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.

Changes in patterns of eating habits and food intake during the first German COVID-19 lockdown: results of a cross-sectional online survey.

PURPOSE: The COVID-19 pandemic and public measures have a direct impact on the nutrition situation; studies show changes in food consumption, eating behavior or body weight but complex pattern analyses of changes rarely exist. METHODS: During the first German lockdown, a web-based survey was conducted among adults. It included 33 questions about changes in food intake, eating habits and physical activity, as well as anthropometrics and sociodemographic factors. Patterns of change were calculated based on changes in food intake and eating habits using two-step cluster analysis. To identify influencing factors for assignment to the patterns of change, binary logistic regression analyses were performed. RESULTS: Data from 2103 participants (81% female, 40 ± 14 years) were considered for analysis. Increased stockpiling, cooking, and variation in preparation was reported by 50-70%. The constant pattern (C-P, 36%) reported little change besides the above. The health-oriented pattern (HO-P; 37%) reported eating more healthy foods, avoiding unhealthy foods, and eating less and less frequently. The emotional-driven pattern (ED-P; 28%) exhibits higher influence of emotions on eating behavior, less avoidance of unhealthy foods, and increased consumption of sweets, pastries, and alcohol. The odds of changing eating behavior either to HO-P or ED-P were higher in women, people with migration background, younger participants, and increased with BMI categories. CONCLUSION: Both, the ED-P and HO-P, exhibit distinctive reactions in eating habits and food intake when dealing with a distressing experience. In subgroups, these may lead to disturbances in eating behavior and increase the risk for eating disorders and obesity.

Healthcare Professionals' Conflicts When Treating Transgender Youth: Is It Necessary to Prioritize Protection Over Respect?

Increasingly, transgender minors are seeking medical care such as puberty-suppressing or gender-affirming hormone therapies. Yet, whether these interventions should be performed at all is highly controversial. Some healthcare practitioners oppose irreversible interventions, considering it their duty to protect children from harm. Others view minors, like adults, as transgender individuals who must be protected from discrimination. The underlying ethical question is presented as a problem of priority. Is it primarily relevant that minors are involved? Or should decision makers focus on the fact that they treat transgender individuals? The paper explores the relevance for medical practice. We provide results of an interview study with German healthcare professionals. We discuss the general question whether prioritization among different group memberships of the same person is ethically defensible. We conclude that priority conflicts between group memberships of the same person can be deceptive and should be addressed by an intersectional approach. Eventually, we discuss practical implications.

COVID-19: Effects of Pandemic Related Restrictions on Physical Activity, Screen Time, and Mental Well-being in German adolescents.

Objective: To describe the impact of the COVID-19 pandemic-related restrictions (PR) in April and May 2020 on physical activity (PA), sedentary screen time (SST), and mental well-being (MWB) in German adolescents, and to analyze associations between these variables. Methods: The Münster District Government invited all secondary school students (aged 11-17) in the region to take part in the online survey that assessed PA, SST, and MWB. For data analysis, we calculated descriptive statistics and ran linear regression analysis. Results: 1,038 students (627 [60.4%] female; 14.18 [± 1.97] years) were included in the analysis. During the PR, a marked decline in overall PA (p < .001) and a significant increase (p < .001) in SST were observed. One-third of the students reported worrying more and being less satisfied with their lives since PR. A decrease in life satisfaction (ß = -.524, p < .001) as well as an increase in general worrying (ß = -.336, p = .015) were associated with a decrease in PA during PR. Conclusion: The results show that the restrictions led to a decrease in physical activity, which may have detrimental effects on the students' mental and physical health.

[Dialectical BehaviouralTherapy for Adolescent Patients with Anorexia Nervosa]. / Dialektisch Behaviorale Therapie (DBT-A) bei jugendlichen Patient/innen mit Anorexia nervosa.

