRACT FROM AUTHOR]

Objective: Findings show virtual therapy (conducted using internet‐based videoconferencing techniques) to be a viable alternative to in‐person therapy for a variety of mental‐health problems. COVID‐19 social‐distancing imperatives required us to substitute virtual interventions for in‐person sessions routinely offered in our outpatient eating disorder (ED) program—and afforded us an opportunity to compare the two treatment formats for clinical efficacy. Methods: Using self‐report assessments, we compared outcomes in a historical sample of 49 adults with heterogeneous EDs (treated in‐person over 10–14 weeks in individual and group therapies) to those of 76 patients receiving comparable virtual treatments, at distance, during the COVID‐19 outbreak. Linear mixed models were used to study symptom changes over time and to test for differential effects of treatment modality. Results: Participants in both groups showed similar improvements on eating symptoms, levels of weight gain (in individuals in whom gain was indicated), and satisfaction with services. Discussion: Our results suggest that short‐term clinical outcomes with virtual and in‐person ED therapies are comparable, and point to potentials of virtual therapy for situations in which geographical distance or other barriers impede physical access to trained therapists or specialized treatments. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Objective: Identifying modifiable predictors of outcomes following treatment for eating disorders may help to tailor interventions to patients' individual needs, improve treatment efficacy, and develop new interventions. The goal of this meta‐analysis was to quantify the association between pretreatment motivation and posttreatment changes in eating disorder symptomology. Method: We reviewed 196 longitudinal studies reporting on change on indices of overall eating‐disorder symptomatology, weight gain, binge‐eating, vomiting, anxiety/depression, and treatment adherence. Meta‐analyses were performed using two complementary approaches: (a) combined probability analysis using the added Z's method; (b) effect size analyses. Using random‐effect models, effect sizes were pooled when there were at least three studies with the same type of statistical design and reporting statistics on the same outcome. Heterogeneity in study outcome was evaluated using Q and I2 statistics. Studies were reviewed qualitatively when the number of studies or reported data were insufficient to perform a meta‐analysis. Results: Forty‐two articles were included. Although samples and treatments differed substantially across studies, results across studies were remarkably consistent. Both combined‐probability and effect‐size analyses indicated positive effects of pretreatment motivation on improvement in general eating‐disorder symptoms (Cohen's r =.17), and an absence of effects on anxiety/depression symptoms. Remaining outcome indices were subject to selective reporting and/or small sample size bias. Discussion: Our findings underscore the importance of incorporating treatment engagement approaches in the treatment of eating disorders. Optimal reporting of study findings and improving study quality would improve future efforts to obtain an in‐depth understanding of the relationship between motivation and eating disorder symptoms. [ABSTRACT FROM AUTHOR]

Objective: People who are ill with anorexia nervosa (AN) show altered availability of key plasma nutrients. However, little is known about the patterning of alterations that occurs across diverse nutrients during active phases of illness or about the persistence of any such alterations following remission of illness. Method: We compared plasma levels of one‐carbon metabolism nutrients across women with active AN (AN‐Active: n = 53), in remission from AN (AN‐Remitted: n = 40), or who had no eating‐disorder history (NED: n = 36). We also tested associations between body mass index (BMI) changes and changes in pre‐ to posttreatment nutrient levels, and explored the association between nutrient levels, on the one hand, and BMI and eating symptoms, on the other. Choline, betaine, and methionine were analyzed using mass spectrometry. Folate and B12 were analyzed using the AccuBind® ELISA kit. Eating‐disorder symptoms were assessed by interview and self‐report. Results: Compared to NED individuals, AN‐Active individuals exhibited significantly elevated B12 and (less‐reliably) betaine. In AN‐Active individuals, lower BMI was associated with higher B12. Discussion The observed alterations run contrary to the intuition that plasma nutrient levels should be directly responsive to nutritional status and suggest, instead, the existence of compensatory adaptations to malnutrition in individuals with active AN. Further study is required to clarify mechanisms that underlie such effects. [ABSTRACT FROM AUTHOR]

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. Plain English summary: The COVID-19 pandemic has had significant impacts for children, youth and families with eating disorders (EDs) and those who care for them. The objective of this study was to understand the impacts on financial and personal costs to youth, caregivers and clinicians when either accessing or delivering ED services during the pandemic. This study consisted of an online survey and discussion groups with youth (16-25 years old) with lived experience of an ED, primary caregivers, clinicians and decision-makers delivering ED services to understand the costs they experienced. Although many reported costs were financial, including direct medical costs (i.e. private therapy) and direct non-medical costs (i.e. transportation, accommodation costs), there were also significant personal costs to individuals and their families. Healthcare professionals also reported extensive challenges with resources and increased work expectations due to the pandemic context. Acknowledging the costs experienced by young people, families and healthcare professionals during the pandemic allows for the discussion of how we can better support those accessing or delivering ED services in times of crisis and non-crisis. [ABSTRACT FROM AUTHOR]

