No relationship between male pubertal timing and depression - new insights from epidemiology and Mendelian randomization.

BACKGROUND: In males, the relationship between pubertal timing and depression is understudied and less consistent than in females, likely for reasons of unmeasured confounding. To clarify this relationship, a combined epidemiological and genetic approach was chosen to exploit the methodological advantages of both approaches. METHODS: Data from 2026 males from a nationwide, representative study were used to investigate the non-/linear relationship between pubertal timing defined by the age at voice break and depression, considering a multitude of potential confounders and their interactions with pubertal timing. This analysis was complemented by Mendelian randomization (MR), which is robust to inferential problems inherent to epidemiological studies. We used 71 single nucleotide polymorphisms related to pubertal timing in males as instrumental variable to clarify its causal relationship with depression based on data from 807 553 individuals (246 363 cases and 561 190 controls) by univariable and multivariable MR, including BMI as pleiotropic phenotype. RESULTS: Univariable MR indicated a causal effect of pubertal timing on depression risk (inverse-variance weighted: OR 0.93, 95%-CI [0.87-0.99)], p = 0.03). However, this was not confirmed by multivariable MR (inverse-variance weighted: OR 0.95, 95%-CI [0.88-1.02)], p = 0.13), consistent with the epidemiological approach (OR 1.01, 95%-CI [0.81-1.26], p = 0.93). Instead, the multivariable MR study indicated a causal relationship of BMI with depression by two of three methods. CONCLUSIONS: Pubertal timing is not related to MDD risk in males.

Differentiating anorexia nervosa and atypical anorexia nervosa with absolute weight cut-offs results in a skewed distribution for premorbid weight among youth.

OBJECTIVE: Anorexia nervosa (AN) and atypical AN are conceptualized as distinct illnesses, despite similar characteristics and sequelae. Whereas DSM-5 differentiates youth with AN and atypical AN by the presence of clinical 'underweight' (i.e., 5th BMI percentile for age-and-sex (BMI%)), we hypothesized that using this weight cut-off to discern diagnoses creates a skewed distribution for premorbid weight. METHOD: Participants included hospitalized youth with AN (n = 165, 43.1%) and atypical AN (n = 218, 56.9%). Frequency analyses and chi-square tests assessed the distribution of premorbid BMI z-scores (BMIz) for diagnosis. Non-parametric Spearman correlations and Stepwise Linear regressions examined relationships between premorbid BMIz, admission BMIz, and weight loss in kg. RESULTS: Premorbid BMIz distributions differed significantly for diagnosis (p < .001), with an underrepresentation of 'overweight/obesity' (i.e., BMI% ≥ 85th) in AN. Despite commensurate weight loss in AN and atypical AN, patients with premorbid 'overweight/obesity' were 8.31 times more likely to have atypical AN than patients with premorbid BMI% < 85th. Premorbid BMIz explained 57% and 39% of the variance in admission BMIz and weight loss, respectively. DISCUSSION: Findings support a homogenous model of AN and atypical AN, with weight loss predicted by premorbid BMI in both illnesses. Accordingly, premorbid BMI and weight loss (versus presenting BMI) may better denote the presence of an AN-like phenotype across the weight spectrum. Findings also suggest that differentiating diagnoses with BMI% < 5th requires that youth with higher BMIs lose disproportionately more weight for an AN diagnosis. This is problematic given unique treatment barriers experienced in atypical AN. PUBLIC SIGNIFICANCE: Anorexia nervosa (AN) and atypical AN are considered distinct conditions in youth, with differential diagnosis hinging upon a presenting weight status of 'underweight' (i.e., BMI percentile for age-and-sex (BMI%) < 5th). In our study, youth with premorbid 'overweight/obesity' (BMI% ≥ 85th) disproportionately remained above this threshold, despite similar weight loss. Coupled with prior evidence for commensurate characteristics and sequelae in both diagnoses, we propose that DSM-5 differentiation of AN and atypical AN inadvertently reinforces weight stigma and may contribute to treatment disparities in atypical AN.

