Chinese Journal of Integrative Medicine

, Volume 17, Issue 3, pp 190–199 | Cite as

The relevance between symptoms and magnetic resonance imaging analysis of the hippocampus of depressed patients given electro-acupuncture combined with Fluoxetine intervention — A randomized, controlled trial

  • Dong-mei Duan (段冬梅)Email author
  • Ya Tu (图 娅)
  • Shuang Jiao (焦 爽)
  • Wen Qin (秦 文)
Original Article



To probe the relevance between depressive symptoms and hippocampal volume and its metabolites detected by magnetic resonance imaging (MRI) in depressed patients who were given electro-acupuncture (EA) combined with Fluoxetine before and after treatment.


A randomized, controlled trial was conducted. A total of 75 cases of mild or moderate depression were randomly assigned to two groups: the EA group which received EA combined with Fluoxetine; the Fluoxetine group which received Fluoxetine only as the control. The 17-item Hamilton Scale for Depression (HAMD) was used to assess the depression level. The relevance between the changes of the hippocampal volume and its metabolites, including N-acetyl aspartate (NAA)/creatine (Cr) and choline containing compounds (Cho)/Cr, and the reduction rate of the HAMD score before and after treatment of the two groups were analyzed.


At the end of the treatment, the therapeutic response rates were not statistically different between the two groups (73.53% for the Fluoxetine group and 83.33% for the EA group, respectively). Compared to that of the Fluoxetine group, a significant difference was shown in the EA group in the reduction rate of the HAMD scores (P<0.05). There was a negative correlation between the therapeutic effect and the HAMD scores before treatment in both groups of patients. There was no significant difference in the hippocampal volume before and after treatment. The NAA/Cr ratio of both groups increased after treatment, with the EA group increasing more. There was a negative correlation between the rate of change of the NAA/Cr after treatment and the HAMD scores before treatment in the two groups. In the Fluoxetine group, the Cho/Cr ratio showed no significant difference before and after treatment, which had no relevance with the HAMD scores before treatment either. Meanwhile, in the EA group, the Cho/Cr ratio showed a significant difference before and after treatment, which also had a positive relevance with the HAMD scores before treatment.


There was a significant improvement in the hippocampal metabolites in depressed patients who treated by EA combined with Fluoxetine. Those differences showed relevance with the HAMD scores before treatment.