Background: This study explored state-related tendencies in DNA methylation in people with anorexia nervosa. Methods: We measured genome-wide DNA methylation in 75 women with active anorexia nervosa (active), 31 women showing stable remission of anorexia nervosa (remitted) and 41 women with no eating disorder (NED). We also obtained postintervention methylation data from 52 of the women from the active group. Results: Comparisons between members of the active and NED groups showed 58 differentially methylated sites (Q < 0.01) that corresponded to genes relevant to metabolic and nutritional status (lipid and glucose metabolism), psychiatric status (serotonin receptor activity) and immune function. Methylation levels in members of the remitted group differed from those in the active group on 265 probes that also involved sites associated with genes for serotonin and insulin activity, glucose metabolism and immunity. Intriguingly, the direction of methylation effects in remitted participants tended to be opposite to those seen in active participants. The chronicity of Illness correlated (usually inversely, at Q < 0.01) with methylation levels at 64 sites that mapped onto genes regulating glutamate and serotonin activity, insulin function and epigenetic age. In contrast, body mass index increases coincided (at Q < 0.05) with generally increased methylation-level changes at 73 probes associated with lipid and glucose metabolism, immune and inflammatory processes, and olfaction. Limitations: Sample sizes were modest for this type of inquiry, and findings may have been subject to uncontrolled effects of medication and substance use. Conclusion: Findings point to the possibility of reversible epigenetic alterations in anorexia nervosa, and suggest that an adequate pathophysiological model would likely need to include psychiatric, metabolic and immune components. [ABSTRACT FROM AUTHOR]

Objective: The relationship between eating disorders (EDs) and substance use (SU) has only been briefly described in literature using mainly adult populations. This study examined the prevalence and characteristics of SU among patients of an adolescent ED outpatient treatment program. Method: A retrospective chart analysis was conducted to determine and subsequently compare medical status, psychosocial factors, treatment course and outcome between patients with and without SU. Results: Over 60% of patients with SU status (n = 203) reported regularly consuming substances. 33.4% of substance users received a diagnosis involving purging behaviors compared to 5.9% of nonusers. Females composed 96.4% and 81.7% of users and nonusers, respectively. Users reported significantly more self‐harm (57.7% of users vs. 38.6% of nonusers) but did not differ significantly in terms of trauma (abuse or victimization; 48.3% of users vs. 44.9% of nonusers). The percentage of ideal body weight significantly improved throughout treatment and did not differ by SU with a mean increase of 5.29% (SD = 13.6) among nonusers compared to 5.45% (SD = 7.5) of users. While users and nonusers did not differ before and after treatment in ED severity, users were more likely than nonusers to drop‐out of treatment (41.5% of users vs. 25.2% of nonusers). Discussion: Adolescents with SU benefit from ED outpatient treatment as much as those without SU, however, users are more likely to drop‐out. Therefore, treatment should target these adolescents' emotional dysregulation to improve treatment compliance. Further research is necessary to determine the efficacy of such an approach. [ABSTRACT FROM AUTHOR]

Background and Objectives: Depression has been associated with alterations in social functioning. Decoding and understanding others' mental states and adaptive reasoning are important for social functioning. This study examined theory of mind (ToM) and socio-moral reasoning (SMR) in adolescent girls with and without depression. Within the depression group, we examined associations between relevant clinical features (depression severity, anxiety symptoms and borderline personality traits) and ToM and SMR.Methods: A cross-sectional study was conducted, whereby 43 adolescent girls (mean age = 16.19, SD = 1.24) meeting full or subthreshold criteria for depression and 40 adolescent girls (mean age = 15.44, SD = 1.24) with no psychiatric diagnosis were recruited. ToM was assessed using the Movie for the Assessment of Social Cognition; SMR was evaluated via the Socio-Moral Reasoning Aptitude Level task.Results: Analyses of covariance indicated that adolescents with depression did not differ from controls in ToM abilities but showed lower socio-maturity scores on the SMR task. This difference disappeared after controlling for the number of words used to justify responses. Amongst adolescents with depression, multiple linear regression analyses revealed that higher levels of borderline personality traits were associated with lower levels of mentalization (ToM task), and more severe depressive symptoms were associated with lower socio-moral maturity stages (SMR task) LIMITATIONS: Directional associations were not studied, and the sample included only girls.Conclusions: Findings may help to explain clinical heterogeneity in social cognitive functioning observed in individuals with depression. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Evidence associates anorexia nervosa (AN) with epigenetic alterations that could contribute to illness risk or entrenchment. We investigated the extent to which AN is associated with a distinct methylation profile compared to that seen in normal-eater women. Method Genome-wide methylation profiles, obtained using DNA from whole blood, were determined in 29 women currently ill with AN (10 with AN-restrictive type, 19 with AN-binge/purge type) and 15 normal-weight, normal-eater control women, using 450 K Illumina bead arrays. Results Regardless of type, AN patients showed higher and less-variable global methylation patterns than controls. False Discovery Rate corrected comparisons identified 14 probes that were hypermethylated in women with AN relative to levels obtained in normal-eater controls, representing genes thought to be associated with histone acetylation, RNA modification, cholesterol storage and lipid transport, and dopamine and glutamate signaling. Age of onset was significantly associated with differential methylation in gene pathways involved in development of the brain and spinal cord, while chronicity of illness was significantly linked to differential methylation in pathways involved with synaptogenesis, neurocognitive deficits, anxiety, altered social functioning, and bowel, kidney, liver and immune function. Discussion Although pre-existing differences cannot be ruled out, our findings are consistent with the idea of secondary alterations in methylation at genomic regions pertaining to social-emotional impairments and physical sequelae that are commonly seen in AN patients. Further investigation is needed to establish the clinical relevance of the affected genes in AN, and, importantly, reversibility of effects observed with nutritional rehabilitation and treatment. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015; 48:874-882) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Longitudinal epidemiological studies with birth cohorts have shown that physical aggression in humans does not appear suddenly in adolescence as commonly thought. In fact, physically aggressive behaviour is observed as early as 12 months after birth, its frequency peaks around 2 - 4 years of age and decreases in frequency until early adulthood. However, a minority of children (3-7%) maintain a high frequency of physical aggression from childhood to adolescence and develop serious social adjustment problems during adulthood. Genetic factors and early social experiences, as well as their interaction, have been shown to play an important role in the development of chronic aggressive behaviour. However, the biological mechanisms underlying these associations are just beginning to be uncovered. Recent evidence suggests that epigenetic mechanisms are responsive to adverse environments and could be involved in the development of chronic aggression. Using both gene candidate and genomic approaches, recent studies have identified epigenetic marks, such as DNA methylation alterations in genes involved in the stress response and the serotonin and immune systems to be partly responsible for the long-lasting effects of early adversity. Further longitudinal studies with biological, environmental and behavioural assessments from birth onwards are needed to elucidate the sequence of events that leads to these long-lasting epigenetic marks associated with early adversity and aggression. [ABSTRACT FROM AUTHOR]