Premorbid body weight predicts weight loss in both anorexia nervosa and atypical anorexia nervosa: Further support for a single underlying disorder.

OBJECTIVE: For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. METHOD: Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. RESULTS: Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. DISCUSSION: Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. PUBLIC SIGNIFICANCE: Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

No evidence for a causal contribution of bioavailable testosterone to ADHD in sex-combined and sex-specific two-sample Mendelian randomization studies.

The higher prevalence of attention-deficit/hyperactivity disorder (ADHD) in males raises the question of whether testosterone is implicated in ADHD risk. However, cross-sectional studies did not identify an association between ADHD and testosterone levels. Mendelian randomization (MR) studies can overcome limitations inherent to association studies, especially of reverse causation and residual confounding. In the current study, sex-combined and sex-specific two-sample MR analyses were conducted to address whether testosterone has a causal influence on ADHD risk. Sex-combined as well as sex-specific target-genetic variants for bioavailable testosterone were derived from a large genome-wide association study (GWAS) on up to 382,988 adult white European UK Biobank study participants. In our sex-specific analyses for ADHD, including data from 14,154 males and 4,945 females with ADHD (17,948 and 16,246 controls respectively), no association between bioavailable testosterone and ADHD risk was found, neither in males (inverse-variance weighted (IVW): beta = 0.09, 95%-CI [-0.10, 0.27]) nor in females (IVW: beta=-0.01, 95%-CI [-0.20, 0.19]). However, in the sex-combined analysis, including 38,691 cases and 186,843 controls, genetically predicted bioavailable testosterone was associated with ADHD risk (IVW: beta = 0.24, 95%-CI [0.09, 0.39]). The inclusion of birth weight and/or SHBG as additional variables in multivariable MR analyses did not alter this result. However, when correcting for potential BMI-driven pleiotropy by a multivariable MR study, all effect estimates for testosterone showed non-significant results. Taken together, no robust evidence for a causal effect of bioavailable testosterone on the risk for ADHD was found.

Does hypoleptinemia trigger entrapment in anorexia nervosa? Etiological and clinical considerations.

Based on the recent observation that human recombinant leptin (r-Met-hu-leptin; metreleptin) may induce a profound alleviation of the complex symptomatology of patients with anorexia nervosa (AN), we examine the implications for our conceptualisation of this eating disorder. Hypoleptinemia as a core endocrine feature of AN serves as a central and peripheral trigger of tissue-specific adaptations to starvation. In this narrative review, we argue that leptin deficiency may explain many of the puzzling features of this eating disorder. Weight loss can be viewed as a two-step process, with only the second step entailing hypoleptinemia and thereby the entrapment characteristic of AN. We discuss the central and peripheral distribution of leptin receptors and consider possible functional implications of hypoleptinemia. We contrast the slow psychological recovery of patients with AN and of people who experienced starvation upon weight recovery with the rapid onset of improvements upon off-label metreleptin treatment. Characteristics of the sex and age dependent secretion of leptin may contribute to the elevated vulnerability of young females to develop AN.

[Genetic Diagnostics in Everyday Clinical Practice in Child and Adolescent Psychiatry: Indications, Framework Conditions, Hurdles, and Proposed Solutions]. / Genetische Diagnostik im klinischen Alltag der Kinder- und Jugendpsychiatrie ­ Indikationen, Rahmenbedingungen, Hürden und Lösungsvorschläge.

Genetic Diagnostics in Everyday Clinical Practice in Child and Adolescent Psychiatry: Indications, Framework Conditions, Hurdles, and Proposed Solutions Abstract: Health insurance covers medically necessary genetic testing in Germany. Diagnostic genetic testing has become increasingly important for child and adolescent psychiatry (CAP), reflected by the rising number of national guidelines relevant to CAP, including genetic testing in the recommended diagnostic work-up. However, implementation of theses guidelines in routine clinical care is lacking. This article provides a concise overview of the relevance of genetic testing in CAP-related national guidelines. It outlines the legal and financial framework for genetic testing in Germany. Furthermore, it points out barriers to implementation and offers potential solutions. It then provides examples from clinical practice highlighting the potential benefits patients and their family members might have from receiving a genetic diagnosis. The article closes by outlining future CAP-relevant areas in which genetic testing may become clinically relevant.