Dialectical behavioural therapy (DBT) has become the gold standard in the treatment of patients with borderline personality disorder. This therapy includes the combination of stance and techniques, which are characterized by the dialectic of acceptance and change. In the meantime, this method has also been successfully applied to other psychiatric disorders. In the case of anorexia nervosa - a disorder with a tendency to chronification and a considerably increased mortality risk - the work on treatment motivation increases. Traditional concepts in clinics are increasingly being questioned and tested for their suitability for everyday use. Here, DBT offers a set of tools with which positive experiences of effectiveness have already been made in some clinics. Evidence based on randomized controlled trials is still lacking. In this article, the basic principles of DBT treatment for adolescent patients with anorexia nervosa are explained and experiences with the treatment concept are reported.

[Trans* Youth and Young Adults in Healthcare: A Qualitative Study About Experiences, Challenges, andWishes]. / Trans* Jugendliche und junge Erwachsene im Gesundheitswesen: Eine qualitative Interviewstudie über Erfahrungen, Herausforderungen undWünsche.

The number of adolescents who present themselves to the healthcare system due to the aspect of trans* is rising internationally as well as nationally. Studies, especially from the international area, point next to appropriate treatment situations increasingly to aversively experienced situations.These are characterized by lack of knowledge of the professionals, incorrect naming and pronoun naming as well as inappropriate questions and comments. In order to shed light on the situation in Germany, semi-structured interviews were conducted with ten adolescents and evaluated using qualitative content analysis. Overall, a balanced ratio of positive, appropriate and negative, aversive experiences emerged. Themes were gender-sensitive language, ways of interacting, support/networking and knowledge. The adolescents named parental support and connection to self-help groups as supportive instances in dealing with the healthcare system, but also mentioned structural hurdles such as long waiting times. Overall, the adolescents had a positive outlook on the future and would like to see a sensitization of healthcare workers. Educationalmeasures and further training should be implemented in order to meet these wishes and to ensure needs-based care for trans* adolescents.

[Parents Health Care Experiences of a Child or Adolescent with Gender Incongruence and Gender Dysphoria: A Qualitative Study]. / Erfahrungen im Gesundheitswesen von Sorgeberechtigten eines Kindes oder Jugendlichen mit Geschlechtsinkongruenz und Geschlechtsdysphorie: Eine qualitative Studie.

In general, little is known about the experiences of parents of a transgender child or adolescent when seeking health care services. In addition, there is little research on how parents interact with their child in the health care system. International studies show high vulnerability and psychological distress among those children and adolescents who assign themselves to a gender other than the one assigned at birth. Parental support represents a protective factor related to mental health. The aim of this study is to investigate parental interaction processes in medical-psychological treatment settings. For this purpose, guided qualitative interviews were conducted throughout Germany with twelve fathers and mothers of transgender children/adolescents. Most parents faced a number of challenges and barriers to their children's health care. A lack of knowledge and insecurities on the part of the health care practitioners up to psychopathologization of identity were ascertainable. At the same time, accepting, affectionate and supportive encounters were evident from the reports. Furthermore, it was found that the parents took an essential protective and supportive stance towards their children in the treatments. For improved health care, sensitization and education regarding gender variance in childhood and adolescence is necessary for health care practitioners in the health care system. The study can contribute to expanding the scientific discourse on life biographies of young trans* people and their parents.

Increased early motivational response to food in adolescent anorexia nervosa revealed by magnetoencephalography.

