Clinical and radiomic features for predicting the treatment response of repetitive transcranial magnetic stimulation in major neurocognitive disorder: Results from a randomized controlled trial.

Image-guided repetitive transcranial magnetic stimulation (rTMS) has shown clinical effectiveness in senior adults with co-occurring depression and cognitive impairment, yet the imaging markers for predicting the treatment response are less investigated. In this clinical trial, we examined the efficacy and sustainability of 10 Hz rTMS for the treatment of depression and cognitive impairment in major neurocognitive disorder (NCD) patients and tested the predictive values of imaging-informed radiomic features in response to rTMS treatment. Fifty-five major NCD patients with depression were randomly assigned to receive a 3-week rTMS treatment of either active 10 Hz rTMS (n = 27) or sham rTMS (n = 28). Left dorsolateral prefrontal cortex (DLPFC) was the predefined treatment target. Based on individual structural magnetic resonance imaging scans, surface-based analysis was conducted to quantitatively measure the baseline radiomic features of left DLPFC. Severity of depression, global cognition and the serum brain-derived neurotrophic factor (BDNF) level were evaluated at baseline, 3-, 6- and 12-week follow-ups. Logistic regression analysis revealed that advanced age, higher baseline cognition and randomized group were associated with the remission of depression. Increased cortical thickness and gyrification in left DLPFC were the significant predictors of clinical remission and cognitive enhancement. A 3-week course of 10 Hz rTMS is an effective adjuvant treatment for rapid ameliorating depressive symptoms and enhancing cognitive function. Pre-treatment radiomic features of the stimulation target can predict the response to rTMS treatment in major NCD. Cortical thickness and folding of treatment target may serve as imaging markers to detect the responders. ChiCTR-IOR-16008191, registered on March 30, 2016.

Peripheral Blood T Cell Gene Expression Responses to Exercise and HMB in Sarcopenia.

BACKGROUND: Sarcopenia is a major health problem in older adults. Exercise and nutrient supplementation have been shown to be effective interventions but there are limited studies to investigate their effects on the management of sarcopenia and its possible underlying mechanisms. Here, we studied T cell gene expression responses to interventions in sarcopenia. METHODS: The results of this study were part of a completed trial examining the effectiveness of a 12-week intervention with exercise and nutrition supplementation in community-dwelling Chinese older adults with sarcopenia, based on the available blood samples at baseline and 12 weeks from 46 randomized participants from three study groups, namely: exercise program alone (n = 11), combined-exercise program and nutrition supplement (n = 23), and waitlist control group (n = 12). T cell gene expression was evaluated, with emphasis on inflammation-related genes. Real-time PCR (RT-PCR) was performed on CD3 T cells in 38 selected genes. Correlation analysis was performed to relate the results of gene expression analysis with lower limb muscle strength performance, measured using leg extension tests. RESULTS: Our results showed a significant improvement in leg extension for both the exercise program alone and the combined groups (p < 0.001). Nine genes showed significant pre- and post-difference in gene expression over 12 weeks of intervention in the combined group. Seven genes (RASGRP1, BIN1, LEF1, ANXA6, IL-7R, LRRN3, and PRKCQ) showed an interaction effect between intervention and gene expression levels on leg extension in the confirmatory analysis, with confounder variables controlled and FDR correction. CONCLUSIONS: Our findings showed that T cell-specific inflammatory gene expression was changed significantly after 12 weeks of intervention with combined exercise and HMB supplementation in sarcopenia, and that this was associated with lower limb muscle strength performance.

Genetic Overlap Between Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in SHANK2 Gene.

Background: Recent findings indicated a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), as well as shared genetic influences on them. The latter might contribute at least partly to the former clinical scenario. This study aimed at investigating whether SHANK genes were potential pleiotropic genes to the two said disorders, underlying their genetic overlap. Methods: This study recruited 298 boys with ADHD (including 256 family trios of 1 ADHD boy and his 2 biological parents), 134 boys with ASD, 109 boys with both ADHD and ASD, and 232 typically developing boys as community controls. They were aged between 6 and 11 years old. Results: There was no significant difference in allele frequency of a number of single nucleotide polymorphisms (SNPs) in SHANK2/SHANK3 between the three clinical groups (ADHD, ASD, and ADHD + ASD) and between the two control groups (community controls and pseudo-controls), respectively. The three clinical groups and the two control groups were thus, respectively, combined. A comparison between the two aggregated samples identified significant evidence of disease association for three SHANK2 SNPs with both ADHD and ASD, even after multiple testing correction: rs11236616 (OR = 0.762, permuted p = 0.0376), rs7106631 (OR = 0.720, permuted p = 0.0034), and rs9888288 (OR = 0.770, permuted p = 0.0407). Comparisons among individual groups pointed to a similar trend of findings. Conclusion: SHANK2 could be considered a potential pleiotropic gene underlying the genetic overlap between ADHD and ASD. This might contribute partly to their high comorbidity in the afflicted children.