High frequency deep transcranial magnetic stimulation acutely increases β-endorphins in obese humans
In obesity, metabolic and voluntary factors regulate appetite, and a dysregulation of the reward pathway was demonstrated in all addiction disorders. Deep transcranial magnetic stimulation (dTMS) is already used to modulate cerebral dopamine activation in neuro-psychiatric diseases. We presently assess the acute effect of high frequency (HF) and low frequency (LF) dTMS on the modulation of the main neuropeptides and neurotransmitters involved in the reward pathway in obese subjects.
This study was designed as a double-blind, sham-controlled, randomized clinical trial. Thirty-three obese patients (9 males, 24 females, age 48.1 ± 10.6, BMI 36.4 ± 4.7) were enrolled in the study. All patients were studied during a single dTMS session and blood aliquots were drawn before and after a single dTMS session. Metabolic and neuro-endocrine parameters were evaluated before and after: (1) 18 Hz dTMS (HF, 13 patients); (2) 1 Hz dTMS (LF, 10 patients); (3) Sham treatment (Sham, 10 patients).
No statistically significant variations in metabolic parameters, systolic and diastolic blood pressure, and heart rate were shown acutely. HF showed a significant increase of β-endorphin compared to other groups (p = 0.048); a significant increase of ghrelin in LF (p = 0.041) was also demonstrated.
A single session of HF dTMS treatment determines in obese subjects an acute increase of β-endorphin level, indicating an activation of the reward pathway. The present findings constitute proof of principle for a potential application of this methodology in obesity treatment.
KeywordsObesity Transcranial magnetic stimulation Food craving β-endorphin Ghrelin
This study was supported by the Italian Ministry of Health (RF-2011–02349303).
Prof. Livio Luzi was a recipient of a grant from the Italian Ministry of Health (RF-2011–02349303).
LL and IT contributed to designing the research study. LL, AF, and CM conducted experiments; specifically, LL provided research conduct oversight; AF contributed to performing dTMS after a specific training, and to providing medical oversight; CM contributed to collecting blood samples. AF and MA contributed to acquiring data; FA and VM performed statistical analysis. AF, LL, MA, FA and VM contributed to writing the manuscript. As corresponding author, LL confirms that he had full access to all the data in the study and has final responsibility for the decision to submit for publication.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.D. Val-Laillet, E. Aarts, B. Weber, M. Ferrari, V. Quaresima, L.E. Stoeckel, M. Alonso-Alonso, M. Audette, C.H. Malbert, E. Stice, Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity. Neuroimage Clin. 8, 1–31 (2015)CrossRefGoogle Scholar
- 5.N.D. Volkow, G.J. Wang, F. Telang, J.S. Fowler, P.K. Thanos, J. Logan, D. Alexoff, Y.S. Ding, C. Wong, Y. Ma, K. Pradhan, Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage 42(4), 1537–1543 (2008)CrossRefGoogle Scholar
- 18.G. Addolorato, M. Antonelli, F. Cocciolillo, G.A. Vassallo, C. Tarli, L. Sestito, A. Mirijello, A. Ferrulli, D.A. Pizzuto, G. Camardese, A. Miceli, M. Diana, A. Giordano, A. Gasbarrini, D. Di Giuda, Deep transcranial magnetic stimulation of the dorsolateral prefrontal cortex in alcohol use disorder patients: effects on dopamine transporter availability and alcohol intake. Eur. Neuropsychopharmacol. 27(5), 450–461 (2017)CrossRefGoogle Scholar
- 19.L. Dinur-Klein, P. Dannon, A. Hadar, O. Rosenberg, Y. Roth, M. Kotler, A. Zangen, Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial. Biol. Psychiatry 76(9), 742–749 (2014)CrossRefGoogle Scholar
- 22.C. Rapinesi, A. Del Casale, P. Scatena, G.D. Kotzalidis, S. Di Pietro, V.R. Ferri, F.S. Bersani, R. Brugnoli, R.N. Raccah, A. Zangen, S. Ferracuti, F. Orzi, P. Girardi, G. Sette, Add-on deep Transcranial Magnetic Stimulation (dTMS) for the treatment of chronic migraine: a preliminary study. Neurosci. Lett. 623, 7–12 (2016)CrossRefGoogle Scholar
- 23.E. Yates, G. Balu, Deep Transcranial Magnetic Stimulation: A Promising Drug-Free Treatment Modality in the Treatment of Chronic Low Back Pain. Del. Med. J. 88(3), 90–92 (2016)Google Scholar
- 24.M.B. First, R.L. Spitzer, M. Gibbon, J.B. Williams,: Structured clinical interview for DSM-IV-TR axis I disorders, research version, non-patient edition (SCID-I/NP). New York, New York, USA: Biometrics Research, New York State Psychiatric Institute (2002)Google Scholar
- 27.M.F. Maranhão, N.M. Estella, M.E. Cury, V.L. Amigo, C.M. Picasso, A. Berberian, I. Campbell, U. Schmidt, A.M. Claudino, The effects of repetitive transcranial magnetic stimulation in obese females with binge eating disorder: a protocol for a double-blinded, randomized, sham-controlled trial. BMC Psychiatry 15, 194 (2015)CrossRefGoogle Scholar
- 29.C. Gianoulakis, Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. J. Psychiatry Neurosci. 26(4), 304–318 (2001)Google Scholar
- 31.K. Blum, E.R. Braverman, J.M. Holder, J.F. Lubar, V.J. Monastra, D. Miller, J.O. Lubar, T.J. Chen, D.E. Comings, Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. J. Psychoact. Drugs 32(Suppl:i-iv), 1–112 (2000)CrossRefGoogle Scholar
- 33.X. Li, R.J. Malcolm, K. Huebner, C.A. Hanlon, J.J. Taylor, K.T. Brady, M.S. George, R.E. See, Low frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex transiently increases cue-induced craving for methamphetamine: a preliminary study. Drug Alcohol. Depend. 133(2), 641–646 (2013)CrossRefGoogle Scholar