Skip to main content Accessibility help

Rhythmic low-field magnetic stimulation may improve depression by increasing brain-derived neurotrophic factor

  • Le Xiao (a1), Christoph U. Correll (a2), Lei Feng (a1), Yu-Tao Xiang (a3), Yuan Feng (a1), Chang-Qing Hu (a1), Rena Li (a1) (a4) and Gang Wang (a1)...



Low-field magnetic stimulation (LFMS) has mood-elevating effect, and the increase of brain-derived neurotrophic factor (BDNF) is associated with antidepressant treatment. We evaluated the effects and association with BDNF of rhythmic LFMS in the treatment of major depressive disorder (MDD).


A total of 22 MDD patients were randomized to rhythmic alpha stimulation (RAS) or rhythmic delta stimulation (RDS), with 5 sessions per week, lasting for 6 weeks. Outcomes assessments included the 17-item Hamilton Depression Rating Scale (HAMD–17), the Hamilton Anxiety Rating Scale (HAMA), and the Clinical Global Impressions–Severity scale (CGI–S) at baseline and at weeks 1, 2, 3, 4, and 6. Serum BDNF level was measured at baseline and at weeks 2, 4, and 6.


HAMD–17, HAMA, and CGI–S scores were significantly reduced with both RAS and RDS. RAS patients had numerically greater reductions in HAMD–17 scores than RDS patients (8.9 ± 7.4 vs. 6.2 ± 6.2, effect size [ES]=0.40), while RDS patients had greater improvement in HAMA scores (8.2 ± 8.0 vs. 5.3 ± 5.8, ES=0.42). RAS was associated with clinically relevant advantages in response (54.5% vs. 18.2%, number-needed-to-treat [NNT]=3) and remission (36.4% vs. 9.1%, NNT=4). BDNF increased significantly during the 6-week study period (p<0.05), with greater increases in RAS at weeks 4 and 6 (ES=0.66—0.76) and statistical superiority at week 2 (p=0.034, ES=1.23). Baseline BDNF in the 8 responders (24.8±9.0 ng/ml) was lower than in the 14 nonresponders (31.1±7.3 ng/ml, p=0.083, ES=–0.79), and BDNF increased more in responders (8.9±7.8 ng/ml) than in nonresponders (1.8±3.5 ng/ml, p=0.044). The change in BDNF at week 2 was the most strongly predicted response (p=0.016).


Rhythmic LFMS was effective for MDD. BDNF may moderate/mediate the efficacy of LFMS.


Corresponding author

*Address for correspondence: Dr. Gang Wang, Mood Disorders Center, Beijing Anding Hospital, No. 5 Ankang Lane, Deshengmenwai Avenue, Xicheng District, Beijing 100088, China. (Email:


Hide All

This study was funded by the Beijing Municipal Administration of Hospitals, Clinical Medicine Development of Special Funding Support no. ZYLX201403; by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support no ZYLX201607; by the Beijing Municipal Administration of Hospitals Incubating Program, Code no. PX2017048; by the National Key Technology Research and Development Program of the Ministry of Science and Technology of China grant no. 2015BAI13B03; and by the Beijing Municipal Administration of Hospitals’ Ascent Plan, Code no. DFL20151801.