Background: Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development. Methods: Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists. Results: Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region-specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms. Limitations: There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain. Conclusion: A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology. [ABSTRACT FROM AUTHOR]

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) use may have long-term neurotoxic effects. In this study, positron emission tomography with the tracer alpha-[11C]methyl-Ltryptophan (11C-AMT) was used to compare human brain serotonin (5-HT) synthesis capacity in 17 currently drug-free MDMA polydrug users with that in 18 healthy matched controls. Gender differences and associations between regional 11C-AMT trapping and characteristics of MDMA use were also examined. MDMA polydrug users exhibited lower normalized 11C-AMT trapping in pre-frontal, orbitofrontal, and parietal regions, relative to controls. These differences were more widespread in males than in females. Increased normalized 11C-AMT trapping in MDMA users was also observed, mainly in the brainstem and in frontal and temporal areas. Normalized 11C-AMT trapping in the brainstem and prefrontal regions correlated positively and negatively, respectively, with greater lifetime accumulated MDMA use, longer durations of MDMA use, and shorter time elapsed since the last MDMA use. Although the possibility of pre-existing 5-HT alterations pre-disposing people to use MDMA cannot be ruled out, regionally decreased 5-HT synthesis capacity in the forebrain could be interpreted as neurotoxicity of MDMA on distal (frontal) brain regions. On the other hand, increased 5-HT synthesis capacity in the raphe and adjacent areas could be due to compensatory mechanisms. [ABSTRACT FROM AUTHOR]

The functioning of the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic (5-HT) system are known to be intertwined with mood. Alterations in these systems are often associated with depression. However, neither are sufficient to cause depression in and of themselves. It is now becoming increasingly clear that the environment plays a crucial role, particularly, the perinatal environment. In this review, we posit that early environmental stress triggers a series of epigenetic mechanisms that adapt the genome and programme the HPA axis and 5-HT system for survival in a harsh environment. We focus on DNA methylation as it is the most stable epigenetic mark. Given that DNA methylation patterns are in large part set within the perinatal period, long-term gene expression programming by DNA methylation is especially vulnerable to environmental insults during this period. We discuss specific examples of genes in the 5-HT system (serotonin transporter) and HPA axis (glucocorticoid receptor and arginine vasopressin enhancer) whose DNA methylation state is associated with early life experience and may potentially lead to depression vulnerability. We conclude with a discussion on the relevance of studying epigenetic mechanisms in peripheral tissue as a proxy for those occurring in the human brain and suggest avenues for future research. [ABSTRACT FROM AUTHOR]

Summary: Background: Testosterone is the key hormone for the development of male reproductive organs and secondary sexual characteristics. In addition, testosterone is associated with behavioural traits, including sexual behaviour and social dominance. The level of circulating testosterone in the human body is determined by genetic and environmental factors. Twin studies have shown moderate to high heritability in adolescence and adulthood, but heritability in early childhood has not been investigated. This study aimed at disentangling the genetic and environmental contributions to testosterone levels soon after birth. Methods: Using a sample of 314 twin pairs, saliva testosterone levels were measured at 5 months after birth. Quantitative genetic modelling was used to assess genetic and environmental contributions to the variation in testosterone levels. Results: Variation in testosterone levels was explained by common (56.6%) and unique (43.4%) environmental factors. Conclusions: Taken together, these data from the largest study of twin testosterone levels suggest that, in contrast to findings in adulthood, environmental factors determine the interindividual variability in testosterone levels in early infancy. This may have consequences for the development of sex-related behaviour during childhood and calls for studies designed to unravel specific genetic and environmental factors involved in this process. [ABSTRACT FROM AUTHOR]

