Using artificial intelligence-based technologies to detect clinically relevant changes of gross motor function in children with cerebral palsy.

AIM: To compare the 66-item Gross Motor Function Measure (GMFM-66) with the reduced version of the GMFM-66 (rGMFM-66) with respect to the detection of clinically relevant changes in gross motor function in children with cerebral palsy (CP). METHOD: The study was a retrospective single centre analysis of children with CP who participated in a rehabilitation programme. Overall, 1352 pairs of GMFM-66 and rGMFM66 measurements with a time interval of 5 to 7 months were available. To measure clinically relevant changes in gross motor function, the individual effect size (iES) was calculated. RESULTS: The study population consisted of 1352 children (539 females), mean age 6 years 4 months (SD 2 years 4 months). The iES based on the GMFM-66 and the rGMFM-66 showed a significant correlation (r = 0.84, p < 0.001). The analysis of the area under the receiver operating characteristic curve showed an excellent agreement for clinically relevant gross motor improvement (Cohen's d ≥ 0.5; area under the curve = 0.90 [95% confidence interval 0.88-0.92]) or deterioration (Cohen's d ≤ -0.5; area under the curve = 0.95 [95% confidence interval 0.92-0.97]). INTERPRETATION: Performing the rGMFM-66 saves time compared to the full GMFM-66. The rGMFM-66 showed good agreement with the GMFM-66 with respect to the detection of clinically relevant changes in gross motor function in children with CP, so its use in everyday clinical practice seems justifiable. WHAT THIS PAPER ADDS: The reduced version of the 66-item Gross Motor Function Measure (rGMFM-66) detects clinically relevant changes in gross motor function in children with cerebral palsy. The rGMFM-66 correlates highly with the full GMFM-66. The rGMFM-66 can be used in clinical practice when the time schedule is limited.

Validation of the maximal cardiopulmonary exercise test in adolescents with major depressive disorder and comparison of cardiorespiratory fitness with sex- and age-related control values.

Endurance training has been shown to be effective in treating adolescents with major depressive disorder (MDD). To integrate endurance training into the therapeutic setting and the adolescents' daily lives, the current performance status of the adolescents should be accurately assessed. This study aims to examine adolescents with MDD concerning exhaustion criteria during a cardiopulmonary exercise test (CPET), as well as to compare the values obtained thereon with sex- and age-related control values. The study included a retrospective examination of exhaustion criteria ((i) oxygen consumption (V̇O2) plateau, (ii) peak respiratory exchange ratio (RERpeak) > 1.0, (iii) peak heart rate (HRpeak) ≥ 95% of the age-predicted maximal HR, and (iv) peak blood lactate concentration (BLCpeak) > 8.0 mmol⋅L-1) during a graded CPET on a cycle ergometer in adolescents with MDD (n = 57). Subsequently, maximal V̇O2, peak minute ventilation, V̇O2 at the first ventilatory threshold, and peak work rate of participants who met at least two of four criteria were compared with published control values using an independent-sample t-test. Thirty-three percent of the total population achieved a V̇O2 plateau and 75% a RERpeak > 1.0. The HR and BLC criteria were met by 19% and 22%, respectively. T-test results revealed significant differences between adolescents with MDD and control values for all outcomes. Adolescents with MDD achieved between 56% and 83% of control values.   Conclusions: The study shows that compared with control values, fewer adolescents with MDD achieve the exhaustion criteria on a CPET and adolescents with MDD have significantly lower cardiorespiratory fitness.   Clinical trial registration: No. U1111-1145-1854. What is Known: • It is already known that endurance training has a positive effect on depressive symptoms. What is New: • A relevant proportion of adolescents with major depressive disorder do not achieve their V̇O2max during a graded cardiopulmonary exercise test. • Adolescents with major depressive disorder have significantly lower cardiorespiratory fitness compared to sex- and age-related control values.

Pharmacological anti-inflammatory treatment in children and adolescents with depressive symptoms: A systematic-review and meta-analysis.

Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).

[Movement as a Neuromodulator: How Physical Activity Influences the Physiology of Adolescent Depression]. / Bewegung als Neuromodulator: Wie körperliche Aktivität die Physiologie der adoleszenten Depression reguliert.

Movement as a Neuromodulator: How Physical Activity Influences the Physiology of Adolescent Depression Abstract: In the context of adolescent depression, physical activity is becoming increasingly recognized for its positive effects on neuropathology. Current scientific findings indicate that physical training affects the biological effects of depression during adolescence. Yet the pathophysiology of adolescent depression is not yet fully understood. Besides psychosocial and genetic influences, various neurobiological factors are being discussed. One explanation model describes a dysfunction of the hypothalamus-pituitary-adrenal axis (HPA axis) with a sustained elevation in cortisol concentration. Recent studies highlight neuroimmunological processes and a reduced concentration of growth factors as causative factors. These changes appear to lead to a dysregulation of the excitation and inhibition balance of the cerebral cortex as well as to cerebral morphological alterations. Regular physical training can potentially counteract the dysregulation of the HPA axis and normalize cortisol levels. The release of proinflammatory cytokines is inhibited, and the expression of growth factors involved in adult neurogenesis is stimulated. One should ensure the synergistic interaction of biological and psychosocial factors when designing the exercise schedule (endurance or strength training, group or individual sports, frequency, duration, and intensity). Addressing these open questions is essential when integrating physical activity into the guidelines for treating depressive disorders in children and adolescents.

Contingent negative variation to tactile stimuli - differences in anticipatory and preparatory processes between participants with and without blindness.

People who are blind demonstrate remarkable abilities within the spared senses and compensatory enhancement of cognitive skills, underscored by substantial plastic reorganization in relevant neural areas. However, little is known about whether people with blindness form top-down models of the world on short timescales more efficiently to guide goal-oriented behavior. This electroencephalography study investigates this hypothesis at the neurophysiological level, focusing on contingent negative variation (CNV) as a marker of anticipatory and preparatory processes prior to expected events. In sum, 20 participants with blindness and 27 sighted participants completed a classic CNV task and a memory CNV task, both containing tactile stimuli to exploit the expertise of the former group. Although the reaction times in the classic CNV task did not differ between groups, participants who are blind reached higher performance rates in the memory task. This superior performance co-occurred with a distinct neurophysiological profile, relative to controls: greater late CNV amplitudes over central areas, suggesting enhanced stimulus expectancy and motor preparation prior to key events. Controls, in contrast, recruited more frontal sites, consistent with inefficient sensory-aligned control. We conclude that in more demanding cognitive contexts exploiting the spared senses, people with blindness efficiently generate task-relevant internal models to facilitate behavior.

Personality Disorder in Adolescent Patients with Anorexia Nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a highly debilitating disease which frequently results in chronification and often originates in adolescence. Personality traits have been associated with the onset and maintenance of AN; moreover, study results indicated a worse treatment outcome in patients with AN and comorbid personality disorder (PD). However, research on PD in adolescent AN is scarce. METHODS: The sample consists of 73 female adolescent patients with AN. We investigated comorbid PD and AN symptom severity performing the International Personality Disorder Examination (IPDE) and the Eating Disorder Inventory 2 (EDI-2). RESULTS: Almost a third (27.4%) of all participants were diagnosed with comorbid PD. They had significantly higher EDI-2 total scores reflecting overall stronger symptom severity, as well as significantly higher scores in the subscales "ineffectiveness," "interpersonal distrust," "interoceptive awareness," "asceticism," "impulse regulation," and "social insecurity." CONCLUSION: PD is an important and frequent comorbid condition in adolescent AN and should be addressed in diagnostic and treatment planning. Early diagnosis of comorbidity could have an impact on choosing specialized treatment for adolescents with AN and PD in order to enhance the outcome.

How Stressful Is Examining Children with Symptoms of Child Abuse?-Measurement of Stress Appraisal (SAM) in German Physicians with Key Expertise in Pediatrics.

BACKGROUND: Pediatricians frequently feel uncertain about their ability to detect early symptoms of child abuse and how to respond in suspected cases. AIM: This study investigated the transactional stress model in German pediatricians who experienced imagination stories with a child protection scenario and another potentially stress-triggering scenario. METHODS: A two-part survey was conducted online. Each part included a different imagination story and evaluation of the Stress Appraisal Measure (SAM), as well as questions on child protection, current problematics, and suggested remedies. In total, 96 pediatricians participated. The child abuse scenario was perceived as significantly more threatening and more stressful than a medical emergency. The pediatricians declared moderate familiarity with the Child Protection Guidelines and the Federal Child Protection Act and an average confidence in their application. The greatest perceived problems were communication difficulties with parents and youth welfare services. Suggested improvements were concrete procedural directives, more training programs, better interdisciplinary networks, and greater exchange among colleagues. CONCLUSIONS: To optimize their potential in the child protection system, pediatricians need to be better supported in coping with the identified stressors in child abuse scenarios.

Changes in the TMS-evoked potential N100 in the dorsolateral prefrontal cortex as a function of depression severity in adolescents.

Studies using transcranial magnetic stimulation with simultaneous electroencephalography (TMS-EEG) revealed an imbalance between cortical excitation and inhibition (E/I) in the dorsolateral prefrontal cortex (DLPFC) in depression. As adolescence is a developmental period with an increase in depression prevalence and profound neural changes, it is crucial to study the relationship between depression and cortical excitability in adolescence. We aimed to investigate the cortical excitability of the DLPFC in adolescents with depression and a dependency of the TMS-evoked potential N100 on the depression severity. 36 clinical patients (12-18 years of age; 21 females) with a major depressive episode were assessed twice in a longitudinal design: shortly after admission (T0) and after six weeks of intervention (T1). GABA-B-mediated cortical inhibition in the left and right DLPFC, as assessed by the N100, was recorded with EEG. Significantly higher depression scores were reported at T0 compared to T1 (p < 0.001). N100 amplitudes were significantly increased (i.e., more negative) at T0 compared to T1 (p = 0.03). No significant hemispheric difference was found in the N100 component. The correlation between the difference in depression severity and the difference in N100 amplitudes (T0-T1) obtained during stimulation of the left DLPFC did not remain significant after correction for testing in both hemispheres. Higher N100 amplitudes during a state of greater depression severity are suggestive of an E/I imbalance in the DLPFC in adolescents with an acute depressive episode. The N100 reduction potentially reflects a normalization of DLPFC over inhibition in association with decreased depressive symptomatology, indicating severity dependency.

Diagnostic Evaluation of the Functional Muscle-Bone Unit in Children With Cerebral Palsy With and Without Low Trauma Fractures.

Children and adolescents with cerebral palsy (CP) are at increased risk of low trauma fractures (LTF) due to low bone mineral content (BMC). The risk of LTFs might be overestimated by only age - and sex adjusted Z-scores for BMC because Z-score based DXA techniques do not take into account other relevant parameters like height, muscle and fat mass. This study aimed to present an update of the functional muscle-bone unit-algorithm (uFMBU-A) to evaluate bone health in children with CP in order to predict the risk of LTF taking into account the parameters sex, age, height, muscle and fat mass. We performed a monocentric retrospective analysis of 177 DXA-scans of children and adolescents with CP aged 8-19. Six of these 177 patients had sustained at least 1 LTF. Age-, sex- and size adjusted Z-scores of total body less head (TBLH)-BMC, lean body mass and fat mass were calculated. The uFMBU-A was applied to the study group and results were compared with established Z-score based DXA-measurements and algorithm based diagnostic techniques concerning the prediction of LTF risk. The uFMBU-A had the greatest diagnostic odds ratio (13.3 [95% CI 2.41; 72.9]) of the evaluated predictors with a sensitivity of 50.0% (95% CI 11.8; 88.2), specifity of 93% (95% CI 88.1; 96.3). The uFMBU-A was the most accurate method of the evaluated parameters to predict LTF in children with CP and is recommended when evaluating bone health.