depression electro-acupuncture hippocampus magnetic resonance imaging Fluoxetine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Simon GE, Barber C, Birnbaum HG, Frank RG, Greenberg PE, Rose RM, et al. Depression and work productivity: the comparative costs of treatment versus nontreatment. J Occup Environ Med 2001;43:2–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Kessler RC, Soukup J, Davis RB, Foster Df, Wilkey SA, Van Rompay MI, et al. The use of complementary and alternative therapies to treat anxiety and depression in the United States. Am J Psychiatry 2001;158:289–294.PubMedCrossRefGoogle Scholar
  3. 3.
    Kato T, Inubushi T, Kato N. Magnetic resonance spectroscopy in affective disorders. J Neuropsychiatry Clin Neurosci 1998;10:133–147.PubMedGoogle Scholar
  4. 4.
    Axelson DA, Doraiswamy PM, McDonald WM, Boyko OB, Tupler LA, Patterson LJ, et al. Hypercortisolemia and hippocampal changes in depression. Psychiatry Res 1993;47:163–173.PubMedCrossRefGoogle Scholar
  5. 5.
    Campbell S, Maqueen G. The role of the hippocampus in the pathophysiology of major depression. Psychiatry Neurosci 2004;29: 417–426.Google Scholar
  6. 6.
    Hashimoto K, Shimizu E, Lyo M. Critical role of brainderived neurotrophic factor in mood disorders. Brain Res Rev 2004;45:104–114.PubMedCrossRefGoogle Scholar
  7. 7.
    Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA. Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiatry 2005;57:21–26.PubMedCrossRefGoogle Scholar
  8. 8.
    Howell LL, Wilcox KM. Functional imaging and neurochemical correlates of stimulant self administration in primates. Psychopharmacology 2002:163:352–361.PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang JB, Wang LL, Lu M, Liu LY. Li D. Effects of acupuncture at different acupoints on behaviors in depression model rats. Chin Acupunct Moxibust (Chin) 2005;25:639–643.Google Scholar
  10. 10.
    Wu MT, Hsieh JC, Xiong J, Yang CF, Pan HB, Chen YC, et al. Central nervous pathway for acupuncture stimulation:localization of processing with functional MR imaging of the brain-preliminary experience. Radiology 1999;212:133–141.PubMedGoogle Scholar
  11. 11.
    Lu J, Shi YJ, Jin ZX, Tu Y. Comparative study of the antidepressive effects of electroacupuncture on different frequencies in the rats. J Beijing Univ Tradit Chin Med (Chin) 2003;26(6):83–84.Google Scholar
  12. 12.
    Semple D, Smyth R, Darjee R, eds. Oxford handbook of psychiatry. Beijing: People’s Medical Publishing House; 2006:22–25.Google Scholar
  13. 13.
    Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.PubMedCrossRefGoogle Scholar
  14. 14.
    Sala M, Perez J, Soloff P, Ucelli di Nemi S, Caverzasi E, Soares JC, et al. Stress and hippocampal abnormalities in psychiatric disorders. Eur Neuropsychopharmacol 2004;14:393–405.PubMedCrossRefGoogle Scholar
  15. 15.
    Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M, et al. Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry 2002;159:1112–1118.PubMedCrossRefGoogle Scholar
  16. 16.
    Shen J, Rothman DL. Magnetic resonance spectroscopic approaches to studying neuronal: Glial interactions. Biol Psychiatry 2002;52:694–700.PubMedCrossRefGoogle Scholar
  17. 17.
    Frodl T, Schaub A, Banac S, Charypar M, Jager M, Kummler P, et al. Reduced hippocampal volume correlates with executive dysfunctioning in major depression. J Psychiatry Neurosci 2006;31:316–325.PubMedGoogle Scholar
  18. 18.
    Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW. Hippocampal atrophy in recurrent major depression. Proc Natl Acad USA 1996;93:3908–3913.CrossRefGoogle Scholar
  19. 19.
    Campbell S, Marriott M, Nahmias C, MacQueen GM. Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 2004;161:598–607.PubMedCrossRefGoogle Scholar
  20. 20.
    Stoll AL, Renshaw PF, Yurgelun-Todd DA, Cohen BM. Neuroimaging in bipolar disorder: what have we learned? Biol Psychiatry 2000;48:505–517.PubMedCrossRefGoogle Scholar
  21. 21.
    Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry 2002;159:2072–2080.PubMedCrossRefGoogle Scholar
  22. 22.
    Lloyd AJ, Ferrier IN, Barber R, Gholkar A, Young AH, O’Brien JT. Hippocampal volume change in depression: late-and early-onset illness compared. Br J Psychiatry 2004;184:488–495.PubMedCrossRefGoogle Scholar
  23. 23.
    Colla M, Kronenberg C, Deuschle M, Meichel K, Hagen T, Bohrer M, et al. Hippocampal volume reduction and HPA-system activity in major depression. J Psychiatr Res 2007;41:553–560.PubMedCrossRefGoogle Scholar
  24. 24.
    Bell-McGinty S, Butters MA, Meltzer CC, Greer PJ, Reynolds CF 3rd, Becker JT. Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration. Am J Psychiatry 2002;159:1424–1427.PubMedCrossRefGoogle Scholar
  25. 25.
    Shelline YI, Gado MH, Kraemer HC. Untreated depression and hippocampal volume loss. Am J Psychiatry 2003;160:1516–1518.CrossRefGoogle Scholar
  26. 26.