Abstract: There is an increasing evidence that prenatal and early postnatal stressors have life long impacts on physical and mental health problems. Animal studies have shown that this could include enduring changes to brain serotonin neurotransmission. In the present study, we tested whether perinatal adversity in humans has a long-term impact on brain serotonin neurotransmission in adulthood. Twenty-six healthy males, recruited from a 27-year longitudinal study, underwent a positron emission tomography scan with the tracer alpha-[11C]methyl-l-tryptophan (11C-AMT), as an index of serotonin synthesis capacity. The trapping constant is taken as a proxy for the regional 5-HT synthesis. Birth complications, especially a delivery where the fetus showed signs of physiological distress, predicted lower 11C-AMT trapping in the hippocampus and medial orbitofrontal cortex. Lower 11C-AMT trapping in the medial orbitofrontal cortex was also predicted by maternal smoking and lower birth weight. There were no effects of childhood or recent adversity. This is the first human study reporting associations between perinatal adversity and adult 11C-AMT trapping in the hippocampus and medial orbitofrontal cortex. The associations suggest that limbic serotonin pathways may be particularly vulnerable to environmental challenges during the period when they undergo the most prominent neurodevelopmental changes. In combination with other risk factors, perinatal stressors may contribute to increased vulnerability for psychiatric disorders in which serotonin plays a major role. [Copyright &y& Elsevier]

Negative affect in healthy populations regulates the appraisal of demanding situations, which tunes subsequent effort mobilization and adjustments in cognitive control. In the present study, we hypothesized that dysphoria in depressed individuals similarly modulates this adaptation, possibly through a neural mechanism involving serotonergic regulation. We tested the effect of dysphoria induced by acute tryptophan depletion (ATD) in remitted depressed patients on conflict adaptation in a Simon task. ATD temporarily lowers the availability of the serotonin precursor L-Tryptophan and is known to increase depressive symptoms in approximately half of remitted depressed participants. We found that depressive symptoms induced by ATD were associated with increased conflict adaptation. Our finding extends recent observations implying an important role of affect in regulating conflict-driven cognitive control. [ABSTRACT FROM AUTHOR]

Abstract: Acute tryptophan depletion (ATD) in currently depressed patients has no immediate effect on symptoms, but leads to transient symptom improvement or worsening the next day. In view of recent findings concerning the cognitive effects of serotonin manipulations, we used ATD in fourteen depressed patients to investigate whether cognitive effects following ATD predict symptom changes. We found that symptom improvement 24h after ATD was associated with an improved recall of positive words and with less attentional bias and recall of negative words, 5h after ATD. These results indicate that serotonergic alterations affect emotional processing which may subsequently lead to symptom changes. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methodology/Principal Findings: In the present study, positron emission tomography with the tracer alpha-[11C]methyl-Ltryptophan (11C-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 (CLHPA; N = 8) and individuals with normal (low) patterns of physical aggression (LPA; N = 18). The C-LHPA males had significantly lower trapping of 11C-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. Conclusions/Significance: 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. [ABSTRACT FROM AUTHOR]

Depressive disorders are associated with various cognitive impairments. Studies on whether or not these impairments persist into the euthymic phase have shown conflicting results, due to differences in test versions and in study samples. In this paper, we aimed to compare the cognitive performance of remitted depressed patients with that of age- and gender-matched healthy volunteers across a wide range of cognitive domains. In two studies, we found few differences on neutral as well as emotional information processing tests. The findings indicate that remitted depressed patients who use antidepressant medication still show an increased recognition of facial expression of fear compared to healthy controls. Patients also performed worse on a test of recognition of abstract visual information from long-term memory. No other residual cognitive impairments were found. These results indicate that most of the cognitive impairments associated with depression resolve with recovery through medication, even when recovery is incomplete. Considering the finding that remitted depressed patients have higher levels of cognitive reactivity, future studies may investigate the possibility that these cognitive impairments have not resolved but have become latent, and may therefore easily be triggered by small changes in mood state. Depression and Anxiety 0:1–10, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Cognitive reactivity (CR) is a psychological vulnerability marker of depression, whereas response to acute tryptophan depletion (ATD; a serotonergic challenge procedure) is a biological vulnerability marker. The aim of this study was to investigate the relationship between these markers. Thirty-nine remitted depressed patients participated in 2 ATD sessions in a double-blind crossover design. CR, assessed prior to the ATD sessions, predicted depressive response to high-dose ATD. CR also diminished the effects of 2 known predictors of ATD response: gender and residual symptoms. Neuroticism and behavioral inhibition were unrelated to ATD response. CR is associated with an increased sensitivity to reductions of serotonin concentrations. These findings present a small step toward unifying cognitive and neurobiological theories of depression. [ABSTRACT FROM AUTHOR]