Reference centiles of bone mineral density, and body composition of lower limbs in children and adolescents for Hologic DXA Discovery model A.

Background: Regional Dual-energy X-ray absorptiometry (DXA) assessments are useful for patients where whole body measurements are not feasible due to positioning difficulties because of anatomic anomalies (e.g. severe scoliosis) and artifacts due to neuroorthopedic hardware. Until now, there is a lack of reference centiles of bone mineral density and body composition of lower limbs for the DXA device Hologic Discovery model A densitometer. The study aimed to generate age-and sex specific reference centiles of bone mineral content (BMC), bone mineral density (BMD), lean body mass (LBM), and fat mass (FM) of the lower limbs of children and adolescents of Hologic DXA system (Discovery model A). Methodology: Data from children and adolescents aged 8-20 years of the National Health and Nutrition Examination Survey (NHANES) of the years 2015-2018 were used to create age-specific and sex-specific reference centiles. Study population was subdivided into three ethnic groups (non-Hispanic Black, non-Hispanic White and Mexican-American). The LMS method was used to calculate the reference centiles. Study population was adjusted concerning the BMI. Results: A total of DXA scans of 769 non-Hispanic Black children (386 females), 937 non-Hispanic White children (447 females) and 692 Mexican-American children (370 females) were used to calculate age-specific and sex-specific reference curves. 881 DXA scans had to be excluded because of extreme BMI values of the study population, leaving 513 non-Hispanic Black (205 females), 346 Mexican-American children (179 females), 658 Non-Hispanic White (282 females) for statistical analysis and creating age-and sex specific reference centiles after BMI adjustment. Conclusions: We presented pediatric reference centiles for regional bone mineral density, bone mineral content, lean body mass and fat mass of the lower limbs which were age-and sex-specific for three ethnic groups (Mexican-American, non-Hispanic Black and non-Hispanic-White). The reference centiles can be used for the Hologic DXA system Discovery model A with the software version 3.2.

Interaction between fat- and muscle development in children and adolescents.

Background: Prevalence of obesity increased noticeably during the last decades. Little is known so far about the association between fat accumulation due to obesity and skeletal muscle mass. The aim of this study was to describe the association between fat mass and muscle mass after adjusting for relevant confounding factors in the National Health and Nutrition Examination Survey (NHANES) study population of children and adolescents. We postulated a negative correlation between fat mass and lean body mass. Methodology: A total of 849 whole body DXA-scans of the NHANES study population of children and adolescents aged eight to twenty years of the years 1999-2004 were eligible for statistical analysis. Appendicular lean body mass (appLBM) was used to evaluate muscle mass. Bivariate analysis (Pearson's correlation coefficient), multiple linear regression analysis and mediation analysis were performed. The multiple regression analysis and mediation analysis were adjusted for weight, age height, sex ethnicity and physical activity. Results: Fat mass correlates with appendicular lean body mass (Pearons's r 0.336, p < 0.001). In the multiple linear regression analysis the regression coefficient between appLBM and FM was positive (0.204; p < 0.001), when considering appendicular lean body mass, fat mass and body weight, the regression coefficient was negative (-0.517; p < 0.001). Conclusions: Study results indicate a negative association of fat mass and skeletal muscle mass in children and adolescents, when weight, age, height, sex ethnicity and physical activity are considered. Further investigations are needed to evaluate if there is a biochemical interaction between fat cells and muscle cells that could explain this effect.

Influence of motivational placebo-related factors on the effects of exercise treatment in depressive adolescents.