Hide All
1. Rohan, M, Parow, A, Stoll, AL, Demopulos, C, et al. Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator. Am J Psychiatry. 2004; 161(1): 9398.
2. Rohan, ML, Yamamoto, RT, Ravichandran, CT, et al. Rapid mood-elevating effects of low field magnetic stimulation in depression. Biol Psychiatry. 2014; 76(3): 186193.
3. Carlezon, WA, Rohan, ML, Mague, SD, et al. Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats. Biol Psychiatry. 2005; 57(6): 571576.
4. Shafi, M, Stern, AP, Pascual-Leone, A. Adding low field magnetic stimulation to noninvasive electro-magnetic neuromodulatory therapies. Biol Psychiatry. 2014; 76(3): 170171.
5. Leuchter, AF, Cook, IA, Jin, Y, Phillips, B. The relationship between brain oscillatory activity and therapeutic effectiveness of transcranial magnetic stimulation in the treatment of major depressive disorder. Front Hum Neurosci. 2013; 7: 37.
6. Leuchter, AF, Cook, IA, Feifel, D, et al. Efficacy and safety of low-field synchronized transcranial magnetic stimulation (sTMS) for treatment of major depression. Brain Stimul. 2015; 8(4): 787794.
7. Kammer, T, Spitzer, M. Brain stimulation in psychiatry: methods and magnets, patients and parameters. Curr Opin Psychiatry. 2012; 25(6): 535t41.
8. Peng, DT, Zhu, R, Yuan, XR, Zhang, X. Clinical study of deep brain magnetic stimulation technique in the treatment of Alzheimer’s disease [in Chinese]. Chin J Geriatr. 2012; 31(11): 929931.
9. Zhang, Y, Mao, RR, Chen, ZF, et al. Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders. Mol Brain. 2014; 7: 11.
10. Garcia-Toro, M, Montes, JM, Talavera, JA. Functional cerebral asymmetry in affective disorders: new facts contributed by transcranial magnetic stimulation. J Affect Disord. 2001; 66(2–3): 103109.
11. Burt, T, Lisanby, SH, Sackeim, HA. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol. 2002; 5(01): 73103.
12. Gershon, AA, Dannon, PN, Grunhaus, L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003; 160(5): 835845.
13. Thut, G, Veniero, D, Romei, V, Miniussi, C, Schyns, P, Gross, J. Rhythmic TMS causes local entrainment of natural oscillatory signatures. Curr Biol. 2011; 21(14): 11761185.
14. Veniero, D, Brignani, D, Thut, G, Miniussi, C. Alpha-generation as basic response-signature to transcranial magnetic stimulation (TMS) targeting the human resting motor cortex: a TMS/EEG co-registration study. Psychophysiology. 2011; 48(10): 13811389.
15. Sadaghiani, S, Scheeringa, R, Lehongre, K, Morillon, B, Giraud, AL, Kleinschmidt, A. Intrinsic connectivity networks, alpha oscillations, and tonic alertness: a simultaneous electroencephalography/functional magnetic resonance imaging study. J Neurosci. 2010; 30(30): 1024310250.
16. Xiao, L, Feng, Y, Feng, L, Hu, C, Zhang, G, Wang, G. Effects of deep-brain magnetic stimulation on brain derived neurotrophic factor in treatment-resistant depression [in Chinese]. J Clin Psychiatry. 2015; 25(6): 361364.
17. Jin, Y, Phillips, B. A pilot study of the use of EEG-based synchronized transcranial magnetic stimulation (sTMS) for treatment of major depression. BMC Psychiatry. 2014; 14: 13.
18. Park, H, Poo, M. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci. 2013; 14(1): 723.
19. Groves, JO. Is it time to reassess the BDNF hypothesis of depression? Mol Psychiatry. 2007; 12(12): 10791088.
20. Adachi, M, Barrot, M, Autry, AE, Theobald, D, Monteggia, LM. Selective loss of brain-derived neurotrophic factor in the dentate gyrus attenuates antidepressant efficacy. Biol Psychiatry. 2008; 63(7): 642649.
21. Duman, RS, Monteggia, LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006; 59(12): 11161127.
22. Brunoni, AR, Lopes, M, Fregni, F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008; 11(8): 1169.
23. Sen, S, Duman, R, Sanacora, G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008; 64(6): 527532.
24. Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23: 5662.
25. Xie, GR, Shen, QJ. Use of the Chinese version of the Hamilton Rating Scale for Depression in general population and patients with major depression. Chin J Nerv Ment Dis. 1984; 10: 364.
26. Hamilton, M. The assessment of anxiety states by rating. Br J Psychiatry. 1959; 32(1): 5055.
27. Guy, W. Clinical global impressions. In. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: National Institute for Mental Health; 1976: 218222.
28. Trivedi, MH, Rush, AJ, Wisniewski, SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006; 163(1): 2840.
29. Greenhouse, SW, Geisser, S. On methods in the analysis of profile data. Psychometrika. 1959; 24(2): 95112.
30. Citrome, L. Number needed to treat: what it is and what it isn’t, and why every clinician should know how to calculate it. J Clin Psychiatry. 2011; 72(3): 412413.
31. Cohen, J. Statistical Power Analysis for the Behavioral Sciences, 2nd ed. Hillsdale, NJ: Erlbaum; 1988.
32. Pan, W, Banks, WA, Fasold, MB, Bluth, J, Kastin, AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998; 37(12): 15531561.
33. Sartorius, A, Hellweg, R, Litzke, J, et al. Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry. 2009; 42(6): 270276.
34. Wang, HY, Crupi, D, Liu, J, et al. Repetitive transcranial magnetic stimulation enhances BDNF–TrkB signaling in both brain and lymphocyte. J Neurosci. 2011; 31(30): 1104411054.
35. Yukimasa, T, Yoshimura, R, Tamagawa, A, et al. High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors. Pharmacopsychiatry. 2006; 39(2): 5259.
36. Zanardini, R, Gazzoli, A, Ventriglia, M, et al. Effect of repetitive transcranial magnetic stimulation on serum brain-derived neurotrophic factor in drug resistant depressed patients. J Affect Disord. 2006; 91(1): 8386.
37. Lang, C, Schüler, D. Biogenic nanoparticles: production, characterization, and application of bacterial magnetosomes. J Phys Condens Matter. 2006; 18(38): S2815S2828.
38. Gedge, L, Beaudoin, A, Lazowski, L, du Toit, R, Jokic, R, Milev, R. Effects of electroconvulsive therapy and repetitive transcranial magnetic stimulation on serum brain-derived neurotrophic factor levels in patients with depression. Front Psychiatry. 2012; 3: 12.
39. Angelucci, F, Oliviero, A, Pilato, F, et al. Transcranial magnetic stimulation and BDNF plasma levels in amyotrophic lateral sclerosis. Neuroreport. 2004; 15(4): 717720.
40. Rusovan, A, Kanje, M, Mild, KH. The stimulatory effect of magnetic fields on regeneration of the rat sciatic nerve is frequency dependent. Exp Neurol. 1992; 117(1): 8184.
41. Volkow, ND, Tomasi, D, Wang, GJ, et al. Effects of low-field magnetic stimulation on brain glucose metabolism. NeuroImage. 2010; 51(2): 623628.
42. Rokni-Yazdi, H, Sotoudeh, H, Akhondzadeh, S, Sotoudeh, E, Asadi, H, Shakiba, M. Antidepressant-like effect of magnetic resonance imaging-based stimulation in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(2): 503509.
43. Drevets, WC, Price, JL, Furey, ML. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct Funct. 2008; 213(1–2): 93118.
44. Leuchter, AF, Cook, IA, Hunter, AM, Cai, C, Horvath, S. Resting-state quantitative electroencephalography reveals increased neurophysiologic connectivity in depression. PLoS One. 2012; 7(2): e32508.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed