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Zusammenfassung. Genetische Varianten beeinflussen die Gewichtsregulation und die Entwicklung von Essstörungen. Zunächst haben familienbasierte, sogenannte formalgenetische Studien den erblichen Anteil an der Gewichtsregulation und an der Ätiologie von Essstörungen beleuchtet. In einer Vielzahl von Studien zeigten sich sowohl für die Varianz des Körpergewichts als auch für die Entstehung von Essstörungen Erblichkeitsschätzer (Heritabilitätsraten) von über 50 %. Mit diesem Wissen begab man sich in den 90er-Jahren des letzten Jahrhunderts auf die Suche nach den zugrundeliegenden Genen (genauer: genetischen Varianten), die das Körpergewicht, das Essverhalten oder beide Phänotypen auf Grundlage geteilter Mechanismen beeinflussen. Zunächst wurden Kandidatengenstudien durchgeführt. Dabei untersuchte man auf Grundlage unterschiedlicher, v. a. aber pathophysiologisch plausibler Überlegungen Gene mit hoher Relevanz für die untersuchten Phänotypen. Dieser Ansatz war für Essstörungen nicht sehr erfolgreich, für die Gewichtsregulation konnte eine Handvoll Gene identifiziert werden. Verbunden mit großen methodischen Fortschritten in der genetischen Forschung und v. a. der Etablierung sogenannter genomweiter Assoziationsstudien (GWAS) Anfang der 2000er-Jahre konnten bislang über 1000 Varianten/Genorte detektiert werden, die das Körpergewicht beeinflussen. Für die Essstörung Anorexia nervosa (AN) sind aktuell acht solcher Genorte beschrieben. Diese Ergebnisse, aber auch aktuelle Ansätze zu phänotypübergreifenden Analysen lassen Einblicke in die komplexe Regulation des Körpergewichtes zu und haben zudem unerwartete Pathomechanismen für AN aufgezeigt.

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

OBJECTIVE The study was undertaken to determine the prevalence of subclinical and overt thyroid dysfunction as well as thyroid autoimmunity in depressed adolescents in comparison to the general pediatric population. Additionally, the relationship between parameters of thyroid function and Beck Depression Inventory-II (BDI-II) scores was examined. METHODS Parameters of thyroid function (thyrotropin, free thyroxine, thyroid peroxidase antibodies) and prevalence of thyroid dysfunction and autoimmunity were determined in 360 adolescents (11-19 years) with at least mild depression (BDI-II score > 13) between June 2016 and December 2019 and in a representative reference cohort without evidence of impaired mental health from a nationwide survey (German Health Interview and Examination Survey for Children and Adolescents [KiGGS], 2003-2006). RESULTS There was a higher prevalence of thyroid peroxidase antibody positivity in depressed adolescents (mean ± SD BDI-II, 30.0 ± 10.4) compared to KiGGS participants (depressed adolescents: 5.8%, 95% CI [3.7-8.6]; odds ratio [OR] 1.9, P = .009, d = 0.36; KiGGS participants: 3.1%, 95% CI [2.5-3.9]). The prevalence of subclinical hypothyroidism was likewise higher in depressed adolescents (9.1%, 95% CI [6.3-12.4] vs KiGGS participants: 2.1%, 95% CI [1.6-2.7]; OR 4.7, P

OBJECTIVE The aim of this study was to investigate the frequency of newly diagnosed type 1 diabetes without evidence of autoimmunity and the respective frequencies of ketoacidosis in children, adolescents, and young adults during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with the previous decade. RESEARCH DESIGN AND METHODS Based on data from the German Diabetes Prospective Follow-up Registry (DPV), we compared data from 715 children, adolescents, and young adults, newly diagnosed with type 1 diabetes during the COVID-19 pandemic in Germany between 1 March and 30 June 2020, with data from 5,428 children, adolescents, and young adults of the same periods from 2011 to 2019. Adjusted differences and relative risks (RRs) of negative β-cell autoantibody test results and diabetic ketoacidosis were estimated using multivariable log-binomial regression analysis. An upper noninferiority test (margin 1%) was applied to evaluate whether the autoantibody-negativity rate in 2020 was not higher than that in 2011 to 2019. RESULTS The estimated frequencies of autoantibody negativity in 2020 and 2011–2019 were 6.6% (95% CI 5.1–8.4) and 7.2% (95% CI 6.5–8.0), respectively, with an absolute difference of −0.68% (90% CI −2.07 to 0.71; Pupper noninferiority = 0.023). The increase of the estimated frequency of diabetic ketoacidosis during the COVID-19 pandemic was similar between autoantibody-negative and -positive type 1 diabetes (adjusted RRs 1.28 [95% CI 0.80–2.05] and 1.57 [1.41–1.75], respectively). CONCLUSIONS This study found no evidence that the COVID-19 pandemic leads to a significantly increased number of new cases with autoantibody-negative type 1 diabetes in children, adolescents, and young adults. In addition, autoantibody-negative type 1 diabetes showed no particular susceptibility to ketoacidosis, neither before nor during the pandemic.