Recent meta-analyses reveal a moderate effect of physical activity (PA) in the treatment of adolescent depression. However, not only the underlying neurobiological mechanisms, also the influences of placebo-related motivational factors (beliefs and expectancies in sporting, enjoyment and prior sports experiences), are still unclear. Based on the data of our prior study "Mood Vibes", we hypothesized that placebo-inherent factors like positive prior sports experiences and motivational factors, (positive beliefs, expectancies, and enjoyment related to PA), would increase the effects of an add-on exercise-therapy in juvenile depression. From 64 included depressed adolescents, 41 underwent an intensive add-on PA-therapy. Motivational factors were assessed using sport-specific scales. The changes in depression scores under treatment were rated by self-rating scale (German "Childhood Depression Inventory", (DIKJ)). A mixed model for repeated measures (MMRM) was used to analyze the effects of the different motivational variates on DIKJ. While prior sports experiences had no impact, motivational factors showed a significant effect on PA-induced changes in DIKJ scores (p = 0.002). The demotivated participants improved less, whereas it was sufficient to be neutral towards sporting to benefit significantly more. Motivational placebo-related factors (beliefs, expectancies and enjoyment regarding PA) affected the outcomes of an exercise treatment in depressed adolescents. Yet, a neutral mindset was sufficient to profit more from PA. Prior sporting in the sense of positive conditioning and as a protective factor did not play a role. Knowledge about these influences could in a second step help to develop tailored therapies.

Artificial intelligence to improve efficiency of administration of gross motor function assessment in children with cerebral palsy.

AIM: To create a reduced version of the 66-item Gross Motor Function Measure (rGMFM-66) using innovative artificial intelligence methods to improve efficiency of administration of the GMFM-66. METHOD: This study was undertaken using information from an existing data set of children with cerebral palsy participating in a rehabilitation programme. Different self-learning approaches (random forest, support vector machine [SVM], and artificial neural network) were evaluated to estimate the GMFM-66 score with the fewest possible test items. Test agreements were evaluated (among other statistics) by intraclass correlation coefficients (ICCs). RESULTS: Overall, 1217 GMFM-66 assessments (509 females, mean age 8y 10mo [SD 3y 9mo]) at a single time and 187 GMFM-66 assessments and reassessments (80 females, mean age 8y 5mo [SD 3y 10mo]) after 1 year were evaluated. The model with SVM predicted the GMFM-66 scores most accurately. The ICCs of the rGMFM-66 and the full GMFM-66 were 0.997 (95% confidence interval [CI] 0.996-0.997) at a single time and 0.993 (95% CI 0.993-0.995) for the evaluation of the change over time. INTERPRETATION: The study shows that the efficiency of the full GMFM-66 assessment can be increased by using machine learning (self-learning algorithms). The presented rGMFM-66 score showed an excellent agreement with the full GMFM-66 score when applied to a single assessment and when evaluating the change over time.

Differential effects of ergometer-cycling and Whole-Body-Vibration training on serological BDNF and IGF-1 in the treatment of adolescent depression - is there an impact of BDNFp.Val66Met variants?

BACKGROUND: Pathogenesis and treatment of adolescent depression may be influenced by growth-factors, including brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). We investigated, if treatment response to two different add-on exercise-therapies in juvenile depression, differ in the changes of BDNF and IGF-1 serology. A subgroup analysis for genetic variations in BDNF p.Val66Met-variants was added. METHODS: Included subjects in the study (N = 64), aged 13 to 17 years, were diagnosed with major depression, controls received inpatient treatment as usual (TAU). Intervention groups performed as add-on to TAU two different forms of exercise-therapy: endurance ergometer cycling (EC) and muscle strengthening whole body vibration (WBV). We expected both exercise-forms to increase BDNF and IGF-1 serology and by this pathway to improve depression scores significantly stronger than the control group. RESULTS: None of the experimental groups showed significant changes in BDNF between measurement time points. However, after 6 weeks exercise, BDNF of both intervention groups were significantly higher compared to TAU,. The IGF-1 increase after 6 weeks intervention was significant for EC only. No correlations of BDNF and IGF-1 to depression scores were found. Group analysis in BDNF p.Val66Met variants showed a trend for better response in depression scores to exercise-treatment for the Val66Val group. LIMITATIONS: A small sample size, the non-randomized controls and the neglect of psychosocial factors have to be considered as limitations. CONCLUSIONS: Endurance and muscle strengthening trainings seem to influence serological BDNF and IGF-1 differentially. However, the changes in growth factors did not correlate to the decreases in depression scores. BDNF p.Val66Val variant seems to be more receptive for exercise treatment. Identifying biomarkers (growth factors, genetic variants) in adolescent depression could help to develop tailored treatment strategies.

