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Objective: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best‐evidenced substance used off‐label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP‐guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age‐ and disorder‐specific therapeutic reference range. Method: Sixty‐five adolescents with AN (aged 10–18) treated with OLZ (98% female; 97.5% AN‐restricting‐type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. Results: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. Conclusions: OLZ in the hands of specialists is a well‐tolerated and safe treatment adjunct for adolescents with AN. Highlights: Olanzapine in adolescents with anorexia nervosa is a safe and well‐tolerated adjunct to a multidisciplinary inpatient treatment approach using therapeutic drug monitoring.Correlations of dosage and serum levels are high.A preliminary disorder‐ and age‐specific reference range was successfully defined for the first time. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents (n = 138; mean age, 15; range, 7–18 years; 24.6% males) was treated with fluoxetine (10–40 mg/day). Analyses of both the last timepoint and all timepoints (n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208–328 ng/mL (transdiagnostically) and 201.5–306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose–serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults. [ABSTRACT FROM AUTHOR]

In the early 1920s, it was discovered that nutrition is associated with what is known today as Attention-Deficit/Hyperactivity Disorder (ADHD) and that certain foods can worsen the symptoms. In previous studies, approximately 60% of the participants experience at least a 40% reduction in ADHD symptoms after an oligoantigenic diet (OD). The purpose of this study was to evaluate ADHD symptoms in children approximately 3.5 years after completing a 4-week oligoantigenic diet. Among 28 participants who completed the 4-week diet, 21 were re-assessed for this study after 3.5 years. The severity of ADHD symptoms was assessed with the ADHD-Rating-Scale-IV (ARS). Of 21 participants, 14 fulfilled the responder criterion, whereas 7 did not. At follow-up, 28% of the participants were taking medication. The mean ARS total score improved significantly from T1: M = 29.62 (SD = 9.80) to T2: M = 15.86 (SD = 8.56) between the time points before and after the diet (d = −1.91). There was also a lower ARS total score at the follow-up T5: M = 16.00 (SD = 10.52) compared to before the diet (d = −1.17). This study shows that individually adjusted nutrition significantly improved the ADHD symptomatology of the participants long-term. This suggests that an oligoantigenic diet with subsequent individual nutritional recommendations could become an additional treatment option for children with ADHD. [ABSTRACT FROM AUTHOR]

Introduction Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The 'Therapeutic Drug Monitoring (TDM)-VIGIL' study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved ('on-label'), and off-label use in clinical practice. Methods Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. Results 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4–10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). Conclusion Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings. [ABSTRACT FROM AUTHOR]

Sensory features in autism spectrum disorder (ASD) have received increasing interest in clinical work and research during the recent years. With the Sensory Perception Quotient (SPQ), Tavasolli and colleagues have produced a self-rating scale for adults with ASD that measures sensory hyper-sensitivity in different sensory modalities, without also tapping cognitive or motivational aspects that precede or follow autistic sensory experiences. Here, we present the results of a translation of the SPQ to German and its short version as well as their validation in samples of autistic or neuro-typical participants. We, furthermore, present the psychometric properties and validities of Tavasolli's original SPQ-short version as well as an alternative short version based on different psychometric item-selection criteria. We can show here that our alternative SPQ-short version, overlapping with the original short-version in 61% of its items, exhibits superior reliabilities, reasonable concurrent validities with other related measures. It, furthermore, exhibits excellent differentiation between autistic and non-autistic samples, underscoring its utility as a screening instrument in research and a clinical instrument to supplement the ASD diagnostic process. [ABSTRACT FROM AUTHOR]

Background: Brain-derived neurotrophic factor (BDNF) influences brain plasticity and feeding behaviour, and it has been linked to anorexia nervosa in numerous studies. Findings in mostly adult patients point to reduced serum BDNF levels in the acute stage of anorexia nervosa and rising levels with weight recovery. However, it is unclear whether this increase leads to normalization or supranormal levels, a difference that is potentially important for the etiology of anorexia nervosa and relapse. Methods: We measured serum BDNF at admission (n = 149), discharge (n = 130), 1-year follow-up (n = 116) and 2.5-year follow-up (n = 76) in adolescent female patients with anorexia nervosa hospitalized for the first time, and in healthy controls (n = 79). We analyzed associations with body mass index, eating disorder psychopathology and comorbidities. Results: Serum BDNF was only nominally lower at admission in patients with anorexia nervosa compared to healthy controls, but it increased continuously and reached supranormal levels at 2.5-year follow-up. BDNF was inversely associated with eating disorder psychopathology at discharge and positively associated with previous weight gain at 1-year follow-up. Limitations: We compensated for attrition and batch effects using statistical measures. Conclusion: In this largest longitudinal study to date, we found only nonsignificant reductions in BDNF in the acute stage of anorexia nervosa, possibly because of a shorter illness duration in adolescent patients. Supranormal levels of BDNF at 2.5-year follow-up could represent a pre-existing trait or a consequence of the illness. Because of the anorexigenic effect of BDNF, it might play an important predisposing role for relapse and should be explored further in studies that test causality. [ABSTRACT FROM AUTHOR]

Abstract Background To date, there are no empirically validated treatments of good quality for adolescents showing suicidality and non-suicidal self-injurious behavior. Risk factors for suicide are impulsive and non-suicidal self-injurious behavior, depression, conduct disorders and child abuse. Behind this background, we tested the main hypothesis of our study; that Dialectical Behavioral Therapy for Adolescents is an effective treatment for these patients. Methods Dialectical Behavioral Therapy (DBT) has been developed by Marsha Linehan - especially for the outpatient treatment of chronically non-suicidal patients diagnosed with borderline personality disorder. The modified version of DBT for Adolescents (DBT-A) from Rathus & Miller has been adapted for a 16-24 week outpatient treatment in the German-speaking area by our group. The efficacy of treatment was measured by a pre-/post- comparison and a one-year follow-up with the aid of standardized instruments (SCL-90-R, CBCL, YSR, ILC, CGI). Results In the pilot study, 12 adolescents were treated. At the beginning of therapy, 83% of patients fulfilled five or more DSM-IV criteria for borderline personality disorder. From the beginning of therapy to one year after its end, the mean value of these diagnostic criteria decreased significantly from 5.8 to 2.75. 75% of patients were kept in therapy. For the behavioral domains according to the SCL-90-R and YSR, we have found effect sizes between 0.54 and 2.14. During treatment, non-suicidal self-injurious behavior reduced significantly. Before the start of therapy, 8 of 12 patients had attempted suicide at least once. There were neither suicidal attempts during treatment with DBT-A nor at the one-year follow-up. Conclusions The promising results suggest that the interventions were well accepted by the patients and their families, and were associated with improvement in multiple domains including suicidality, non-suicidal self-injurious behavior, emotion dysregulation and depression from the beginning of therapy to the one-year follow-up.

While several recent evaluation studies have shown the efficacy of parent training programs for children with neurodevelopmental disorders, manual-based training in German is still scarce. To address this gap, we developed a specific modularized training program for parents of children from preschool to pre-adolescent age with Autism Spectrum Disorder (FETASS). The overarching purpose of the FETASS intervention is to enhance social communication behavior and quality of life of the child by coaching parents. As a proximal target, the FETASS training aims to provide families with behavior management and communication strategies. The development of the training was influenced by published behavioral parent trainings and autism-specific interventions. The training comprises eight weekly sessions and targets families whose children have a diagnosis of Autism Spectrum Disorder (ASD) without intellectual and language impairments. As a preliminary pilot study, the purpose was to evaluate the acceptability of the training. Furthermore, the study aimed at initially evaluating social communication behavior, quality of life of the child, parental stress level, and parenting after training in comparison to a treatment as usual (TAU) group. Exploratively, long-term effects were investigated after 6 months of training as well. In total, 57 families participated (n [TAU] = 29, n [FETASS] = 28). Questionnaires about social communication behavior and quality of life of the child, parental stress, and parenting were administered at three time points (t1: baseline TAU/FETASS, t2: post TAU/FETASS; and t3: 6-month follow-up after FETASS). Primary outcome measures were the social communication behavior of the child and the parent's proxy report on quality of life of the child. Secondary outcome measures were changes in parental stress and parenting behavior. Acceptability of the training was very high and we had almost no dropouts during training. Results for the primary outcome measure of social communication behavior, overall quality of life of the child, and long-term effects on social communication behavior were not significant. While long-term findings for parent stress reduction and for the quality of life of the child are promising, further research has to be done in a future randomized controlled trial. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) represent two common neurodevelopmental disorders with considerable co-occurrence. Their comorbidity (ASD + ADHD) has been included in the latest diagnostic guidelines (DSM-V, 2013). The present study focuses on social visual attention that i) is a main aspect of social attention reflecting social cognition and ii) its atypicalities have been suggested as a potential biomarker for ASD. Considering the possible shared background of both disorders and their comorbidity, it is important to compare such traits directly. Here, 73 children and adolescents paired for age and IQ diagnosed with ASD (N = 12), ADHD (N = 21), comorbid ASD + ADHD (N = 15), and "typically developing" (TD) controls (N = 25), were shown static real-life social scenes while their gaze movements were recorded with eye-tracking. Scenes with two levels of social complexity were presented: low complexity (one person depicted) and high (four interacting individuals). Gaze fixation variables were investigated. Fixation duration on faces was significantly reduced only in ASD + ADHD which also required longer time to fixate all faces at least once. Fixation duration on faces in ASD was reduced, compared to TD, only when looking at scenes with high versus low social complexity. ADHD individuals did not differ from TD. Concluding, the observed alterations of social visual attention support the existence of possible dysfunctional particularities differentiating ASD, ADHD, and ASD + ADHD, which can be revealed with the new method of eye-tracking technique. The objective gaze measurements provided contribute to the development of biomarkers enabling early diagnosis, amelioration of care and further interventions specified for each group. [ABSTRACT FROM AUTHOR]

Social interaction in individuals with Autism Spectrum Disorder (ASD) is characterized by qualitative impairments that highly impact quality of life. Bayesian theories in ASD frame an understanding of underlying mechanisms suggesting atypicalities in the evaluation of probabilistic links within the perceptual environment of the affected individual. To address these theories, the present study explores the applicability of an innovative Bayesian framework on social visual perception in ASD and demonstrates the use of gaze transitions between different parts of social scenes. We applied advanced analyses with Bayesian Hidden Markov Modeling (BHMM) to track gaze movements while presenting real-life scenes to typically developing (TD) children and adolescents (N = 25) and participants with ASD and Attention-Deficit/Hyperactivity Disorder (ASD+ADHD, N = 15) and ASD without comorbidity (ASD, N = 12). Regions of interest (ROIs) were generated by BHMM based both on spatial and temporal gaze behavior. Social visual perception was compared between groups using transition and fixation variables for social (faces, bodies) and non-social ROIs. Transition variables between faces, namely gaze transitions between faces and likelihood of linking faces, were reduced in the ASD+ADHD compared to TD participants. Fixation count to faces was also reduced in this group. The ASD group showed similar performance to TD in the studied variables. There was no difference between groups for non-social ROIs. Our study provides an innovative, interpretable example of applying Bayesian theories of social visual perception in ASD. BHMM analyses and gaze transitions have the potential to reveal fundamental social perception components in ASD, contributing thus to amelioration of social-skill interventions. [ABSTRACT FROM AUTHOR]

Objectives: The influence of food intake on behavioural disorders was already described in the early 20th century. Elimination of individually allergenic food items from individual diets ["oligoantigenic diet" (OD)] showed promise to improve attention-deficit/hyperactivity disorder (ADHD) symptoms. However, only few of the positive results were evaluated by blinded symptom rating. Therefore the present study's purpose was to evaluate the reliability of a non-blinded rating of the ADHD Rating Scale IV (ARS) for the assessment of OD effects in comparison to a blinded rating of the ARS based on pseudonymized video recordings. Methods: Ten children (8m/2f) aged 8 to 14 with ADHD according to ICD-10 participated in an uncontrolled, open-label dietary intervention study. Food items, commonly related to intolerances, were eliminated for four weeks. Participants with > 40% improvement in the ARS between T1 (before the diet) and T2 (after the diet) were defined as responders. Nutrients with individual relevance to ADHD symptoms were identified in a following reintroduction phase (T3–T4) lasting 8–16 weeks. The ARS was completed by a non-blinded child and adolescent psychiatrist (T0-T4). Sessions were recorded on video, pseudonymized, and evaluated by three blinded raters. Complete data were captured for eight children. The inter-rater reliability between the non-blinded therapist and every blinded rater was determined by the intra-class correlation coefficient (ICC). Correlations according to Pearson and Spearman between the non-blinded and blinded rating were calculated for each rater. Results: Two blinded raters and the non-blinded rater considered 5 of 8 (62.5%) children as responders, whereas one blinded rater disagreed as to the success of one case thus considering only 4 of 8 children as responders to the diet. Inter-rater reliability was assessed after each rater having scored 33 videos: The intra-class coefficients were >.9 for all raters (rater 1: ICC =.997, rater 2: ICC =.996, rater 3: ICC =.996) and the Spearman rho between the raters were high (n =33; rater 1: rho =.989, p <.0001, rater 2: rho =.987, p <.0001, rater 3: rho =.984, p <.0001), respectively. Discussion: As both, blinded and non-blinded ratings of the ARS, revealed relevant significant improvement of ADHD scores in children following an OD in this uncontrolled trial, Randomized controlled trials appear as highly desirable in order to replicate these improvements and to establish reliable and unbiased effect sizes thereby fostering further more objective confirmatory measurements. [ABSTRACT FROM AUTHOR]

Objective: Relationships between sleep, screen-based media, and ADHD symptomatology were investigated using a case- and community-based approach. Method : N = 357 healthy and N = 61 children with ADHD (12.72 ± 2.83 years) completed a sleep and media questionnaire. To measure ADHD symptomatology, parents filled out the Strengths and Weaknesses of ADHD symptoms and Normal behavior (SWAN) scale. Two samples were formed: a matched (N = 61 patients and N = 61 controls) and a community sample (N = 357 healthy participants and N = 20 patients). Results : Compared with controls, participants with ADHD reported delayed sleep onset and more screen time on school days. Adolescent patients showed more behavior promoting delayed sleep phase. In the community sample, media time, sleep deviation, and circadian rhythm were correlated with ADHD symptomatology. Furthermore, media time, sleep-wake behavior, and sleep deviation were predictive of ADHD symptomatology (variance explained = 4%-15%). Conclusion : Longer media time and inadequate sleep-wake behavior increase the risk of ADHD-like symptoms. However, research using objective assessments is needed to disentangle this distinct association and to provide possible directions for intervention. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Recent preliminary studies indicated a seasonal association of BMI at admission to inpatient treatment for anorexia nervosa (AN), indicating lower BMI in the cold season for restrictive AN. An impaired thermoregulation was proposed as the causal factor, based on findings in animal models of AN. However, findings regarding seasonality of BMI and physical activity levels in the general population indicate lower BMI and higher physical activity in summer than in winter. Therefore, we aimed to thoroughly replicate the findings regarding seasonality of BMI at admission in patients with AN in this study. Method: AN subtype, age- and gender-standardized BMI scores (BMI-SDS) at admission, mean daily sunshine duration and ambient temperature at the residency of 304 adolescent inpatients with AN of the multi-center German AN registry were analyzed. Results: A main effect of DSM-5 AN subtype was found (F(2,298) = 6.630, p = .002), indicating differences in BMI-SDS at admission between restrictive, binge/purge and subclinical AN. No main effect of season on BMI-SDS at admission was found (F(1,298) = 4.723, p = .025), but an interaction effect of DSM-5 subtype and season was obtained (F(2,298) = 6.625, p = .001). Post-hoc group analyses revealed a lower BMI-SDS in the warm season for restrictive AN with a non-significant small effect size (t(203.16) = 2.140, p = .033; Hedges′g = 0.28). Small correlations of mean ambient temperature (r = −.16) and daily sunshine duration (r = −.22) with BMI-SDS in restrictive AN were found. However, the data were widely scattered. Conclusions: Our findings are contrary to previous studies and question the thermoregulatory hypothesis, indicating that seasonality in AN is more complex and might be subject to other biological or psychological factors, for example physical activity or body dissatisfaction. Our results indicate only a small clinical relevance of seasonal associations of BMI-SDS merely at admission. Longitudinal studies investigating within-subject seasonal changes might be more promising to assess seasonality in AN and of higher clinical relevance. [ABSTRACT FROM AUTHOR]