Exploration Of Acupuncture Antidepressant Mechanism Based On Magnetic Resonance Multimodal Analysis

BackgroundDepression was regarded as a major mental disorder in the world due to its high prevalence,severe clinical consequence,harm to young adults and lack of intervention.The disrupted physical stability of the central nervous system is one of the main manifestations,and then causing multi-system dysfunction.During the past thirty years,almost forty kinds of antidepressants have come out,but there are still nearly 30%of the patients,who did not show any response to all the medicine.Some of them have to change or stop the therapy for the severe side-effect.Mounting evidence have approved the curative effect of acupuncture in treating depression,and the characteristics of wide applicable,indeed curative effect,less side-effect and economical.It has provided a new direction in clinical intervention for depression.Basing on the previous confirmation of the effectiveness of acupuncture in treating depression,I used the multimodal neuroimaging method to explore the neural mechanism of major depression and subthreshold depression,and compare the different central mechanism of curative effect between acupuncture and medicine.The aim of the study is to uncover the characteristic of antidepressant mechanism in acupuncture,and provide a more objective and visible curative evidence.Objective1.Analyze the research status of registered clinical trial of acupuncture in treating depression,and probe the research method,directions and problems in the domestic and international study;organized and summarized the MRI articles in depression,to compare the characteristic between different neuroimaging methods and sum up the current results;summarized the current research status of MRI study in acupuncture antidepressant and explore the future research direction.2.Based on the multimodal neuroimaging method by using volumetric and functional analysis,the study compared the volumetric and functional difference between healthy people,subthreshold depression and major depression,to explore the correlation between structural and functional changes.3.Based on the multimodal neuroimaging method,we explore the feature of neural mechanism of acupuncture antidepressant in the individual level,and the discrepancy between different clinical therapies.Methods1.Evaluation on clinical research1.1 Registered clinical trial of acupuncture in treating depression Based on the sixteen registered trials on the International Clinical Trials Registry Platform(ICTRP),we used the "acupuncture" and "depression" as the key words to retrieve.There are 45 trials which met the searching conditions and were evaluated according to the characteristics of clinical interventions.1.2 Current status of MRI research in depression Based on the US National Library of Medicine National Institutes of Health(PubMed),we search the relevance articles of MRI researches in major depression and subthreshold depression.The key words of "depression" and "MRI" were used to retrieve the first time.The secondary retrieve was done through manual work,and the articles about volumetric and functional MRI researches on depression in cross-sectional or longitudinal study were involved.The secondary and combined with internal disease or other psychiatric disorders,like phobia,substance abuse and eating disorder,were excluded.The review,meta-analysis,protocol,theoretical discussion,letters and case report were also excluded from the final statistics.Depending on the inclusion and exclusion criteria,there are 845 articles to be evaluated in the study.1.3 Current research status of MRI study in acupuncture antidepressantBased on the CNKI database,all the articles about acupuncture antidepressant were retrieved.The key words of "depression" "Yu syndrome" and "Yu disease" were used for the first retrieve,and "acupuncture" was used for the secondary,including earpins,electronic acupuncture,abdominal needle,head needle,acupuncture and acupuncture medicine combined.Third,the "MRI" was used for the last key word to screen based on the results above.Review,mata-analysis,case report,theoretical discussion and abstract were excluded.There are 15 articles included based on the criteria above.2.Clinical research2.1 Multimodal neuroimaging research on major and subthreshold depression Based on the inclusion criteria,there are 14 mild to moderate depressive patients,15 subthreshold individuals and 15 healthy individuals were screened for the MRI.The structural(VBM)and functional(fALFF and ROI-based functional connectivity)were combined to explore the changing characteristics in different groups,and the correlation analysis between volumetric/functional changes and HAMD/QIDS scores were analyzed to explore the correlation between neural changes and clinical scales.2.2 MRI study in acupuncture antidepressantBased on the inclusion and exclusion criteria,the mild to moderate major depressive patients were randomized distributed into acupuncture + placebo,acupuncture + medicine and medicine + sham acupuncture groups to receive 8 weeks clinical intervention.The MRI screen and clinical assessment was provided before and after the intervention.By using the multimodal neuroimaging method,we are trying to explore the neural mechanism of curative effect between different interventions and the advantages of acupuncture antidepressant.Results 1.Evaluation on clinical researchThere are 45 registered clinical trials in domestic and international nations.The selection of the type of depression,diagnostic criteria,the usage of sham-acupuncture and the evaluation of acupuncture antidepressant are various.The application of acupuncture in treating depression is not mature in worldwide,and the standardization and evaluation of the specific curative effect of acupuncture antidepressant.There are 845 articles about MRI research in depression,68 of them focused on the high risk individuals,250 of them focused on the structural MRI,343 of them focused on the functional MRI research,28 of them focused on the multimodal neuroimaging methods,8 of them focused on the different disease severity and 137 of them focused on the different clinical interventions.Based on the multimodal,deep machine learning and connectomics methods,we can make big improvement in the clinical diagnostic and individualized treatment through transforming the neuroimaging to clinical application.MRI study in acupuncture antidepressant still at an initial stage.The integrated regulation of acupuncture in multiple targets can be measured in structural,functional and connectomic method,which could be the future research orientation in the therapeutic mechanism of acupuncture antidepressant.2.Clinical research2.1 Both the depressive and subthreshold depressive individuals showed the heterogeneity of volumetric and functional connectivity within frontal sub regions(lateral,medial and orbital)and between the sub regions and whole brain regions.It reflected the consistency in the different stages of disease development.2.2 The structural and functional alternations in subthreshold depressive individuals are relatively independent,but it is opposite in the depressive group.This condition reflected the characteristic changes between structural and functional alternation in the disease development process.2.3 We found the grey matter volume of frontal lobe,precuneus and cerebellar were correlated with the anxiety/somatization factor;the volume of precentral gyrus was correlated with somnipathy factor.Functional MRI showed a wide range of relevance between brain functional changes and the seven-factor in HAMD-24,which is more sensitive than volumetric alternation.The significant relevant regions are in the frontal lobe,parietal lobe,limbic lobe and temporal lobe.2.4 The neural mechanism of electro-acupuncture was mainly by regulating the volume of precentral gyrus,medial and inferior temporal lobe,and the functional connectivity of frontal,temporal and limbic regions.The alternation regions above are highlight the characteristics of electro-acupuncture in treating the somatization syndromes.Conclusion1.The integrated regulation of acupuncture in multiple targets with the measures of functional and structural MRI combined could be the future research orientation in the therapeutic mechanism of acupuncture antidepressant.2.The multimodal neuroimaging method of functional and structural combined,can reflect the neural mechanisms of depression comprehensively.3.The neural mechanism of electro-acupuncture antidepressant highlights the advantages of electro-acupuncture in improving somatization syndromes.