Childhood body mass index and the subsequent risk of anorexia nervosa and bulimia nervosa among women: A large Danish population-based study.

OBJECTIVE: Evidence linking childhood body mass index (BMI) with subsequent eating disorders is equivocal. Potential explanations include different study populations and size, and that anorexia nervosa (AN) and bulimia nervosa (BN) should be studied separately. We examined whether birthweight and childhood BMI were associated with subsequent risk of AN and BN in girls. METHOD: We included 68,793 girls from the Copenhagen School Health Records Register born between 1960 and 1996 with information on birthweight and measured weights and heights obtained from school health examinations at ages 6-15 years. Diagnoses of AN and BN were retrieved from Danish nationwide patient registers. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 355 cases of AN (median age: 19.0) and 273 cases of BN (median age: 21.8). Higher childhood BMI was linearly associated with decreasing risk of AN and increasing risk of BN at all childhood ages. At age 6, the HR for AN was 0.85 (95% CI: 0.74-0.97) per BMI z-score and the HR for BN was 1.78 (95% CI: 1.50-2.11) per BMI z-score. Birthweight >3.75 kg was associated with increased risk of BN compared to a birthweight of 3.26-3.75 kg. CONCLUSION: Higher BMI in girls at ages 6-15 years was associated with decreasing risk of AN and increasing risk of BN. Premorbid BMI could be relevant for the etiology of AN and BN, and in identifying high risk individuals. PUBLIC SIGNIFICANCE: Eating disorders are associated with elevated mortality, especially AN. Using a cohort of Copenhagen school children, we linked information on BMI at ages 6-15 years for 68,793 girls with nationwide patient registers. Low childhood BMI was associated with increased risk of AN, whereas high childhood BMI was associated with increased risk of BN. These findings may assist clinicians in identifying individuals at high-risk of these diseases.

Case report: clinical improvements observed in first off-label metreleptin treatment of a patient with atypical anorexia nervosa.

Off-label metreleptin treatment resulted in cognitive, emotional and behavioral improvements of patients with anorexia nervosa, who presented with hypoleptinemia. We now report a case study of a 16-year-old female patient with atypical anorexia nervosa who was treated off-label with metreleptin for 11 days. She had lost 21 kg over 6 months. Her body mass index at referral for inpatient treatment was 20 kg/m2, her serum leptin level was just within the normal range (2.4 ng/ml). Dosing resulted in prominent improvements of mood and weight phobia entailing a comparatively brief inpatient treatment. The observed improvements are similar to those observed in patients with AN, suggesting overlapping mechanisms with respect to clinical effects induced by elevations of absolute or relative hypoleptinemia. Randomized controlled trials are warranted for both eating disorders.

Perceived impact of the COVID-19 pandemic on child and adolescent psychiatric services after 1 year (February/March 2021): ESCAP CovCAP survey.

In April 2020, the European Society for Child and Adolescent Psychiatry (ESCAP) Research Academy and the ESCAP Board launched the first questionnaire of the CovCAP longitudinal survey to estimate the impact of COVID-19 on child and adolescent psychiatry (CAP) services in Europe. In this brief report, we present the main findings from the second questionnaire of the survey, one year after the COVID-19 pandemic began to hit Europe (i.e., February/March 2021). While service delivery to patients and their families was affected in a major way (reported by 68%) at the beginning of the pandemic, the majority of respondents (59%) in this second survey only reported a minor impact on care delivery. The use of telemedicine remained widespread (91%) but the proportion of CAP services partially closed or transformed to accommodate COVID-19 patients (59% in 2020) dropped to 20%. On the other hand, the perceived impact on the mental health and psychopathology of children and adolescents dramatically increased from "medium" (> 50%) in 2020 to "strong" or "extreme" (80%) in 2021. Four nosographic entities were particularly impacted: suicidal crises, anxiety disorders, eating disorders and major depressive episodes. Accordingly, this was associated with a substantial increase in the number of referrals or requests for assessments (91% reported an increase in 2021 while 61% reported a decrease in 2020). Finally, heads of the CAP departments expressed strong concerns regarding the management of the long-term consequences of this crisis, especially regarding the provision of care in light of the perceived increase in referrals.