Immunological Effects of an Add-On Physical Exercise Therapy in Depressed Adolescents and Its Interplay with Depression Severity.

BACKGROUND: Pro-inflammatory cytokines (PICs) have gained attention in the pathophysiology and treatment of depressive disorders. At the same time, the therapeutic effect of physical activity seems to work via immunomodulatory pathways. The interventional study "Mood Vibes" analyzed the influence of exercise on depression severity (primary endpoint) in depressive adolescents; the influence of PICs on the clinical outcome was analyzed as a secondary endpoint. METHODS: Clinically diagnosed depressed adolescents (N = 64; 28.1% male; mean age = 15.9; mean BMI = 24.6) were included and participated either in Whole Body Vibration (WBV) (n = 21) or bicycle ergometer training (n = 20) in addition to treatment-as-usual (TAU). Patients in the control treatment group received TAU only (n = 23). The PICs (interleukin-6-IL-6 and tumor necrosis factor-α-TNF-α) were analyzed before intervention, after 6 weeks of training (t1), and 8 weeks post-intervention (t2). The effects of the treatment on depression severity were rated by self-rating "Depression Inventory for Children and Adolescents" (DIKJ). RESULTS: Basal IL-6 decreased in all groups from t0 to t1, but it increased again in WBV and controls at t2. TNF-α diminished in ergometer and controls from baseline to t1. PIC levels showed no correlation with depression severity at baseline. The influence on DIKJ scores over time was significant for IL-6 in the WBV group (p = 0.008). Sex had an impact on TNF-α (p < 0.001), with higher concentrations in male patients. Higher body mass index was associated with higher IL-6 concentrations over all measurement points (p < 0.001). CONCLUSIONS: The positive effects of an intensive add-on exercise therapy on adolescent depression seem to be partly influenced by immunomodulation. A small sample size and non-randomized controls are limitations of this study.

Physical Activity for the Treatment of Adolescent Depression: A Systematic Review and Meta-Analysis.

Background: A noticeable proportion of adolescents with depression do not respond to guideline recommended treatment options. This systematic review and meta-analysis investigated the effectiveness of physical activity interventions as an alternative or complementary treatment for adolescents (12-18 years) with depression. The characteristics of the physical activity treatment that were most effective in reducing symptoms in adolescents with depression and the impact of methodological shortcomings in the existing research were also examined. Methods: Medline, PsycINFO, SPORTDiscus, ProQuest, and CENTRAL were searched for eligible records. Effect size estimates were pooled based on the application of a random-effects model. Potential moderation by physical activity characteristics (i.e., intensity, type, context, and time frame) and methodological features (i.e., type of control group and diagnostic tool to identify depression at baseline) was investigated by means of subgroup analyses and meta-regressions. The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was the antidepressant effect of physical activity at postintervention measurement time point. As secondary outcomes, the sustainability of effects after the end of physical activity treatment and the acceptability of physical activity treatments were assessed. Overall, 10 studies were included in the qualitative synthesis and 9 studies involving 431 patients were included in the quantitative synthesis. Results: A moderate, significant antidepressant effect of physical activity was found (Hedges' g = -0.47, 95% CI = -0.71 to -0.24). Heterogeneity was small (T2 = 0.0313, I 2 = 27%, p = 0.18). However, the certainty of evidence was downgraded to low because the included studies contained serious methodological limitations. Moderator analyses revealed that session intensity significantly moderated the antidepressant effect of physical activity. Moreover, noticeably smaller effect sizes were found in studies that used non-physical activity sham treatments as control treatments (e.g., playing board games), compared to studies that used no control group treatments. Only three studies assessed the sustainability of effects after the end of physical activity treatment. The results suggest that the antidepressant effects further increase after the end of physical activity interventions. There was no significant difference in dropout risk between the physical activity and control groups. Conclusions: This review suggests that physical activity is effective in treating depression in adolescents. Physical activity sessions should be at least moderately intense [rate of perceived exertion (RPE) between 11 and 13] to be effective. Furthermore, our results suggest that physical activity treatments are well accepted. However, the low methodological quality in included studies might have led to effect overestimation. Therefore, more studies with higher methodological quality are needed to confirm the recommendation for physical activity treatments in adolescents with depression.

