Evaluating a case-based mental health course for pediatricians in the UAE: a prospective study.

Depression, a highly debilitating mental health disorder, has become a critical global public health issue, accounting for the greatest disease burden among psychiatric conditions (). According to the World Health Organization, more than 350 million people worldwide suffer from depression, and it is projected to become the leading cause of disease burden by 2030 (; ). Notably, approximately 50%–75% of individuals with depression exhibit significant social avoidance behavior, a core symptom that severely impairs social functioning and quality of life (). However, the underlying mechanisms of social avoidance behavior in depression remain poorly understood, and few studies have specifically focused on this behavioral dimension. In recent years, the microbiota-gut-brain axis (MGBA) has gained recognition as a pivotal pathway implicated in the pathophysiology of depression, offering a novel insight for investigating behavioral symptomatology (). Conventional pharmacological interventions for social avoidance behavior, such as selective serotonin reuptake inhibitors, although effective, are often associated with long-term adverse effects including gastrointestinal discomfort, which may compromise treatment adherence and efficacy (). In contrast, traditional Chinese medicine formulas (TCMFs), characterized by multi-component nature, holistic therapeutic approach, and fewer adverse effects, have demonstrated efficacy in improving social avoidance behavior (; ). Xiaoyaosan, a classical TCM prescription documented in “” from the Song Dynasty, is widely used to soothe the liver and relieve depressive symptoms (; ). Our previous work revealed that the adverse reactions of Xiaoyaosan decoction, such as dry mouth and sensation of dryness, were suspected to be associated with . Additionally, chemical composition attribution analysis showed that contributed minimally to the antidepressant effect, and its spleen-strengthening function overlapped with that of . Therefore, both and were removed to generate the modified formulation of Modified Xiaoyaosan (MXYS). The optimized composition comprises six medicinal herbs: , , , , , and (). Our previous studies have shown that MXYS significantly improves social avoidance behavior in chronic social defeat stress (CSDS) mice (). MXYS offers a comprehensive treatment alternative for patients with mild to moderate depression, exhibiting multi-target and multi-pathway mechanisms that underscore the systemic therapeutic advantages of TCMFs in managing complex neuropsychiatric conditions. Recent multi-omics studies have demonstrated that natural products and herbal extracts can ameliorate disease phenotypes by remodeling gut microbiota and restoring metabolic homeostasis (; ; ). For instance, dietary cherry juice alleviates obesity by resolving gut microbiota dysbiosis and elevating tight junction proteins (). Similarly, polysaccharide restores immunosuppression through a coordinated axis of gut barrier restoration, microbiota remodeling, and systemic metabolic regulation (). These studies are crucial for understanding how complex Chinese herbal compounds play a multi-target role. A key mechanism linking gut dysfunction to depression involves increased intestinal permeability, which disrupts MGBA homeostasis and facilitates systemic inflammation. A seminal review emphasized that intestinal hyperpermeability contributes to brain-gut axis dysregulation and that therapeutic restoration of barrier integrity may improve symptoms of extraintestinal disorders, including depression (). TCMFs may exert protective effects on the intestinal barrier through anti-inflammatory activity, modulation of gut microbiota, and enhancement of epithelial repair, thereby potentially ameliorating behavioral deficits such as social avoidance. This approach represents a promising integrated strategy for concurrent gut-brain intervention, though further mechanistic and clinical validation is required.