The bidirectional relationship of obesity and labor market status - Findings from a German prospective panel study.

BACKGROUND: Given the inconsistent findings regarding associations between obesity and unemployment, our analysis is one of the few that explores bidirectional changes in obesity and unemployment. In our prospective study, we address factors associated with the a. transition into and transition out of obesity, including unemployment, and b. transition into and out of unemployment, including obesity. SUBJECTS AND METHODS: The Labor Market and Social Security-Panel (PASS) consists of two independent, nationally representative German subsamples: residents receiving unemployment benefits (50%) and a representative sample of residents (50%). The sample contains N = 11 361 observations between two measurement points three years apart of N = 8440 individuals participating in two or three waves between 2009 and 2015. We analyzed potential predictors of the transition in and out of obesity and unemployment, including health-related quality of life (HrQoL) and physical activity, using logistic regression models. RESULTS: 1. Transition into obesity: Unemployed participants had a higher probability of exhibiting a body mass index (BMI) ≥ 35 kg/m2 three years later (transition into obesity classes II and III; Exp(B) = 1.5). 2. Transition out of obesity: Unemployment did not predict transition out of obesity. Physical activity at least once weekly increased the probability of no longer having a BMI ≥ 35 kg/m2 three years later (Exp(B) = 2.0). 3. Transition into unemployment: Obesity was not associated with becoming unemployed three years later. Participants with a lower mental HrQoL were more likely to become unemployed (Exp(B) = 0.98). 4. Transition out of unemployment: Unemployed individuals reporting a BMI of 30-34.9 kg/m2 were less likely to leave unemployment (Exp(B) = 0.67). A better physical HrQoL was associated with a higher probability of leaving unemployment (Exp(B) = 1.01). CONCLUSIONS: Obesity does not predict future unemployment, but unemployed individuals with obesity have a lower probability of labor market re-entry. Unemployment increases obesity risk. Interactions between obesity and possible confounding variables and their effect on unemployment warrants further examination.

Low leptin levels are associated with elevated physical activity among lean school children in rural Tanzania.

BACKGROUND: In Sub-Saharan African countries, rapid urbanization and increasing socio-economic status are associated with a transition to decreased physical activity (PA). A more sedentary lifestyle is linked to increased body fat leading to increments in leptin levels. Since rodent and human studies in high-income countries have shown that starvation-induced hypoleptinemia triggers high PA, efforts are warranted to pursue the hypothesis that low leptin levels in lean children of low- and middle-income countries (LMIC) are also associated with high PA. METHODS: In this cross-sectional study, we assessed seven-day PA with triaxial accelerometry (ActiGraph GT3X) among 223 primary school children (9 to 12 years of age) in rural Tanzania. Moderate-to-vigorous PA (MVPA) and total accelerometer counts per day were outcome variables. Leptin was determined using enzyme linked immunosorbent assay tests from dried blood spots. Anthropometric assessments were conducted and food insecurity and socio-demographic data were gathered using semi-structured interviews. RESULTS: In this sample of school children in rural Tanzania, leptin concentrations (median: 0.91 ng/mL, P25: 0.55, P75: 1.69), body mass index z-scores (median: -1.35, P25: -1.93, P75: -0.82), and height-for-age-z-scores (median: -1.16, P25: -1.96, P75: -0.61) were low. In contrast, PA levels were high with a median MVPA time of 119 min/day. Linear regression confirmed that leptin levels were negatively associated with MVPA (beta: -18.1; 95%CI: -29.7; -6.5; p = 0.002) and total accelerometer counts (beta: -90,256; 95%CI: -154,146; -26,365; p = 0.006). Children residing in areas with better infrastructure had lower MVPA levels (p < 0.001) and tended to have higher leptin levels (p = 0.062) than children residing in areas only reachable via dirt roads. CONCLUSION: Our cross-sectional field study is the first that supports the hypothesis of low leptin levels as a potential endocrine trigger of high PA in lean children of a LMIC. We observed early signs of a PA transition towards a less active lifestyle in a subgroup residing in areas with better infrastructure that concomitantly tended to have higher leptin concentrations. Considering that area-dependent PA differences were more pronounced among girls than boys, whereas differences in leptin levels were less pronounced, not only biological, but also external factors explain PA transition.