Background: Depression is a major risk factor for cardiovascular disease. An important risk factor for cardiovascular disease, low heart rate variability, often has been found in depressed patients and has been associated with impulsivity. The present study investigated whether experimental lowering of serotonin would decrease heart rate variability and increase impulsivity in remitted depressed patients, in particular in those patients with disturbed impulse control. Methods: Nineteen patients in remission from depression received high-dose and low-dose acute tryptophan depletion in a randomized, counterbalanced, double-blind crossover design. Heart rate variability and impulsivity were assessed during each acute tryptophan depletion session and during a baseline session. Suicidal ideation during past depression was used as an index for individual differences in impulse control. Results: High-dose acute tryptophan depletion led to a larger increase in depressive symptoms than did low-dose acute tryptophan depletion. High-dose acute tryptophan depletion decreased heart rate variability and increased impulsivity and anxiety, but only in patients with a history of suicidal ideation. Symptom effects of high-dose acute tryptophan depletion correlated with low heart rate variability at baseline. Conclusions: Depressed patients who have problems with controlling impulsivity might be more at risk for developing cardiovascular disease, possibly related to increased vulnerability to impaired 5-hydroxytryptamine function. [Copyright &y& Elsevier]

Depression is associated with reduced brain serotonin (5-hydroxytryptamine; 5-HT) function and with cognitive dysfunctions. A diet rich in α-lactalbumin protein has been found to increase the ratio tryptophan/large neutral amino acids (Trp/∑LNAA), and to improve cognitive functioning in individuals with high neuroticism scores. Since cognitive dysfunctions sometimes persist after remission of depression, the present study investigated the effects of α-lactalbumin-enriched diet on cognition in recovered depressed patients. Twenty-three recovered depressed patients and 20 healthy matched controls without a history of depression consumed meals rich in α-lactalbumin or casein protein in a double-blind crossover design. Mood, cognitive function and plasma amino acids were assessed at both sessions before and after dietary intake. Alpha-lactalbumin protein had no effect on mood, but improved abstract visual memory and impaired simple motor performance. These effects were independent of history of depression. Supplements of α-lactalbumin may be useful for nutrition research in relation to age- or disease-related memory decline. The present findings should be further examined in different (e.g. medicated) samples. The long-term effects of α-lactalbumin should also be investigated. [ABSTRACT FROM AUTHOR]

Abstract: Background: It has frequently been demonstrated that experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50–60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression. In unmedicated depressed patients, ATD has no immediate effect on symptoms. The effects in currently depressed medicated patients have not been investigated. Methods: Fourteen currently depressed patients (seven patients treated with a selective serotonin–noradrenalin reuptake inhibitor (SSNRI); seven other treatment, non-SSNRI) received ATD in a double-blind, crossover design. Different strengths of the ATD mixture (aimed at 50% and 90% reduction of tryptophan) were used on separate days. Psychiatric symptoms were assessed at both sessions prior to, at +6.5 h, and at +24 h after ATD. Results: The ATD mixtures induced the expected reductions of plasma tryptophan levels. Full but not partial depletion improved mood and other psychiatric symptoms at +24 h in patients who received SSNRI treatment, as indicated by clinical ratings and self-report. Subjective sleep quality also improved. Conclusions: The effects of ATD on psychiatric symptoms in currently depressed patients are remarkably different from the results in recently remitted SSRI-treated patients. ATD in currently depressed patients treated with serotonergic antidepressants possibly provides important information about the mechanism of action of SSRIs. [Copyright &y& Elsevier]

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on cognitive processes in remitted depressed patients have not been investigated. The aim of the present study was to investigate the effects of different extents of depletion on mood and cognitive tasks involving neutral and emotional stimuli. Twenty patients in remission or in partial remission from depression received ATD in a double-blind, crossover design. Mood was assessed at both sessions before, at +6.5 h and +24 h after depletion. Cognitive assessment in both sessions started at +4.75 h, and also before and after the whore procedure. The ATD mixtures induced the expected reductions of plasma tryptophan levels. High-dose ATD induced a depressive response in a subsample of patients and impaired the processing of positive information independent of mood change. Attention for neutral stimuli (Stroop interference) improved in a dose-dependent manner. ATD may affect mood and cognition via different pathways: one implicated in mood regulation and the processing of emotional information, and one for the processing of neutral information. The first pathway may be more important for discriminating vulnerability to impaired serotonin function. The comparison of the effects of high-dose and low-dose ATD is useful for those studies aiming to investigate the relationships among 5-HT, mood and cognition. [ABSTRACT FROM AUTHOR]

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled (‘mega-analysis’) in order to investigate the mediating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode. [Copyright &y& Elsevier]

