We investigated whether changes through doubling the duration of each tDCS session would increase efficacy of tDCS for depression. tDCS was applied for 10 sessions, followed by two additional weekly sessions. 63 patients with MDD underwent randomization, with 22 being assigned to 60-min/d group, 25 to 30 min/d group, and 16 to sham group. HAMD-17 reductive ratios at week 2 and 4 were of no significant differences among treatment groups. 60 min group had a greater decrease in anxiety compared to 30 min group and sham group based on HAMA at 4 weeks but only in the completer analysis, not in ITT analysis.

Background: Restless legs syndrome (RLS) is a common sensorimotor sleep disorder that affects sleep quality of life. Much effort has been made to make progress in RLS pharmacotherapy; however, patients with RLS still report poor long-term symptom control. Methods: Comprehensive Mendelian randomization (MR) was performed to search for potential causal genes and drug targets using the cis-pQTL and RLS GWAS data. Robustness was validated using the summary-based Mendelian randomization (SMR) method and co-localization analysis. Further evidence of pleiotropy of the target genes and their potential side effects was provided by phenome-wide MR analysis (MR-PheWAS). Finally, molecular docking simulations were conducted on drug candidates corresponding to these targets, which revealed promising binding affinities and interaction patterns and underscored the druggable potential of the target gene. All of the analyses above were conducted in the context of Homo sapiens. Results: MAN1A2 showed a statistically significant result in the MR analysis, which was validated through SMR and co-localization analysis. The MR-PheWAS showed a low probability of pleiotropy and prospective side effects. Molecular docking was used to visualize the binding structure and fine affinity for MAN1A2 and the drugs predicted by DSigDB. Conclusions: Our study provides comprehensive evidence supporting MAN1A2 as a promising causal gene and therapeutic target for RLS, offering insights into the underlying molecular mechanisms and paving the way for future drug development efforts.

The endophenotype of insomnia disorder is complex and the treatment is not targeted. The data-driven typing method might provide some bases for precise treatment. The present study was based on a post hoc analysis, aiming to explore the association between subtypes of insomnia disorder and the efficacy of cognitive-behavioral therapy for insomnia (CBT-I). The present study was conducted on data of 118 patients with chronic insomnia disorder combined mild anxiety or/and depressive symptoms, who had completed an 8-week randomized controlled trial of CBT-I vs CBT-I plus (CBT-I combined with modules targeting anxiety and depressive symptoms). The silhouette coefficient determined the optimal number of clusters, and a K-means clustering analysis was performed. T-tests were conducted to assess baseline differences at eight weeks, and the changes in self-reported total sleep time (sTST), Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HRSD-17), and Hamilton Anxiety Rating Scale (HAMA) scores in order to explore the impact of subtypes and treatment approaches (CBT-I and CBT-I plus) on insomnia and emotional symptoms. The analysis revealed no significant demographic differences between the two clusters. Subtype 2 was characterized by significantly poorer baseline sleep quality (PSQI: 16.59 vs 12.74, t = -9.90, p < 0.01), higher depressive (HRSD: 18.47 vs 13.21, t = -8.37, p < 0.01), and anxiety levels (HAMA: 17.47 vs 13.46, t = -6.23, p < 0.01), and shorter sTST (4.67 vs 6.09 h, t = 8.31, p < 0.01) compared to Subtype 1. Post-treatment analyses showed significant improvements in both subtypes, with Subtype 2 experiencing a larger increase in sleep duration (csTST: 0.58 vs 1.77 h, t = -7.18, p < 0.01) and more pronounced improvements in sleep quality (cPSQI: 6.92 vs 8.88, t = -3.57, p < 0.001), depression (cHRSD: 8.07 vs 10.59, t = -2.71, p = 0.008), and anxiety (cHAMA: 9.28 vs 11.22, t = -2.56, p = 0.012). Despite these improvements, Subtype 1 maintained significantly better outcomes in sleep quality (PSQI: 5.81 vs 7.71, p < 0.01), depression (HRSD: 5.14 vs 7.89, p < 0.01), and anxiety (HAMA: 4.18 vs 6.25, p < 0.01) at 8 weeks. No significant differences in baseline characteristics were found between treatment groups within subtypes, indicating homogeneity. Within Cluster 1, CBT-I plus was more effective in reducing depressive symptoms (cHRSD: t = -2.48, p = 0.016), whereas CBT-I was superior in enhancing sTST in Cluster 2 (t = 2.01, p = 0.049), with no significant differences in other measures. The study underscores the heterogeneity within ID subtypes and the differential response of sleep quality and depressive symptoms to CBT-I and CBT-I plus, highlighting the importance of personalized treatment strategies based on insomnia subtypes.