ESCAP CovCAP survey of heads of academic departments to assess the perceived initial (April/May 2020) impact of the COVID-19 pandemic on child and adolescent psychiatry services.

In April 2020, the European Society for Child and Adolescent Psychiatry (ESCAP) Research Academy and the ESCAP Board launched the first of three scheduled surveys to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on child and adolescent psychiatry (CAP) services in Europe and to assess the abilities of CAP centers to meet the new challenges brought on by the crisis. The survey was a self-report questionnaire, using a multistage process, which was sent to 168 heads of academic CAP services in 24 European countries. Eighty-two responses (56 complete) from 20 countries, representing the subjective judgement of heads of CAP centers, were received between mid-April and mid-May 2020. Most respondents judged the impact of the crisis on the mental health of their patients as medium (52%) or strong (33%). A large majority of CAP services reported no COVID-19 positive cases among their inpatients and most respondents declared no or limited sick leaves in their team due to COVID-19. Outpatient, daycare, and inpatient units experienced closures or reductions in the number of treated patients throughout Europe. In addition, a lower referral rate was observed in most countries. Respondents considered that they were well equipped to handle COVID-19 patients despite a lack of protective equipment. Telemedicine was adopted by almost every team despite its sparse use prior to the crisis. Overall, these first results were surprisingly homogeneous, showing a substantially reduced patient load and a moderate effect of the COVID-19 crisis on psychopathology. The effect on the organization of CAP services appears profound. COVID-19 crisis has accelerated the adoption of new technologies, including telepsychiatry.

Rapid amelioration of anorexia nervosa in a male adolescent during metreleptin treatment including recovery from hypogonadotropic hypogonadism.

With this case report we support our medical hypothesis that metreleptin treatment ameliorates starvation related emotional, cognitive and behavioral symptomatology of anorexia nervosa (AN) and show for the first time strong effects in a male patient with AN. A 15.9 year old adolescent with severe AN of eight-month duration was treated off-label with metreleptin. Hyperactivity was assessed with accelerometry. Visual analogue scales (VAS), validated self- and clinician rating scales and lab results tracked changes from baseline to end of the 24-day dosing period and a five-month follow-up. Substantial improvements of mood and eating disorder related cognitions and hyperactivity set in after two days of treatment. During dosing, sub-physiological testosterone and TT3 levels normalized; clinically libido reemerged. Weight did not increase substantially during the dosing period. During follow-up target weight was attained; mood did not deteriorate; hyperactivity ceased. The results substantiate the strong effects seen in female cases and underscore the need for a double-blind placebo-controlled trial to confirm the observed strong, multiple and rapid onset beneficial effects of metreleptin in AN.

Comparing randomized controlled trials of outpatient family-based or inpatient multimodal treatment followed by outpatient care in youth with anorexia nervosa: Differences in populations, metrics, and outcomes.

OBJECTIVE: Various approaches exist to treat youth with anorexia nervosa (AN). Family-based treatment (FBT) has never been compared to long inpatient, multimodal treatment (IMT) in a randomized controlled trial (RCT). The aim of this study was to compare data on body weight trajectories, change in eating disorder psychopathology, hospital days and treatment costs in RCTs delivering FBT or IMT. METHOD: Review of RCTs published between 2010 and 2020 in youth with AN, delivering FBT or IMT. RESULTS: Four RCTs delivering FBT (United States, n = 2; Australia, n = 2), one RCT delivering Family Therapy for AN (United Kingdom) and two RCTs delivering IMT (France, n = 1; Germany, n = 1) were identified from previous meta-analyses. The comparison of studies was limited by (1) significant differences in patient baseline characteristics including pretreated versus non-pretreated patients, (2) use of different psychometric and weight measures and (3) different initial velocity of weight recovery. Minimal baseline and outcome reporting standards for body weight metrics and nature/dose of interventions allowing international comparison are needed and suggestions to developing these standards are presented. DISCUSSION: An RCT should investigate, whether FBT is a viable alternative to IMT, leading to comparable weight and psychopathology improvement with less inpatient time and costs.

