Dense Cranial Electroacupuncture Stimulation for Depression: Its Clinical Efficacy and Neuroimaging Evidence from Randomized Controlled Studies

This dissertation, "Dense Cranial Electroacupuncture Stimulation for Depression: Its Clinical Efficacy and Neuroimaging Evidence From Randomized Controlled Studies" by Hung-bun, Hung, 洪鴻彬, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Major depressive disorder (MDD) is a prevalent and disabling disorder worldwide and in Hong Kong. It can occur alone or as a psychiatric sequelae of stroke known as post stroke depression (PSD). Our recent randomized controlled trial (RCT) found that additional dense cranial electroacupuncture stimulation (DCEAS) produced significantly greater improvement on depressive symptoms in patients with MDD compared to conventional antidepressants alone. However, the effectiveness of DCEAS on PSD and the underlying neural mechanism of its antidepressant effects remain unclear and need further investigation. This thesis consisted of three studies aimed to evaluate the efficacy of DCEAS as an additional therapy in PSD and to explore the neuroimaging correlates of DCEAS in MDD using PET and fMRI modalities. The purpose of Study 1 was to examine whether additional DCEAS was effective in treating PSD. A single blind RCT was conducted in 43 PSD patients treated with antidepressants and same body acupuncture combined with sham or active DCEAS with 3 acupuncture sessions per week for 4 weeks. Clinical outcomes included the Hamilton Depression Rating Scale 17-Item (HAMD-17), Clinical Global Impression - Severity Scale (CGI-S), and Barthel Index (BI).The results showed that DCEAS significantly reduced HAMD-17 at week 1, CGI-S at week 1 and endpoint whereas BI was more significantly decreased in control group. A combination of DCEAS and body acupuncture can be considered as an augmenting treatment for PSD. Study 2 aimed to explore the potential effects of DCEAS in regulating abnormal glucose metabolism in patients with MDD using 18F-FDG PET/CT. A single blind RCT was conducted in 25 MDD patients treated with antidepressants combined with sham or active DCEAS with 3 acupuncture sessions per week for 6 weeks. Clinical outcomes were measured using the HAMD-17, Zung Self-Rating Depression Scale (SDS), CGI-S and Insomnia Severity Index (ISI). There was a significant difference on the slope in SDS in linear mixed model analysis, indicating a faster improvement in subjective depressive symptoms by DCEAS. While the increased 18F-FDG signals in the cerebellum were normalized in both groups, the reversion of the reduced 18F-FDG signals in the left prefrontal cortex was only observed in DCEAS-treated patients, suggesting that additional DCEAS could more vigorously improve abnormal brain glucose metabolism in MDD. The purpose of Study 3 was to further investigate the neuropsychological and functional neuroimaging correlates of the antidepressant effects of DCEAS in the same pool of MDD subjects in Study 2 using fMRI with sad-face paradigm. The sad-face stimulation increased BOLD signals in an extensive neural network of the brain, including the frontal, temporal, parietal, limbic system and cerebellum. Additional DCEAS extensively suppressed the abnormal BOLD signals in these brain regions, more apparently in left caudate and cingulate, whereas sham treatment had slightly suppressive effects in fewer brain regions, suggesting that additional DCEAS could more robustly alter the biases towards sadness in MDD. In conclusion, DCEAS additional treatment is more effective in reducing depressive symptoms in patients with PSD, improving brain glucose metabolism and normalizing the abnormal neural activation due to biases toward