• Adolescents with depression were marginally faster than those in the comparison group to recognise sadness, although this trend disappeared once covarying for age and use of antidepressant medication. • Within the depression group, severity of depression symptoms and borderline personality features were associated with poorer emotional facial expression recognition (EFER) performance. • Discrepancies between group and within-group differences may explain some of the clinical heterogeneity observed in studies of EFER amongst adolescents with depression. • Studying clinical features in relation to EFER in adolescents with depression allows for a more nuanced understanding of social difficulties that may be experienced in depression. Studies have reported that emotional facial expression recognition (EFER) may be altered in individuals with depression. This study examined EFER in adolescent girls with and without depression and further examined associations between relevant clinical features of depression and EFER. Fifty adolescent girls aged 12 to 19 years old meeting criteria for depression or subthreshold levels of symptomatology and 55 adolescent girls with no psychiatric diagnosis completed EFER tasks. Reaction time and accuracy for recognising expressions at high and low intensities, and sensitivity in recognising happiness, sadness, anger and fear were assessed. Data were analysed using linear mixed models. Adolescents with depression were marginally faster than those in the comparison group to recognize sadness, although this trend disappeared once covarying for age and antidepressant use. Amongst adolescents with depression, clinical features were associated with poorer EFER performance. In contrast, anxiety symptoms were linked to better accuracy and heightened sensitivity towards happiness. A better understanding of EFER in adolescent girls with and without depression, and how clinical features might be associated with altered patterns of EFER could help to explain clinical heterogeneity observed in such studies of adolescents with depression. Knowledge of socio-cognitive alterations associated with depression will help to better develop and tailor interventions. [ABSTRACT FROM AUTHOR]

• Prenatal PBDE exposure can interfere with children's neurodevelopment. • PBDE blood concentrations in Canada are less than half those in the U.S.A. • We measured PBDEs in maternal blood and assessed IQ for 592 3-year-old children. • Prenatal PBDE exposure was related to lower IQ scores, but only among boys. • It suggests sex-specific neurotoxicity at the low PDBE levels in Canada. 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. To examine the prospective association between prenatal PBDE exposure and cognitive ability in young children, as well as potential sex differences. 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. 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. 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 FROM AUTHOR]

Epigenetic mechanisms are believed to link environmental exposures to alterations in gene expression, and in so doing, to provide a physical substrate for the activation of hereditary potentials by life experiences. In keeping with this idea, accumulating data suggest that epigenetic processes are implicated in eating-disorder (ED) etiology. This paper reviews literature on putative links between epigenetic factors and EDs, and examines ways in which epigenetic programming of gene expression could account for gene-environment interactions acting in the EDs. The paper also presents evidence suggesting that epigenetic processes link malnutrition and life stresses (gestational, perinatal, childhood, and adult) to risk of ED development. Drawing from empirical evidence and clinical experience, we propose that an epigenetically informed understanding of ED etiology can benefit patients, caregivers, and clinicians alike, in the sense that the perspective can reduce judgmental or blameful attitudes on the part of clinicians and caregivers, and increase self-acceptance and optimism about recovery on the part of those affected. [ABSTRACT FROM AUTHOR]

Background: Acute tryptophan depletion (ATD) induces depressive symptoms in remitted depressed patients treated with serotonergic medications, but not in patients treated with noradrenergic medications or electroconvulsive therapy. A recent study suggests that cognitive therapy (CT) protects against the effects of ATD, but the evidence is questionable. The present study compared the effect of ATD in patients who were treated with antidepressant medication and CT (n = 17) versus antidepressant medication alone (n = 23) during their latest episode. Methods: Forty remitted depressed patients underwent high-dose and low-dose ATD in a randomized double-blind crossover design. Results: There were no differences in response to ATD between treatment groups. This applied to groups defined by lifetime and by recent CT experience. Conclusions: Cognitive therapy does not protect against the effects of rapidly lowered plasma tryptophan levels in remitted depressed patients who are also treated with antidepressant medication. [Copyright &y& Elsevier]

Objective: This study aimed to quantify the prevalence of non‐suicidal self‐injury across eating disorders (EDs) and within diagnostic categories through systematic review and proportional, or so‐called prevalence, meta‐analysis. Method: Included studies had to contain individuals with a verified diagnosis of an ED. The last literature search was conducted on September 11, 2023, for studies published on or before September 2023 without a restriction on earliest publication year. Results were synthesized and analyzed using the "metaprop" package in R and presented using forest plots. Bias was assessed by a Peters' regression test and funnel plot. Results: 79 studies published between 1985 and 2023 were included encompassing 32,334 individuals with an ED. Importantly, 42 studies were not included in any other meta‐analyses on self‐injury in EDs to date. Overall prevalence of non‐suicidal self‐injury was 34.59% (95%CI = 30.49–38.81). Prevalence in anorexia nervosa restrictive type, binge/purge type, bulimia nervosa, binge eating disorder and other specified feeding/eating disorder were 23.19% (95%CI = 16.96–30.03%), 41.98% (95%CI = 32.35–51.91%), 36.97% (95%CI = 30.69–43.46%), 21.21% (95%CI = 14.93–28.12%) and 37.65% (95%CI = 28.59–47.09%), respectively. Prevalence estimations could not be estimated for other ED categories due to lack of a sufficient number of studies. Discussion: Non‐suicidal self‐injury is prevalent across both binge/purge and restrictive EDs. Considering the transdiagnostic nature of self‐injurious behaviors in ED, the results highlight the importance of assessment and monitoring of self‐injury in people with ED, irrespective of specific diagnoses. The method of determining self‐injury varied across studies and may limit this study. Public Significance: This study highlights the prevalence of self‐injury across eating disorders irrespective of diagnosis and within specific EDs. While diagnoses known to exhibit self‐injurious behaviors (e.g., bulimia nervosa, anorexia nervosa binge/purge subtype) demonstrated the highest prevalence of self‐injury, all diagnoses were found to have a prevalence greater than 20%. These findings suggest the importance of assessing and monitoring all individuals with an eating disorder for the presence of self‐injury. [ABSTRACT FROM AUTHOR]