BACKGROUND: It remains unclear to what extent reduced nutritional intake in anorexia nervosa (AN) is a consequence of a reduced motivational response to food. Although self-reports typically suggest AN patients have a reduced appetitive response, behavioral and neurophysiological measures have revealed evidence for both increased and reduced attentional biases towards food stimuli. The mechanisms influencing food perception in AN, might be clarified using time-sensitive magnetoencephalography (MEG) to differentiate the early (more automatic processing) stages from the late (more controlled) stages. METHODS: MEG was recorded in 22 partially weight-restored adolescent AN patients and 29 age- and gender-matched healthy control (HC) participants during a rapid serial visual presentation paradigm using 100 high-calorie food, 100 low-calorie food, and 100 non-food pictures. Neural sources of event-related fields were estimated using the L2-Minimum-Norm method and analyzed in early (50-300 ms) and late (350-500 ms) time intervals. RESULTS: AN patients rated high-calorie food as less palatable and reported overall less food craving than HC participants. Nevertheless, in response to food pictures AN patients showed relative increased neural activity in the left occipito-temporal and inferior frontal regions in the early time interval. No group differences occurred in the late time interval. CONCLUSIONS: MEG results speak against an overall reduced motivational response to food in AN. Instead, relative increased early food processing in the visual cortex suggests greater motivated attention. A greater appetitive response to food might be an adaptive mechanism in a state of undernourishment. Yet, this relative increased food processing in AN was no longer present later, arguably reflecting rapid downregulation.

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.

[Nutrition and mental health - how findings from genetic studies can support the identification of dietary effects]. / Ernährungseffekten auf der Spur ­ Wie die Genetik helfen kann, Zusammenhänge zwischen Ernährung und seelischer Gesundheit aufzudecken.

Nutrition and mental health - how findings from genetic studies can support the identification of dietary effects Abstract. Introduction: Numerous studies indicate that dietary interventions could be an important approach to the prevention and treatment of mental disorders. However, conventional nutritional epidemiological approaches (e. g., observational studies and randomized controlled trials, RCTs) have specific limitations to consider when interpreting the results. This article examines whether genetic studies could help to establish a link between diet and the prevention of mental disorders. Furthermore, it examines whether it is possible to draw conclusions about causal relationships. Methods: This narrative review describes various approaches of genetic cross-phenotype studies and presents examples of their applications in nutritional psychiatry. In addition, it discusses specific requirements as well as the strengths and limitations of the respective approaches. Results: To date, in the context of nutritional psychiatry, genetic correlation analyses, look-up analyses, and Mendelian randomization (MR) studies have been used for genetic crossphenotype analyses. Genetic correlation and look-up analyses provide initial evidence of possible overlap between specific mental disorders and metabolic pathways or specific nutrients. MR studies are used for detailed analyses that aim to identify causal relationships. However, MR is based on specific assumptions that must be met and considered when results are interpreted. Conclusion: Genetic cross-phenotype analyses are a useful amendment to conventional nutritional epidemiological research. In particular, positive results from MR studies provide an important fundament for identifying and developing suitable dietary interventions, which in turn increases the chance of success upon testing in subsequent RCTs. Accordingly, genetic cross-phenotype analyses are important instruments for increasing the efficiency in nutritional psychiatric research.

Immunological and behavioral responses to in vivo lipopolysaccharide administration in young and healthy obese and normal-weight humans.

Obesity is associated with an increase prevalence of neuropsychiatric symptoms and diseases, such as depression. Based on the facts that pro-inflammatory cytokines are able to modulate behavior, and that obesity is characterized by a chronic low-grade inflammatory state, inflammation has been hypothesized to contribute to the neuropsychiatric comorbidity in obese individuals. However, a causal link between inflammation and the development of neuropsychiatric symptoms is hard to establish in humans. Here, we used an inflammatory stimulus, i.e. the intravenous injection of lipopolysaccharide (LPS), in a double-blind placebo-controlled design, to determine the vulnerability of obese individuals to inflammation-induced behavioral changes. The hypothesis was that obese individuals would show heightened behavioral response compared to normal-weight subjects for the same inflammatory stimulus, reflecting an increased sensitivity to the behavioral effects of pro-inflammatory cytokines. LPS (dose 0.8 ng/kg body weight, adjusted for estimated blood volume in obese subjects) and placebo (saline) were intravenously injected in 14 obese healthy subjects and 23 normal-weight healthy subjects in a within-subject, randomized, crossover design. LPS administration induced, in both groups, an acute increase in blood concentrations of cytokines (interleukin-6, tumor necrosis factor-α, and IL-10), as well as in body temperature, cortisol, norepinephrine, sickness symptoms, fatigue, negative mood, and state anxiety. There were little differences in the immune and behavioral responses to LPS between obese and normal-weight subjects, but the cortisol response to LPS was strongly attenuated in obese individuals. Higher percentage of body fat was related to a lower cortisol response to LPS. Taken together, the population of young and healthy obese individuals in this study did not exhibit an increased behavioral sensitivity to cytokines, but an attenuated cortisol response to the immune challenge. Future studies will need to determine whether additional physiological and psychological factors interact with the state of obesity to increase the risk for inflammation-induced neuropsychiatric symptoms.

