Acupuncture Modulates Neurotransmitter-Related Molecules in the Amygdala to Ameliorate Generalized Anxiety Disorder.

Abstract

BACKGROUND: Neurotransmitter imbalance is a key mechanism contributing to the heightened negative emotions and anhedonia associated with anxiety disorders. However, whether acupuncture exerts its anxiolytic effects by modulating neurotransmitter imbalance remains unclear. METHODS: Seventy generalized anxiety disorder (GAD) patients were recruited and randomly assigned to acupuncture or wait-list groups. The Hamilton Anxiety Rating Scale (HAMA) and fMRI scans were used before and after treatment to assess anxiety levels and brain activity. In parallel, male Sprague-Dawley rats were divided into four groups: control, chronic unpredictable stress model (CUS), electroacupuncture (EA), and sham acupuncture (SA). The EA group received stimulation at specific acupuncture points over 21&#x2009;days, while the CUS group experienced chronic unpredictable stress to induce anxiety. Behavioral assessments and molecular analyses, including qRT-PCR, Western blotting, and immunofluorescence, measured neurotransmitter levels. RESULTS: Clinically, the acupuncture group exhibited a significant reduction in HAMA scores compared to baseline (p&#x2009;<&#x2009;0.001), unlike the wait-list group. fMRI results indicated decreased ReHo in brain regions such as the amygdala, hippocampus, anterior and posterior cingulate cortices, putamen, and precuneus following acupuncture (GRF-corrected p-cluster <&#x2009;0.05). These reductions showed overlap in the anterior and posterior cingulate cortices between both groups. A positive correlation was found between reduced ReHo in the amygdala and the decrease in HAMA scores (rs&#x2009;=&#x2009;0.390, p&#x2009;=&#x2009;0.023), while a negative correlation was observed between reduced ReHo in the hippocampus and illness duration (rs&#x2009;=&#x2009;-0.385, p&#x2009;=&#x2009;0.025). In the animal model, EA improved body weight and reduced anxiety-like behaviors (p&#x2009;<&#x2009;0.05). EA increased IGF-1 expression in the mPFC and amygdala, and decreased NR2B, GluR2 in the amygdala (p&#x2009;<&#x2009;0.05). CONCLUSION: Acupuncture shows potential in treating anxiety disorders by modulating IGF-1 and NR2B expression, thus restoring neurotransmitter balance in the mPFC-amygdala pathway. In both animal models and clinical settings, acupuncture effectively reduced anxiety symptoms and induced positive changes in brain regions such as the amygdala and hippocampus. These findings provide preliminary evidence for using acupuncture in the treatment of GAD. CLINICAL TRIAL NUMBER: MR-46-23-043956.