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Major depressive disorder (MDD) is a severe mental health disorder that is projected to become the most widespread and financially burdensome illness across the globe by 2030.
While advances in antidepressant treatments have been significant, doctors still lack clear, objective methods for determining which medication will work best for each person. Nearly one-third of patients experience little to no improvement from their first prescribed antidepressant, making personalized treatment an ongoing challenge.
A recent study published in General Psychiatry examined whether traditional Chinese medicine (TCM) could offer an alternative approach for treating MDD. The researchers also identified a specific brain network, visible through MRI scans, that could predict how much a patient’s symptoms or blood biomarkers would improve following treatment.
The clinical trial was randomized, double-blind, and placebo-controlled, involving 28 outpatients diagnosed with MDD at the Fourth People’s Hospital of Taizhou. Participants were divided into two groups: one received the Yueju Pill (a traditional herbal formula used in Chinese medicine that contains ingredients such as Cyperus, Gardenia, and Atractylodes, traditionally believed to regulate mood and relieve emotional stagnation) along with a placebo for escitalopram, while the other group took escitalopram, a common antidepressant, along with a placebo for Yueju Pill.
Researchers assessed depression levels using the 24-item Hamilton Depression Scale (HAMD-24) and collected both blood samples and MRI brain scans to evaluate treatment effects.
Brain network predictors of depression improvement after antidepressant treatment. Credit: Yuxuan Zhang, Yiwei Ren, Gang Chen, Haosen Wang, Jinlin Miao, Bo Cui, Zhilu Zou, Jin Feng, Chunkou Hong, Mingzhi Han, Jinhui Wang.
Yueju Pill’s Distinct Effects
Both groups showed improvement in their depression symptoms after treatment. However, only the Yueju Pill group showed a significant increase in serum brain-derived neurotrophic factor (BDNF)—a protein associated with brain health and mood regulation. From the brain imaging results, researchers found that certain brain structure networks could predict changes in depression scores for both groups.
Interestingly, some specific brain network patterns—based on sulcus depth and cortical thickness—were only predictive in the Yueju Pill group. Further analysis showed that the visual network of the brain played an important role in predicting both changes in depression scores and BDNF levels for those taking Yueju Pill.
This study suggests that brain network patterns could help predict how well individual patients with MDD respond to Yueju Pill treatment. This finding may help clinical workers personalize antidepressant therapy in the future.
“The brain networks can then be fed to the predictive models constructed in this study to predict patients’ responses to Yueju Pill treatment,” explained Dr. Zhang, the study’s leading author. “Based on the predicted responses, we can then determine whether the patient is suitable for Yueju Pill treatment.”
Reference: “Brain network predictors of changes in symptoms and serum BDNF following antidepressant treatment with escitalopram and Yueju Pill in major depressive disorder: a randomised, double-blind, placebo-controlled pilot study” by Yuxuan Zhang, Yiwei Ren, Gang Chen, Haosen Wang, Jinlin Miao, Bo Cui, Zhilu Zou, Jin Feng, Chunkou Hong, Mingzhi Han and Jinhui Wang, 13 October 2025, General Psychiatry.
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