Effect of vitamin D deficiency on depressive symptoms in child and adolescent psychiatric patients: results of a randomized controlled trial.

PURPOSE: While observational studies revealed inverse associations between serum vitamin D levels [25(OH)D] and depression, randomized controlled trials (RCT) in children and adolescents are lacking. This RCT examined the effect of an untreated vitamin D deficiency compared to an immediate vitamin D3 supplementation on depression scores in children and adolescents during standard day and in-patient psychiatric treatment. METHODS: Patients with vitamin D deficiency [25(OH)D ≤ 30 nmol/l] and at least mild depression [Beck Depression Inventory II (BDI-II) > 13] (n = 113) were 1:1 randomized into verum (VG; 2640 IU vitamin D3/d) or placebo group (PG) in a double-blind manner. During the intervention period of 28 days, both groups additionally received treatment as usual. BDI-II scores were assessed as primary outcome, DISYPS-II (Diagnostic System for Mental Disorders in Childhood and Adolescence, Self- and Parent Rating) and serum total 25(OH)D were secondary outcomes. RESULTS: At admission, 49.3% of the screened patients (n = 280) had vitamin D deficiency. Although the intervention led to a higher increase of 25(OH)D levels in the VG than in the PG (treatment difference: + 14 ng/ml; 95% CI 4.86-23.77; p = 0.003), the change in BDI-II scores did not differ (+ 1.3; 95% CI - 2.22 to 4.81; p = 0.466). In contrast, DISYPS parental ratings revealed pronounced improvements of depressive symptoms in the VG (- 0.68; 95% CI - 1.23 to - 0.13; p = 0.016). CONCLUSION: Whereas this study failed to show a vitamin D supplementation effect on self-rated depression in adolescent in- or daycare patients, parents reported less depressive symptoms in VG at the end of our study. Future trials should consider clinician-rated depressive symptoms as primary outcome. TRIAL REGISTRATION: "German Clinical Trials Register" ( https://www.drks.de ), registration number: DRKS00009758.

Incontinence and constipation in adolescent patients with anorexia nervosa-Results of a multicenter study from a German web-based registry for children and adolescents with anorexia nervosa.

OBJECTIVE: Nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) are common disorders in childhood and are frequently accompanied by comorbid psychiatric disorders. Despite a high association between urinary and fecal incontinence with psychiatric and neurodevelopmental disorders, research on comorbidity between incontinence and anorexia nervosa (AN) remains scarce. Yet, it is well known that somatic consequences of AN include metabolic and gastrointestinal disorders. The study sought to assess the prevalence of incontinence and constipation in children and adolescents with AN and to examine associations of these two symptoms with body weight at admission and with BMI changes during inpatient treatment. METHODS: Data collected between 2015 and 2017 by a multicenter German web-based registry for AN were analyzed. Three hundred and forty-eight patients with AN (96.3% female, mean age = 15.1 ± 1.8 years) were assessed regarding AN subtype, psychiatric comorbidity, body weight, incontinence, and constipation. RESULTS: Overall, 27.6% of patients had constipation, 1.8% had NE and 1.8% DUI. Prevalence of constipation did not significantly differ between AN subtypes. Constipation did not lead to any significant differences in weight/BMI changes during inpatient treatment. DISCUSSION: This is the largest study of incontinence and constipation in patients with AN, so far. Our results indicate that constipation is highly prevalent in adolescent patients with AN and reflects a clinically relevant condition. Despite, patients with AN do not have an increased prevalence of incontinence compared with the general population. Future studies should include medical examinations like ultrasound and physical examination of the lower abdomen to evaluate the severity of constipation.