Background: Disrupted sleep quality is one of the proposed mechanisms through which chronic stress may lead to depression. However, there exist significant individual differences in sleep reactivity, which is the extent to which one experiences sleep disturbances in response to stress.Purpose: The aim of the current study was to investigate whether low high-frequency heart rate variability (HRV), as a psychophysiological marker of poor emotional and physiological arousal regulation, predicts stress-related sleep disturbances associated with greater risk of depression symptoms.Methods: Using a chronic caregiving stress model, 125 mothers of adolescents with developmental disorders and 97 mothers of typically developing adolescents had their resting HRV and HRV reactivity recorded and completed a measure of depressive symptoms, as well as a 7 day sleep diary to assess their sleep quality. A moderated mediation model tested whether sleep quality mediated the association between chronic stress exposure and depressive symptoms and whether HRV moderated this mediation.Results: After controlling for participant age, body mass index, ethnicity, socioeconomic status, and employment status, poor sleep quality mediated the association between chronic stress and depressive symptoms. Resting HRV moderated this indirect effect such that individuals with lower HRV were more likely to report poorer sleep quality in the context of chronic stressor exposure, which, in turn, was related to greater depressive symptoms.Conclusions: Lower HRV, a potential biomarker of increased sleep reactivity to stress, is associated with greater vulnerability to stress-related sleep disturbances, which, in turn, increases the risk for elevated depressive symptoms in response to chronic stress. [ABSTRACT FROM AUTHOR]

Objective Cognitive functioning is essential to well-being. Since cognitive difficulties are common in many disorders, their early identification is critical, notably during childhood and adolescence. This scoping review aims to provide a comprehensive literature overview of computerized cognitive test batteries (CCTB) that have been developed and used in children and adolescents over the past 22 years and to evaluate their psychometric properties. Method Among 3192 records identified from three databases (PubMed, PsycNET, and Web of Science) between 2000 and 2021, 564 peer-reviewed articles conducted in children and adolescents aged 3 to 18 years met inclusion criteria. Twenty main CCTBs were identified and further reviewed following PRISMA guidelines. Relevant study details (sample information, topic, location, setting, norms, and psychometrics) were extracted, as well as administration and instrument characteristics for the main CCTBs. Results Findings suggest that CCTB use varies according to age, location, and topic, with eight tools accounting for 85% of studies, and the Cambridge Neuropsychological Test Automated Battery (CANTAB) being most frequently used. Few instruments were applied in web-based settings or include social cognition tasks. Only 13% of studies reported psychometric properties. Conclusions Over the past two decades, a high number of computerized cognitive batteries have been developed. Among these, more validation studies are needed, particularly across diverse cultural contexts. This review offers a comprehensive synthesis of CCTBs to aid both researchers and clinicians to conduct cognitive assessments in children in either a lab- or web-based setting. [ABSTRACT FROM AUTHOR]

Background: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. Objectives: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. Population: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. Preliminary Results: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). Conclusions: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development. [ABSTRACT FROM AUTHOR]

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. Plain English summary: Eating-disorder symptoms, such as body image issues, maladaptive behaviors, and preoccupation with weight, tend to develop in adolescence. However, it is unclear whether early childhood characteristics or behaviours could be indicators of a risk of developing eating-disorder symptoms later. The current study examined the possible link between certain early behaviours (e.g., hyperactivity, childhood eating), early cognitive processes, and eating-disorder symptoms development in a community cohort followed from birth. Results showed that being hyperactive in early childhood predicts higher levels of eating-disorder symptoms at the beginning of adolescence (age 15), and that this is partially explained by a link between being hyperactive, being more rigid in our ways of thinking, and engaging in overeating behaviours. Additionally, more early rigid ways of thinking predicted the increase in symptoms over time. Our results demonstrate possible behaviours and characteristics that could be used to identify children at risk of eating disorders, which in future research could potentially help improve our preventive interventions. [ABSTRACT FROM AUTHOR]

