Bewegung als Neuromodulator: Wie körperliche Aktivität die Physiologie der adoleszenten Depression reguliert

<jats:p> Zusammenfassung: In der Behandlung der adoleszenten Depression gewinnt körperliche Aktivität aufgrund der Auswirkungen auf die Neuropathologie an Bedeutung. Aktuelle wissenschaftlichen Erkenntnisse zeigen, dass körperliches Training auf die biologischen Auswirkungen von Depression im Jugendalter einwirkt. Neben psychosozialen und genetischen Einflüssen werden verschiedene neurobiologische Faktoren diskutiert. Eine Störung der Hypothalamus-Hypophysen-Nebennieren-Achse (HHN-Achse) mit einer anhaltend erhöhten Konzentration von Kortisol gehört zu den Erklärungsmodellen. Neuere Studien sehen neuroimmunologische Prozesse und eine verminderte Konzentration an Wachstumsfaktoren als ursächlich. Diese Veränderungen könnten sowohl zu einem Ungleichgewicht in der Erregungs- und Hemmungsbalance der Hirnrinde führen als auch hirnmorphologische Veränderungen bedingen. Regelmäßiges körperliches Training scheint der Dysregulation der HHN-Achse entgegenzuwirken und die Kortisolspiegel zu normalisieren. Die Freisetzung von pro-inflammatorischen Zytokinen wird gehemmt und die Expression von Wachstumsfaktoren zur Neurogenese im adulten Gehirn angeregt. Mit der Gestaltung des sportlichen Trainings (Ausdauer- oder Kraftsport, Gruppen- oder Einzelsport, Häufigkeit, Dauer, Intensität), sollte erreicht werden, dass biologische und psychosoziale Faktoren synergistisch zusammenwirken. Diese offenen Fragen gilt es zu lösen, wenn es um die Integration sportlicher Aktivität in die Leitlinien zur Behandlung depressiver Störungen bei Kindern und Jugendlichen geht. </jats:p&gt

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

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 sus-tained 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

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

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-naive 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 (alpha = .05, beta= .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

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

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

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-alpha-TNF-alpha) 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-alpha 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-alpha (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

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-na < ve 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 fur 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-na < ve depressed adolescents. The present results are limited by the not randomized control group