Risk factors for a low weight gain in the early stage of adolescent anorexia nervosa inpatient treatment: findings from a pilot study.

PURPOSE: Body weight restoration is a major treatment aim in juvenile inpatients with anorexia nervosa (AN) (i.e., 500-1000 g/week according to the German guidelines). Several studies suggest the early weight gain to be crucial for remission. The identification of patients at risk of a low early weight gain could enable an adequate adaptation of treatment. Thus, we aimed at detecting risk factors of a low weight gain during inpatient treatment. METHODS: The presented work analyzes data from a pilot study in 30 female adolescent inpatients with AN (restricting subtype; age range at admission: 12.6-17.6 years). Premorbid characteristics, history of symptomatology, anthropometric data, and eating-disorder psychopathology were compared between those who gained at least an average of 500 g/week during the first 7 weeks of treatment (high weight gainers, HWG) and those who did not (low weight gainers, LWG). RESULTS: At admission, LWG (n = 15) had a significantly higher BMI(-SDS) and scored significantly higher in the eating-disorder examination questionnaire (EDE-Q) than HWG (n = 15). A logistic regression analysis indicated both parameters to be independently associated with a low weight gain. CONCLUSION: Higher EDE-Q scores seem to be a major risk factor for a low weight gain at the beginning of treatment. Moreover, a higher BMI(-SDS) at admission does not necessarily indicate a less severe AN symptomatic, as it was associated with a lower weight gain in our sample during the first 7 weeks of treatment. Reassessment of our results in larger studies is required to draw firm conclusions for clinical practice. LEVEL OF EVIDENCE: Level V.

Effect of an vitamin D deficiency on depressive symptoms in child and adolescent psychiatric patients - a randomized controlled trial: study protocol.

BACKGROUND: Depression is a significant health and economic burden worldwide affecting not only adults but also children and adolescents. Current treatment options for this group are scarce and show moderate effect sizes. There is emerging evidence that dietary patterns and specific nutritional components might play a role in the risk for developing depression. This study protocol focusses on the role of vitamin D which is for long known to be relevant for calcium and phosphorous homeostasis and bone health but might also impact on mental health. However, the assessment of the vitamin D status of depressed juvenile patients, or supplementation of vitamin D is currently not part of routine treatment. Controlled intervention studies are indispensable to prove whether a vitamin D deficiency ameliorates depressive symptoms. METHODS/DESIGN: This double blinded, randomized controlled trial will enroll 200 inpatients from a child and adolescent psychiatric department with a vitamin D deficiency defined by a 25(OH)-vitamin D-level < 30 nmol/l (12 ng/ml) and a Beck Depressions Inventory (BDI-II) score > 13 (indicating at least: mild depression). Upon referral, all patients will be screened, checked for inclusion criteria, and those eligible will be randomized after written consent into a supplementation or placebo group. Both study-arms will receive treatment-as-usual for their psychiatric disorder according to established clinical guidelines. The participants of the vitamin D supplementation group will receive 2640 I.E. vitamin D3 q.d. for 28 days in accordance with best practice in pediatric endocrinology. We hypothesize that delaying supplementation of vitamin D in the placebo arm will affect the treatment success of the depressive symptomatology in comparison to the vitamin D supplementation group. Patients will be enrolled for a period of 28 days based on the mean length of hospitalization of juveniles with depression. DISCUSSION: Randomized controlled trials in children and adolescents with depression are needed to elucidate the role of a vitamin D deficiency for mental disorders and to investigate the relevance of a routine assessment and supplementation of vitamin D deficits. TRIAL REGISTRATION: DRKS00009758, 16/06/2016 (retrospectively registered).