DNA methylation allows for the environmental regulation of gene expression and is believed to link environmental stressors to psychiatric disorder phenotypes, such as anorexia nervosa (AN). The oxytocin receptor (OXTR) gene is epigenetically regulated, and studies have shown associations between OXTR and social behaviours in various samples, including women with AN. The present study examined differential levels of methylation at various CG sites of the OXTR gene in 69 women with active AN (AN‐Active), 21 in whom AN was in remission (AN‐Rem) and 35 with no eating disorder (NED). Within each group, we explored the correlation between methylation and measures of social behaviour such as insecure attachment and social avoidance. Hypermethylation of a number of CG sites was seen in AN‐Active participants as compared with AN‐Rem and NED participants. In the AN‐Rem sample, methylation at CG27501759 was significantly positively correlated with insecure attachment (r =.614, p =.003, permutation Q = 0.008) and social avoidance (r =.588, p =.005, permutation Q = 0.0184). Our results highlight differential methylation of the OXTR gene among women with AN, those in remission from AN, and those who never had AN and provide some evidence of associations between OXTR methylation and social behaviour in women remitted from AN. [ABSTRACT FROM AUTHOR]

Eating disorders have early origins, and there could be a continuum between childhood eating behaviors, such as overeating, and long-term disordered eating, but this remains to be shown. BMI, desire for thinness and peer victimization could influence this continuum, but their interactions are unknown. To fill this gap, the study used data from the Quebec Longitudinal Study of Child Development (N = 1511; 52% girls), in which 30.9% of youth presented a trajectory associated with high disordered eating from 12 to 20 years. The results support an indirect association between overeating at age 5 and disordered eating trajectories, with different mediation processes observed between boys and girls. The findings underscore the importance of promoting healthy body images and eating behaviors among youths. [ABSTRACT FROM AUTHOR]

Highlights • Daily life stress is associated with HPA-axis related gene methylation. • DNA methylation in HPA-axis genes is stable over time in healthy volunteers. • DNA methylation-brain associations are gene and tissue specific. • Measuring methylation in different tissues in the same persons can be recommended. Abstract Environmental factors can influence gene expression via epigenetic modifications such as DNA methylation. DNA methylation levels of regulatory regions in Hypothalamo-Pituitary-Adrenal (HPA) axis-related genes assessed from brain tissues as well as from surrogate, peripheral tissues have been associated with vulnerability to stress-related psychopathologies. Commonly used peripheral samples to assess DNA methylation in living humans are derived from blood, saliva or buccal cells. Although psychiatric epigenetic studies are increasingly relying on peripheral measures of DNA methylation, it is still unknown to what extent methylation patterns across peripheral tissues are associated with each other and with measures of brain processes and behavioural stress. In the present study, with a sample of 51 healthy adults, we assessed cross-tissue correlations of DNA methylation patterns in the glucocorticoid receptor (NR3C1) 1 F promoter and the FK506 Binding Protein 5 (FKBP5) gene intron 7 region using saliva and buccal cell samples, and assessed two-year stability in both tissues in a male subsample (N = 14). We also investigated associations between peripherally-derived DNA methylation and measures of neural function and perceived daily stress, and compared the extent of these associations across tissue samples. DNA methylation cross-tissue correlations were highly significant for FKBP5 , but not significant for NR3C1. DNA methylation in both genes remained stable for two years. Tissue- and gene-specific associations were found for brain resting state connectivity and neural responses to sadness, thereby suggesting that saliva- and buccal cell-derived DNA methylation levels of NR3C1 -1 F and FKBP5 gene regions might differently capture different measures of putatively related brain processes. It was also found that greater buccal cell- (but not saliva-) derived NR3C1 -1 F methylation was associated with lower perceived daily life demands. Results of the present study may inform the design of future epigenetic studies on FKBP5 -intron-7 and NR3C1 -1 F-promoter methylation in relation to neuro-imaging and behavioural measures, and provide insight for the development of peripheral DNA methylation correlates of stress sensitivity and resilience. [ABSTRACT FROM AUTHOR]

Abstract: Eye movement desensitization and reprocessing (EMDR), a form of psychotherapy for individuals with post‐traumatic stress disorder (PTSD), has long been a controversial topic, hampered in part by a lack of understanding of the neural mechanisms that contribute to its remedial effect. Here, we review current theories describing EMDR's potential neurobiological mechanisms of action involving working memory, interhemispheric communication, de‐arousal, and memory reconsolidation. We then discuss recent studies describing the temporal and spatial aspects of smooth pursuit and predictive saccades, which resemble those made during EMDR, and their neural correlates within the default mode network (DMN) and cerebellum. We hypothesize that if the production of bilateral predictive eye movements is supportive of DMN and cerebellum activation, then therapies that shift the brain towards this state correspondingly would benefit the processes regulated by these structures (i.e., memory retrieval, relaxation, and associative learning), all of which are essential components for PTSD recovery. We propose that the timing of sensory stimulation may be relevant to treatment effect and could be adapted across different patients depending on their baseline saccade metrics. Empirical data in support of this model are reviewed and experimental predictions are discussed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]