Major depressive disorder (MDD) is a complex neuropsychiatric condition whose multifactorial etiology remains incompletely explained by neuron-centric and neurotransmitter hypotheses alone. This review addresses that gap by positioning microglia—the CNS’s resident immune cells—as central drivers of MDD pathogenesis. We organize current evidence around five interrelated themes: hypothalamic–pituitary–adrenal (HPA) axis dysfunction, monoaminergic and kynurenine pathway imbalances, neuroinflammatory overactivation, synaptic and white-matter integrity disruption, and gut–brain axis perturbations. In MDD, microglia shift from a surveillant resting state to either an overactivated or functionally inhibited phenotype, exacerbating pathology via aberrant cytokine release, dysregulated synaptic pruning and impaired myelin support. These changes are modulated by genetic susceptibility, sex differences, environmental stressors and microbiome alterations. We then survey translational advances—traditional and novel therapeutics that modulate microglial polarization, emerging blood- and imaging-based biomarkers, and strategies to harness microglia–oligodendrocyte cross-talk for remyelination—and highlight integrative platforms for stratifying inflammation-driven versus non-inflammatory subtypes. Our principal takeaway is that microglia represent a unifying nexus and actionable target for precision interventions tailored to individual biological profiles.

The CaMK pathway has been proven to play an important role in regulating cognitive function and emotional response. Acupuncture through the CaMK pathway improves depression-like behavior and the molecular mechanism related to its antidepressant remains to be explored. In this study, we aimed to determine whether the ability of acupuncture at Baihui (GV20) and Shenting (GV24) points to treat depression is related to the regulation of key proteins in the CaMK pathway. A rat model of depression was induced by chronic unpredicted mild stress (CUMS). Model rats in the electroacupuncture group were subjected to acupuncture at the Baihui (GV20) and Shenting (GV24) acupoints once a day for 20 min. Model rats in the fluoxetine group were gavaged with fluoxetine (1.8 mg/kg). Immunohistochemistry and Western blotting assays were used to evaluate immunoreactivity for and the protein expression levels of CaMKII, CaMKIV, and CaM. The results showed that electroacupuncture had a significant effect in rats with depression. Electroacupuncture and fluoxetine regulated the expression of key proteins in the CaMK signaling pathway, which is related to depression, in the hippocampi of rats. This indicates that acupuncture at Baihui (GV20) and Shenting (GV24) may alleviate depressive symptoms and reduce work- and life-related burdens and stress by regulating the CaMK signaling pathway.

Major depressive disorder (MDD) is a common mental disorder with chronic tendencies that seriously affect regular work, life, and study. However, its exact pathogenesis remains unclear. Patients with MDD experience systemic and localized impairments in glucose metabolism throughout the disease course, disrupting various processes such as glucose uptake, glycoprotein transport, glycolysis, the tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). These impairments may result from mechanisms including insulin resistance, hyperglycemia-induced damage, oxidative stress, astrocyte abnormalities, and mitochondrial dysfunction, leading to insufficient energy supply, altered synaptic plasticity, neuronal cell death, and functional and structural damage to reward networks. These mechanical changes contribute to the pathogenesis of MDD and severely interfere with the prognosis. Herein, we summarized the impairment of glucose metabolism and its pathophysiological mechanisms in patients with MDD. In addition, we briefly discussed potential pharmacological interventions for glucose metabolism to alleviate MDD, including glucagon-like peptide-1 receptor agonists, metformin, topical insulin, liraglutide, and pioglitazone, to encourage the development of new therapeutics.

Major depressive disorder (MDD) is a highly prevalent and severely disabling psychiatric disorder that decreases quality of life and imposes substantial economic burden. Acupuncture has emerged as an effective adjunctive treatment for depression, it regulates neurotransmitters involved in mood regulation and modulates the activity of specific brain regions associated with emotional processing, as evidenced by neuroimaging and biochemical studies. Despite these insights, the precise neuroplastic mechanisms through which acupuncture exerts its antidepressant effects remain not fully elucidated. This review aims to summarize the current knowledge on acupuncture’s modulation of neuroplasticity in depression, with a focus on the neuroplasticity-based targets associated with acupuncture’s antidepressant effects. We encapsulate two decades of research into the neurobiological mechanisms underpinning the efficacy of acupuncture in treating depression. Additionally, we detail the acupoints and electroacupuncture parameters used in the treatment of depression to better serve clinical application.

Depression is one of the most burdensome diseases worldwide, garnering significant attention. The uric acid to high-density lipoprotein cholesterol ratio (UHR) is a novel and easily obtainable indicator used to assess the body’s inflammatory and metabolic status. It has attracted interest due to its potential role in the prevention and treatment of depression. This study aims to explore the potential correlation between UHR and depression. A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Depression occurrence was defined as the dependent variable, and UHR was defined as the independent variable. Multivariable logistic regression was performed to assess the relationship between the independent and dependent variables. Smooth curve fitting and threshold effect analyses were used to evaluate the nonlinear relationship and effect size between UHR and depression. Subgroup and sensitivity analyses were conducted to determine the stability of the results. This study included 24,272 adults based on NHANES data. Multivariable logistic regression analysis showed that, in the fully adjusted model, individuals with the highest UHR had a 42% increased likelihood of depression compared to those with the lowest UHR (OR = 1.42; 95% CI, 1.23–1.64; P < 0.001). Subgroup analyses indicated no significant interaction between UHR and specific subgroups (all interaction P > 0.05). Moreover, there is a nonlinear association between UHR and depression. When the UHR level was>10.21, the correlation between UHR and depression increased by 3% (OR = 1.03; 95% CI, 1.01–1.04; P < 0.01). The study found that UHR is significantly associated with a higher risk of depression among American adults. However, further prospective studies are needed to accurately elucidate the causal relationship between elevated UHR levels and depression risk. Therefore, larger cohort studies are required to support these findings.