Effects of a 6-week, whole-body vibration strength-training on depression symptoms, endocrinological and neurobiological parameters in adolescent inpatients experiencing a major depressive episode (the "Balancing Vibrations Study"): study protocol for a randomized placebo-controlled trial.

BACKGROUND: Moderate to vigorous endurance and strength-training exercise was suggested as a treatment option for major depression. However, there is little evidence to support this suggestion in adolescent patients. The present study investigates the effects of a whole-body vibration strength-training intervention on symptoms in medication-naïve adolescent inpatients experiencing a major depressive episode. Potential underlying endocrinological and neurobiological mechanisms are explored. METHODS/DESIGN: A double-blinded randomized controlled trial is conducted at the University Hospital of Cologne in Germany, comparing a 6-week, whole-body vibration strength-training with a 6-week placebo-intervention, as add-on therapy to inpatient treatment as usual. Forty-one subjects (13-18 years of age) will be included in each of the two groups. The study is powered to detect (α = .05, ß = .2) a medium effect size difference between the two groups (d = .5) in terms of patients' change in the Children's Depression Rating Scale raw-score, from baseline until the end of the intervention. As secondary endpoints, the effects of exercise treatment on patients' cortisol awakening response as well as on brain-derived neurotrophic factor, insulin-like growth factor 1 and inflammatory markers (tumor necrosis factor-alpha, interleukin-6 and C-reactive protein) serum levels will be assessed. DISCUSSION: This study will provide evidence on the effectiveness of whole-body vibration strength-training as an add-on therapy in adolescent inpatients experiencing a major depressive episode. After completion of data collection, the present study will be the largest randomized controlled trial so far to investigate the effectiveness of an exercise intervention in inpatient adolescents suffering from a major depressive episode. Moreover, the present study may help to determine the underlying mechanisms of potential anti-depressant effects of exercise in depressed adolescent inpatients. TRIAL REGISTRATION: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00011772 . Registered on 20 March 2017.

Whole body vibration added to treatment as usual is effective in adolescents with depression: a partly randomized, three-armed clinical trial in inpatients.

There is growing evidence for the effectiveness of exercise in the treatment of adult major depression. With regard to adolescents, clinical trials are scarce. Due to the inherent symptoms of depression (lack of energy, low motivation to exercise), endurance training forms could be too demanding especially in the first weeks of treatment. We hypothesized that an easy-to-perform passive muscular training on a whole body vibration (WBV) device has equal anti-depressive effects compared to a cardiovascular training, both administered as add-ons to treatment as usual (TAU). Secondly, we presumed that both exercise interventions would be superior in their response, compared to TAU. In 2 years 64 medication-naïve depressed inpatients aged 13-18, were included. Both exercise groups fulfilled a supervised vigorous training for 6 weeks. Depressive symptoms were assessed by self-report ("Depressions Inventar für Kinder und Jugendliche"-DIKJ) before intervention and after weeks 6, 14 and 26. Compared to TAU, both groups responded earlier and more strongly measured by DIKJ scores, showing a trend for the WBV group after week 6 (p = 0.082). The decrease became statistically significant for both intervention groups after week 26 (p = 0.037 for ergometer and p = 0.042 for WBV). Remission rates amounted to 39.7% after week 6 and 66% after week 26, compared to 25% after week 26 in TAU. These results provide qualified support for the effectiveness of exercise as add-on treatment for medication-naïve depressed adolescents. The present results are limited by the not randomized control group.

