The effect of acupuncture on depression and its correlation with metabolic alterations: A randomized controlled trial

Abstract

Background: Electroacupuncture (EA) treatment has antidepressant effect and when patients were treated with EA and antidepressants, the effect could be maintained for a longer time. However, the effect of EA combined with antidepressants based on metabolism is still in the initial observation stage, which requires further research.

Methods: A total of 60 patients with moderate depression were assigned into 2 groups at a ratio of 1:1, the EA group (receiving EA and antidepressants) and the control group (taking antidepressants only) in this randomized controlled pilot trial. The EA treatment was performed 3 times a week for 8 consecutive weeks and then follow up for 4 weeks. The patients' depressive mood was measured by the Hamilton Depression scale (HAMD) at baseline, week 4, week 8 and week 12. Before and after 8-week treatment, morning urine samples from all patients were analyzed by the gas chromatography-mass spectrometry (GC-MS) to find possible metabolic markers of depression and of EA treatment related changes.

Results: Compared with the control group, the EA group showed more significant improvements in depressive symptoms measured by HAMD at week 4 (16.89 ± 5.74 vs 25.58 ± 7.03, P < .001), week 8 (9.59 ± 5.13 vs 25.04 ± 7.49, P < .001) and week 12 (11.07 ± 6.85 vs 27.25 ± 7.14, P < .001). The significant differences in urinary specific metabolites before and after EA treatment were malonic acid (fatty acid biosynthesis), cysteine (glutamate metabolism), glutathione (glutamate metabolism), tryptophan (tryptophan metabolism), proline (glutamate metabolism), and N-acetyl-5-hydroxytryptamine. These metabolites are involved in tryptophan metabolism, glutamate metabolism, and fatty acid biosynthesis.

Conclusion: EA treatment combined with antidepressants is more effective in improving depressive symptoms than antidepressants alone. EA may treat depression by acting on tryptophan metabolism, glutamate metabolism, and fatty acid biosynthesis.

Trial registration: Chinese Clinical Trial Registry: ChiCTR-2000030786.

Figure 1

CONSORT flowchart of the trial.

Figure 2

PCA plots of EA group and control group. The green dots presented the post-treatment situations, and the red ones presented the pretreatment situations. PCA plots showed the distribution of metabolic components before and after being treated in (A) the EA group and (B) control group. Similar ingredients will show a certain degree of aggregation. The clearer the dot boundaries of different colors were, the greater the differences in composition were.

Figure 3

PLS-DA plots, permutation tests, OPLS-DA plots of EA group and control group. PLS-DA plots were used when the sample size was in a small number. It amplificated the separation between pre-therapy group and post-therapy group. Furthermore, to minimize the effect of intra-group differences, the pairwise PLS-DA score plots were used to demonstrate farther statistical differences between the pre-therapy group and post-therapy group of (A) the EA group (R²X = 0.508, R²Y = 0.786, Q² = 0.568), and of (B) the control group (R²X = 0.769, R²Y = 0.989, Q² = 0.94). Permutation tests were thus conducted to validate the quality of the PLS-DA models of (C) the EA group and (D) the control group. Under the premise that the PLS-DA model is valid, this study further removed the information irrelevant to the experiment by using OPLS-DA. Each point is distributed according to variable importance in the projection value (VIP). Metabolites with VIP values > 1.5 and P values < .05 in (E) the EA group and (F) the control group were deemed to be statistically significant according to the OPLS-DA model.

Figure 4

ROC curves and AUCs of the potential biomarkers. The data were statistically significant when the AUCs were higher than 0.7, demonstrating significance in clinical diagnostics. ROC curves and AUCs of the potential biomarkers as cysteinylglycine, dehydroascorbic acid, glutathione, malonic acid, N-acetyl-5-hydroxytryptamine, proline, and tryptophan of urine samples was as followed. AUC (malonic acid) = 0.913, AUC (dehydroascorbic Acid) = 0.858, AUC (N-acetyl-5-hydroxytryptamine) = 0.814, AUC (cysteinylglycine) = 0.768, AUC (glutathione) = 0.8, AUC (proline) = 0.829, AUC (tryptophan) = 0.706. The rest metabolites whose AUCs were below 0.7 would be presented in the appendix.