Relevance of polymorphisms in MC4R and BDNF in short normal stature.

BACKGROUND: Variation in genes of the leptinergic-melanocortinergic system influence both body weight and height. Because short normal stature (SNS) is characterized by reduced body height, delayed maturation and leanness, allelic variation of genes in this pathway are hypothesized to affect this common condition. METHODS: We analyzed the coding regions of LEP, MC4R, MRAP2 and BDNF in 185 children with SNS (height < 5th percentile) to search for non-synonymous and frameshift variants. For association studies (two-sided χ2-tests) population-based data sets (ExAC, EVS and KORA) were used. Cyclic AMP accumulation, cell surface expression, central expression and MAP kinase activation were assayed in vitro to determine the functional implications of identified variants. RESULTS: We detected eleven variants predicted to be protein-altering, four in MC4R, four in BDNF, and three in MRAP2. No variants were found in LEP. In vitro analysis implied reduced function for the MC4R variant p.Met215Ile. Loss-of-function is contrary to expectations based on obesity studies, and thus does not support that this variant is relevant for SNS. The minor SNP alleles at MC4R p.Val103Ile and BDNF p.Val66Met were nominally associated with SNS. CONCLUSION: Taken together, although genes of the leptinergic-melanocortinergic system are important for normal growth, our data do not support the involvement of rare mutations in LEP, MC4R, MRAP2 or BDNF in short normal stature.

The association of serum leptin levels with food addiction is moderated by weight status in adolescent psychiatric inpatients.

Leptin is essential for the control of energy homeostasis and eating behaviour. We investigated potential associations between serum leptin levels and food addiction in adolescent psychiatric inpatients (n = 228). The most frequent psychiatric diagnoses were mood disorders, anxiety disorders, and substance use disorders. More than three quarters of the study group suffered from more than one psychiatric disorder. Food addiction was assessed with the Yale Food Addiction Scale. Leptin was determined in serum. Analyses were conducted for the whole body weight range and for distinct weight categories to evaluate a potential impact of known nonlinearity between leptin levels and satiety due to leptin resistance in obese. A weak negative association between food addiction and leptin in normal weight patients (ß = -0.11, p = .022) was detected. In contrast, food addiction was associated with a significantly higher serum leptin (ß = 0.16. p = .038) in overweight patients. Food addiction in normal weight patients might be associated with restrained eating, previously shown to involve reduced leptin levels. The small positive association of food addiction with higher serum leptin in overweight patients might reflect leptin resistance and overeating.

Vitamin D and mental health in children and adolescents.

While vitamin D is known to be relevant for bone health, evidence has recently accumulated for an impact on mental health. To identify the potential benefits and limitations of vitamin D for mental health, an understanding of the physiology of vitamin D, the cut-off values for vitamin D deficiency and the current status of therapeutic trials is paramount. Results of a systematic PUBMED search highlight the association of vitamin D levels and mental health conditions. Here, we focus on children and adolescents studies as well as randomized controlled trials on depression in adults. 41 child and adolescent studies were identified including only 1 randomized controlled and 7 non-controlled supplementation trials. Overall, results from 25 cross-sectional studies as well as from 8 longitudinal studies suggest a role of vitamin D in the pathogenesis of mental disorders in childhood and adolescence. Findings from supplementation trials seem to support this hypothesis. However, randomized controlled trials in adults revealed conflicting results. Randomized controlled trials in childhood and adolescents are urgently needed to support the potential of vitamin D as a complementary therapeutic option in mental disorders. Study designs should consider methodological challenges, e.g., hypovitaminosis D at baseline, appropriate supplementation doses, sufficient intervention periods, an adequate power, clinically validated diagnostic instruments, and homogenous, well-defined risk groups.