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Abstract
Repetitive transcranial magnetic stimulation (rTMS) is an effective and well tolerable biological intervention in major depressive disorder (MDD) contributing to rapid symptom improvement. Molecular mechanisms underpinning the therapeutic effects of rTMS have still not been clarified. Recently published animal data implicated relevant associations with changes in endocannabinoid (eCB) brain levels during rTMS treatment, human studies, however, have not been published. In our study we assessed the detailed phenotypic spectrum of MDD and serum 2-arachidnoylglycerol (2-AG) and anandamide (AEA) levels in 18 patients with treatment-resistant depression before, immediately following, and two weeks after completion of a 10-day rTMS treatment. We found significant associations between serum 2-AG level changes from pretreatment to 2 weeks after treatment and symptom reduction. The greater the increase of 2-AG levels, the greater the improvement of depressive (p = 0.031), anxious (p = 0.007) and anhedonia symptoms (p = 0.047). Here we report for the first time a significant association of human circulating eCB and antidepressant effect of rTMS. Our data may indicate that direct stimulation of targeted brain areas can rapidly alleviate depressive complaints via activation of the eCB system.
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1 Nyírő Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary; Semmelweis University, Janos Szentagothai Doctoral School of Neuroscience, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821)
2 Semmelweis University, Janos Szentagothai Doctoral School of Neuroscience, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821); Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821)
3 Nyírő Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary (GRID:grid.11804.3c); Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821)
4 Semmelweis University, Department of Psychiatry and Psychotherapy, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821)
5 Nyírő Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary (GRID:grid.11804.3c); Semmelweis University, Janos Szentagothai Doctoral School of Neuroscience, Budapest, Hungary (GRID:grid.11804.3c) (ISNI:0000 0001 0942 9821)
6 Budapest University of Technology and Economics, Department of Inonrganic and Analytical Chemistry, Faculty of Chemical Technology and Biotechnology, Budapest, Hungary (GRID:grid.6759.d) (ISNI:0000 0001 2180 0451)