[Inpatient Schema Therapy for School Avoidance - A Case Study]. / Stationäre Schematherapie bei Schulvermeidung ­ ein Fallbeispiel.

Inpatient Schema Therapy for School Avoidance - A Case Study Abstract. After a short overview of the basic concepts and methods of schema therapy, we report a case study on the inpatient treatment of a 16-year-old youth with depression and chronic school avoidance. The scores on the Schema inventories and Depression questionnaires are compared before vs. after the treatment, and we then discuss the opportunities and limitations of schema therapy with school-avoiding youths.

[Course of School Absenteeism 1.5-3 Years After Initial Evaluation: Symptoms, Psychosocial Functioning, and Help-Seeking Behavior]. / Verlauf von Schulabsentismus 1.5 bis 3 Jahre nach Erstvorstellung: Prädiktoren, psychosoziales Funktionsniveau und Inanspruchnahme von Hilfen.

Course of School Absenteeism 1.5-3 Years After Initial Evaluation: Symptoms, Psychosocial Functioning, and Help-Seeking Behavior Abstract. Objective: To explore the course of patients with school absenteeism 1.5-3 years after their initial evaluation, including symptoms, school attendance, psychosocial functioning, and help-seeking behavior. Method: Of the 237 patients from specialized psychiatric units for youths displaying school absenteeism, we successfully contacted 108 of them 1.5-3 years after initial admission. We conducted a telephone interview with their parents (SDQ, school situation, help-seeking behavior). Among others, we analyzed the extent of school absenteeism, the scales of the Inventory of School Attendance Problems (ISAP; Knollmann et al., 2019), and the quality of school absenteeism (school refusal vs. truancy vs. mixed group) at admission as possible predictors. Results: The patients had received an extensive amount of youth-welfare measures and inpatient, daycare, and outpatient therapy. 46.3 % had elevated values in the SDQ total score at follow-up, mostly because of emotional problems or problems with peers. Psychosocial functioning, including school attendance, was described as poor for only about 30 %. School attendance problems were significantly predicted by having a conduct disorder and elevated scores on the ISAP-scales Aggression, Teacher Problems, and Peer Problems, though the effect sizes were weak. Conclusions: Externalizing symptoms and associated psychosocial problems seem to be predictive of a negative course of school absenteeism. Implications for prospective longitudinal studies are discussed.

Comparison of cardiovascular risk factors between children and adolescents with classes III and IV obesity: findings from the APV cohort.

OBJECTIVE: Obesity is associated with many cardiovascular risk factors (CVRF) in childhood. There is an ongoing discussion whether there is a linear relationship between degree of overweight and deterioration of CVRFs justifying body mass index (BMI) cut-offs for treatment decisions. METHODS: We studied the impact of BMI-SDS on blood pressure, lipids, and glucose metabolism in 76,660 children (aged 5-25 years) subdivided in five groups: overweight (BMI-SDS 1.3 to <1.8), obesity class I (BMI-SDS 1.8 to <2.3), class II (BMI-SDS 2.3-2.8), class III (BMI-SDS > 2.8-3.3), and class IV (BMI-SDS > 3.3). Analyses were stratified by age and sex. RESULTS: We found a relationship between BMI-SDS and blood pressure, triglycerides, HDL cholesterol, liver enzymes, and the triglycerides-HDL-cholesterol ratio at any age and sex. Many of these associations lost significance when comparing children with obesity classes III and IV: In females < 14 years and males < 12 years triglycerides and glucose parameters did not differ significantly between classes IV and III obesity. Prevalence of dyslipidemia was significantly higher in class IV compared to class III obesity only in females ≥ 14 years and males ≥ 12 years but not in younger children. In girls < 14 years and in boys of any age, the prevalences of type 2 diabetes mellitus did not differ between classes III and IV obesity. CONCLUSIONS: Since a BMI above the highest BMI cut-off was not associated consistently with dyslipidemia and disturbed glucose metabolism in every age group both in boys and girls, measurements of CVRFs instead of BMI cut-off seem preferable to guide different treatment approaches in obesity such as medications or bariatric surgery.

