The presence of different clinical symptoms in patients with treatment-resistant depression (TRD) of different sexes may be related to different neuropathological mechanisms. A total of 16 male patients with TRD, 18 female patients with TRD, 18 male healthy controls (HCs) and 19 female HCs completed this study. We used the amplitude of low frequency fluctuations (ALFF) method to analyze the results. Moreover, the correlation between abnormal brain areas and clinical symptoms in different sexes of the TRD groups was also analyzed. The effects of the sex-by-group interaction difference in ALFF among the four groups was located in the left middle frontal gyrus, left precentral gyrus and left precuneus. Post hoc comparisons revealed that the male TRD group had lower ALFF in the left middle frontal gyrus and left precentral gyrus compared with the female TRD group. There was a positive correlation between the left middle frontal gyrus, the left precuneus and the 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores, and a negative correlation between the left precentral gyrus and the HAMD-17 scores in the female TRD group. This study will provide some clinical reference value for the sex differences in neuropathological mechanisms of TRD.

Chronic pain is a prevalent health issue with high disability rates, and traditional pharmacological treatments often come with limitations such as dependency and side effects. Transcutaneous auricular vagus nerve stimulation (taVNS), as an emerging non-invasive neuromodulation technique, has demonstrated broad application prospects in chronic pain management in recent years. This systematic review examines the clinical efficacy of taVNS across multiple chronic pain conditions, including neuropathic pain, autoimmune disease-related pain, gastrointestinal pain, and musculoskeletal pain. It also delves into its neurobiological mechanisms, primarily involving activation of central descending pain control pathways, modulation of cholinergic anti-inflammatory pathways, balancing autonomic nervous system function, reshaping functional connectivity in brain networks, regulating neurotransmitter and neuropeptide balance, and inhibiting peripheral and central sensitization processes. Despite ongoing challenges in parameter standardization, in-depth mechanism elucidation, and personalized treatment strategies, taVNS offers an innovative therapeutic approach for chronic pain patients due to its favorable safety profile, tolerability, and multi-target regulatory advantages. Future large-scale clinical studies and multidisciplinary collaboration are needed to further advance the precision application of taVNS within comprehensive pain management systems.

The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.

Background: Functional dyspepsia (FD) is a common gut–brain interaction disorder with suboptimal response to pharmacotherapy. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation targeting the vagus nerve, has emerged as a promising brain–gut axis therapy. This scoping review (PRISMA-ScR, JBI methodology) synthesizes clinical and preclinical mechanistic evidence on taVNS for FD. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched up to December 20, 2025, following PRISMA-ScR. Using PICOS (adults with FD; taVNS; sham/non-vagal/active controls; symptoms, gastric function, psychological outcomes, biomarkers; RCTs/clinical trials and controlled animal studies), two reviewers independently screened, extracted data, and assessed bias (RoB2 for RCTs, SYRCLE for animal studies). A narrative synthesis was performed due to heterogeneity. Results: Four RCTs ( n = 480) and eight preclinical rodent studies met inclusion. All RCTs showed significant improvements in dyspeptic symptoms, gastric accommodation, slow-wave normalization, and comorbid anxiety, depression, sleep disturbance versus sham/non-vagal control, sustained for 4–12 weeks. Stimulation parameters varied (10–30 Hz; 0.5–10 mA; 2–4 weeks); risk of bias low-moderate. Preclinical rodent evidence supported five interconnected candidate mechanisms: (i) autonomic balance and cholinergic modulation; (ii) α7nAChR/NF-κB anti-inflammatory pathway with duodenal barrier restoration; (iii) NGF/TrkA/PLC-γ/TRPV1-mediated visceral hypersensitivity suppression; (iv) HPA axis inhibition; (v) rebalancing of brain-gut peptides (motilin, CCK, GLP-1). Conclusion: This review characterizes taVNS as a safe, well-tolerated, mechanistically plausible non-invasive neuromodulation for FD acting on multiple brain–gut axis nodes. However, the small number of trials, parameter heterogeneity, and limited follow-up constrain definitive conclusions. Adequately powered, multicenter RCTs with standardized protocols and long-term follow-up are needed to confirm efficacy and define optimal regimens.