A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome.

Warburg Micro syndrome and Martsolf syndrome are clinically overlapping autosomal recessive conditions characterized by congenital cataracts, microphthalmia, postnatal microcephaly, and developmental delay. The neurodevelopmental and ophthalmological phenotype is more severe in Warburg Micro syndrome in which cerebral malformations and severe motor and mental retardation are common. While biallelic loss-of-function mutations in RAB3GAP1 are present in the majority of patients with Warburg Micro syndrome; a hypomorphic homozygous splicing mutation of RAB3GAP2 has been reported in a single family with Martsolf syndrome. Here, we report a novel homozygous RAB3GAP2 small in-frame deletion, c.499_507delTTCTACACT (p.Phe167_Thr169del) that causes Warburg Micro syndrome in a girl from a consanguineous Turkish family presenting with congenital cataracts, microphthalmia, absent visually evoked potentials, microcephaly, polymicrogyria, hypoplasia of the corpus callosum, and severe developmental delay. No RAB3GAP2 mutations were detected in ten additional unrelated patients with RAB3GAP1-negative Warburg Micro syndrome, consistent with further genetic heterogeneity. In conclusion, we provide evidence that RAB3GAP2 mutations are not specific to Martsolf syndrome. Rather, our findings suggest that loss-of-function mutations of RAB3GAP1 as well as functionally severe RAB3GAP2 mutations cause Warburg Micro syndrome while hypomorphic RAB3GAP2 mutations can result in the milder Martsolf phenotype. Thus, a phenotypic severity gradient may exist in the RAB3GAP-associated disease continuum (the "Warburg-Martsolf syndrome") which is presumably determined by the mutant gene and the nature of the mutation.

[The impact of emotional stimuli on working memory in female delinquent juveniles]. / Der Einfluss emotionaler Stimuli auf die Arbeitsgedächtnisleistung bei weiblichen delinquenten Jugendlichen.

OBJECTIVE: This paper focuses on the objective to what extent detained girls exhibit deficits with respect to spatial working memory. Moreover, this study investigates the influence of visual emotional stimuli on the working memory of antisocial female juveniles as well as the relationship between the number of errors in performing the different working memory tasks and psychopathy. METHODS: A group of incarcerated female adolescents (n = 33) was compared with a group of non-delinquent students attending grades 10 and 11 of an integrated comprehensive school (n = 20). Three variants of the Subject-Ordered Pointing Task (SOPT: neutral, erotic-, fear-related) and the Psychopathy-Checklist Youth Version (PCL:YV) were administered to the two groups. RESULTS: Analyses of variance showed significant differences between the two groups regarding the neutral and the fear-related variants of the SOPT, but none regarding the erotic-related variant. Hypothesized associations between psychopathy and the neutral variant were affirmed, but not for the fear-related variant of the SOPT. CONCLUSIONS: This study demonstrated similar deficits with respect to neutral working memory in detained female juveniles as have been affirmed for male antisocials within the literature. On the one hand, the expected levelling of the group difference regarding working memory accomplishment in the erotic variant could be explained by an improvement of the often sexually traumatized delinquent female adolescents, and on the other hand by impairment in the control group. The results with respect to working memory accomplishment on the basis of fear-related stimuli indicated that girls with high psychopathy scores differ from antisocial boys and might still react susceptible to emotional stimuli.