A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder.

BACKGROUND: While observational studies revealed an inverse association between serum 25(OH)vitamin D (25(OH)D) and the risk of attention deficit/hyperactivity disorder (ADHD), the causality of this relationship remains unclear. METHODS: We conducted a bidirectional two-sample Mendelian Randomization (MR) study to examine whether 25(OH)D has an effect on the risk to develop ADHD or vice versa. Information on single nucleotide polymorphisms (SNP) associated with serum 25(OH)D was obtained from a genome-wide association study (GWAS) considering phenotype data from 79,366 individuals of European ancestry. Data on risk for ADHD were derived from a GWAS analysis with 20,183 individuals diagnosed with ADHD and 35,191 controls. For our analysis, we considered effect sizes based on the European participants (19,099 cases and 34,194 controls). RESULTS: Single SNP analyses showed a causal effect of vitamin D on ADHD risk for only one SNP (rs12785878, p = 0.024). The overall MR estimates did not reveal a causal effect of 25(OH)D on risk for ADHD. In the reverse analysis, neither any single nor the multi-SNP MR analyses showed a causal effect of ADHD on 25(OH)D. CONCLUSION: Results from this two-sample MR study did not confirm a causal effect of 25(OH)D on ADHD or vice versa. Accordingly, our study does not provide evidence that improving 25(OH)D via supplementation could reduce the risk of developing ADHD.

Age dependency of body mass index distribution in childhood and adolescent inpatients with anorexia nervosa with a focus on DSM-5 and ICD-11 weight criteria and severity specifiers.

Both DSM-5 and ICD-11 have provided weight cut-offs and severity specifiers for the diagnosis of anorexia nervosa (AN) in childhood, adolescence and adulthood. The aims of the current study focusing on inpatients aged < 19 years were to assess (1) the relationship between age and body mass index (BMI; kg/m2), BMI-centiles, BMI-standard deviation scores (BMI-SDS) and body height-SDS at referral, (2) the percentages of patients fulfilling the DSM-5 and ICD-11 weight criteria and severity categories for AN, and (3) the validity of the AN severity specifiers via analysis of both weight related data at discharge and inpatient treatment duration. The German Registry for Anorexia Nervosa encompassed complete data sets for 469 female patients (mean age = 15.2 years; range 8.9-18.9 years) with a diagnosis of AN (n = 404) or atypical AN (n = 65), who were ascertained at 16 German child and adolescent psychiatric hospitals. BMI at referral increased up to age 15 to subsequently plateau. Approximately one tenth of all patients with AN had a BMI above the fifth centile. The ICD-11 specifier based on a BMI-centile of 0.3 for childhood and adolescent AN entailed two equally sized groups of patients. Discharge data revealed limited validity of the specifiers. Height-SDS was not correlated with age thus stunting had no impact on our data. We corroborate the evidence to use the tenth instead of the fifth BMI-centile as the weight criterion in children and adolescents. Weight criteria should not entail major diagnostic shifts during the transition from adolescence to adulthood. The severity specifiers based on BMI or BMI-centiles do not seem to have substantial clinical validity.

[Feeding and eating disorders in ICD-11]. / ICD-11-Sonderserie: Fütter- und Essstörungen in der ICD-11.

Feeding and eating disorders in ICD-11 Abstract. Innovations in ICD-11 include the adoption of a lifespan approach and culture-related guidance for each disorder. We describe the changes made to the chapter Feeding and Eating Disorders and compared them to the ICD-10. In addition to illustrating the revision of the guidelines for each disorder, we also comment on the inclusion of a new set of diagnoses, avoidant/restrictive food intake disorder (ARFID) and binge-eating disorder (BED).