Objective To examine the effect of intrathecal application of nusinersen on the respiratory function in terms of vital capacity in pediatric patients with spinal muscular atrophy (SMA). SMA is characterized by on-going muscular atrophy and weakness that lead to respiratory insufficiency. In recent years therapy with nusinersen has been shown to improve motor function in patients with SMA. Methods We retrospectively analyzed data from 12 pediatric patients (aged 4–12 years) with SMA II or III (7 walkers, 5 sitters) treated with nusinersen. We examined forced vital capacity (FVC) at baseline (i.e., before treatment) and 180 and 300 days after initiation of treatment. Results No significant difference in the ranks of FVC of patients with SMA at baseline and day 300 was found and, thus, stable FVCs are implied (n = 6; Z = - 0.105, pexact = 1.000; Medianbaseline = 96.0%, 95%-CI [86.5, 110.5]; Medianday300 = 96.0%, 95%-CI [92.0, 109.5]; s. Table 1). This also applied to the comparison between baseline and day 180 (n = 7; Z = 0.00, pexact = 1.00; Medianbaseline = 93.0%, 95%-CI [85.0, 110.0]; Medianday180 = 91.0%, 95%-CI [72.0, 118.0]) and day 180 and 300 (n = 9; Z = - 0.533, pexact = .652; Medianday180 = 95.0%, 95%-CI [72.0, 118.0]; Medianday300 = 90.0%, 95%-CI [74.0, 105.0]). Conclusion Nusinersen therapy alone may not improve lung function of pediatric patients with SMA type II or III.

While there is a growing body of evidence regarding the behavioral and neurofunctional changes in response to the longitudinal delivery of transcranial direct current stimulation (tDCS), there is limited evidence regarding its structural effects. Therefore, the present study was intended to investigate the effect of repeatedly applied anodal tDCS over the primary somatosensory cortex on the gray matter (GM) and white matter (WM) compartment of the brain. Structural tDCS effects were, moreover, related to effects evidenced by functional imaging and behavioral assessment. tDCS was applied over the course of 5 days in 25 subjects with concomitant assessment of tactile acuity of the right and left index finger as well as imaging at baseline, after the last delivery of tDCS and at follow-up 4 weeks thereafter. Irrespective of the stimulation condition (anodal vs. sham), voxel-based morphometry revealed a behaviorally relevant decrease of GM in the precuneus co-localized with a functional change of its activity. Moreover, there was a decrease in GM of the bilateral lingual gyrus and the right cerebellum. Diffusion tensor imaging analysis showed an increase of fractional anisotropy exclusively in the tDCSanodal condition in the left frontal cortex affecting the final stretch of a somatosensory decision making network comprising the middle and superior frontal gyrus as well as regions adjacent to the genu of the corpus callosum. Thus, this is the first study in humans to identify structural plasticity in the GM compartment and tDCS-specific changes in the WM compartment in response to somatosensory learning.

Transfer learning is an immanent feature of perceptual learning. Yet, despite the increasingly widespread application of transcranial direct current stimulation (tDCS) to study learning, transfer effects in response to tDCS have not been studied. Therefore, the present study investigated the transfer of tactile acuity evoked by repeatedly applied anodal tDCS over the left primary somatosensory cortex (S1) over the course of five days from the dominant (right) to the non-dominant (left) index finger (IF). There was a complete transfer of improvement of the right IF to its contralateral homologue by follow-up four weeks later. Changes in tactile acuity of the left IF in the tDCSanodal condition were accompanied by a significant longitudinal change in functional connectivity between the left S1 and the right secondary somatosensory cortex (S2) assessed at day five of tDCS delivery and four week later. Moreover, we observed a close link between tactile acuity and (changes of) functional connectivity of the right S2 in the tDCSanodal condition identifying the S2 as neural correlate to mediate the transfer of tDCS effects in the somatosensory domain. These findings provide unprecedented evidence of transfer effects evoked by tDCS, implicate the S2 in somatosensory transfer learning and provide evidence in support of models of perceptual learning allocating learning to the reweighting of connections between different levels of processing.