    Yue Q, Isobe T, Shibata Y, Anno I, Kawamura H, Yamamoto Y, et al. New observations concerning the interpretation of magnetic resonance spectroscopy of meningioma. Eur Radiol 2008;18:2901–2911.PubMedCrossRefGoogle Scholar
  27. 27.
    Mervaala E, Fohr J, Kononen M, Valkonen-Korhonen M, Vainio P, Partanen K, et al. Quantitative MRI of the hippocampus and amygdale in severe depression. Psychol Med 2000;30:117–125.PubMedCrossRefGoogle Scholar
  28. 28.
    Lucassen PJ, Fuchs E, Czch B. Antidepressant treatment with tianeptine reduces apoptosis in hippocampal dentate gyrus and temporal cortex. Biol Psychiatry 2004;55:789–796.PubMedCrossRefGoogle Scholar
  29. 29.
    Rajkowska G. Depression: what we can learn from postmortem studies. Neuroscientist 2003;4:273–284.CrossRefGoogle Scholar
  30. 30.
    Duman RS, Malberg J, Nakagawa S, D’sa C. Neuronal plasticity and survival in mood disorders. Biol Psychiatry 2000;48:732–739.PubMedCrossRefGoogle Scholar
  31. 31.
    Magarinos AM, McEwen B, Flugge G, Fuchs E. Chronic psychosocial stress causes apical dendritic atrophy of hippocampal CA3 pyramidal neurons in subordinate tree shrews. J Neurosci 1996;15:3534–3540.Google Scholar
  32. 32.
    Cze’h B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, et al. Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 2001;98:12796–12801.CrossRefGoogle Scholar
  33. 33.
    Moore GJ, Galloway MP. Magnetic resonance spectroscopy: neurochemistry and treatment effects in affective disorders. Psychopharmacol Bull 2002;36:5–23.PubMedGoogle Scholar
  34. 34.
    Jernigan TL, Archibald SL, Berhow MT, Soweel ER, Foster DS, Hesselink JR. Cerebral structure on MRI, Part I: Localization of age-related changes. Biol Psychiatry 1991;29:55–67.PubMedCrossRefGoogle Scholar
  35. 35.
    Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, et al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry 2000;47:1087–1090.PubMedCrossRefGoogle Scholar
  36. 36.
    Kato T, Inubushi T, Kato N. Magnetic resonance spectroscopy in affective disorders. J Neurop Psychiatry Clin Neurosci 1998;10:133–147.Google Scholar
  37. 37.
    Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386:824–827.PubMedCrossRefGoogle Scholar
  38. 38.
    Magaris AM, Deslandes A, Mcewen BS. Effect of antidepressant and benzodiazepine trentments on the dendritic structure of CA3 pyrimidal neurons after chronic stress. Eur J Pharmacol 1999;371:113–122.CrossRefGoogle Scholar
  39. 39.
    Rajkowska G. Cell pathology in bipolar disorder. Bipolar Disord 2002;4:105–116.PubMedCrossRefGoogle Scholar
  40. 40.
    Fayed N, Modrego PJ. The contribution of magnetic resonance spectroscopy and echoplanar perfusionweighted MRI in the initial assessment of brain tumours. J Neurooncol 2005;72:261–265.PubMedCrossRefGoogle Scholar
  41. 41.
    Sapolsky RM. The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death. Biol Psychiatry 2000;48:755–765.PubMedCrossRefGoogle Scholar
  42. 42.
    Sabatier J, Gilard V, Malet-Martino M, Ranjeva JP, Terral C, Breil S, et al. Characterisation of choline compounds with in vitro 1H magnetic resonance spectroscopy for discrimination of primary brain tumours. Invest Radiol 1999;34:230–235.PubMedCrossRefGoogle Scholar
  43. 43.
    Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. The hippocampus in patients treated with electroconvulsive therapy: a protonmagnetic resonance spectroscopic imaging study. Arch Gen Psychiatry 2000;57:937–943.PubMedCrossRefGoogle Scholar
  44. 44.
    Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS. Hippocampal volume reduction in major depression. Am J Psychiatry 2000; 157:115–118.PubMedCrossRefGoogle Scholar
  45. 45.
    Brooks WM, Friedman SD, Stidley CA. Reproducibility of 1H-MRS in vivo. Magn Reson Med 1999;41:193–197.PubMedCrossRefGoogle Scholar
  46. 46.
    Miller BL. A review of chemical issues in 1HNMR spectroscopy: acetylaspartate, creatine and choline. NMR Bio Med 1991;4:47–52.CrossRefGoogle Scholar
  47. 47.
    Sapolsky RM. Stress, the aging brain, and the Mechanisms of Neuron Death. Cambridge, MA: MIT Press; 1992.Google Scholar
  48. 48.
    Pouwels PJ, Frahm J. Regional metabolite concentrations in human brain as determined by quantitative localized proton MRS. Magn Reson Med 1998;39:53–60.PubMedCrossRefGoogle Scholar

Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine and Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Dong-mei Duan (段冬梅)
    • 1
    Email author
  • Ya Tu (图 娅)
    • 2
  • Shuang Jiao (焦 爽)
    • 3
  • Wen Qin (秦 文)
    • 4
  1. 1.Department of Traditional Chinese Medicine of South BuildingChinese PLA General HospitalBeijingChina
  2. 2.Department of AcupunctureBeijing University of Chinese MedicineBeijingChina
  3. 3.Department of RehabilitationBeijing Friendship Hospital Affiliated to Capital Medical UniversityBeijingChina
  4. 4.Department of RadiologyBeijing Xuanwu Hospital Affi liated to Capital Medical UniversityBeijingChina

Personalised recommendations