TY - JOUR
T1 - Effects of bilateral sequential theta-burst stimulation on 5-HT1A receptors in the dorsolateral prefrontal cortex in treatment-resistant depression
T2 - a proof-of-concept trial
AU - Murgaš, Matej
AU - Unterholzner, Jakob
AU - Stöhrmann, Peter
AU - Philippe, Cécile
AU - Godbersen, Godber M.
AU - Nics, Lukas
AU - Reed, Murray B.
AU - Vraka, Chrysoula
AU - Vanicek, Thomas
AU - Wadsak, Wolfgang
AU - Kranz, Georg S.
AU - Hahn, Andreas
AU - Mitterhauser, Markus
AU - Hacker, Marcus
AU - Kasper, Siegfried
AU - Lanzenberger, Rupert
AU - Baldinger-Melich, Pia
N1 - Funding Information:
In the past three years SK has received grant/research support from Lundbeck; he has served as a consultant or on advisory boards for Angelini, Biogen, Esai, Janssen, IQVIA, Lundbeck, Mylan, Recordati, Sage and Schwabe; and he has served on speaker bureaus for Abbott, Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Lundbeck, Recordati, Sage, Sanofi, Schwabe, Servier, Sun Pharma and Vifor. Without any relevance to this work, RL declares that he received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR and Heel, and has served as a consultant for Ono Pharmaceutical. He received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. GSK declares that he received conference speaker honorarium from Roche, AOP Orphan and Pfizer. TV has served on speaker bureaus for Janssen. Without relevance to this work, WW received within the last 3 years research grants from ITM Medical Isotopes GmbH (Munich, Germany) and Scintomics (Fürstenfeldbruck, Germany). He is a part-time employee of CBmed GmbH (Graz, Austria) and a co-founder of MINUTE medical GmbH (Vienna, Austria). Without relevance to this work, MM is scientific advisor for ROTOP Pharma GmbH. The other authors do not report any conflict of interest.
Funding Information:
This research was funded in whole, or in part, by the Austrian Science Fund (FWF) [Grant number KLI 551, PI: S. Kasper]. MMu is funded by the Austrian Science Fund (FWF) [Grant number DOC 33-B27, Supervisor R. Lanzenberger]. MBR is a recipient of a DOC fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy, Medical University of Vienna. We would like to express our gratitude towards Jonathan Downar for his assistance in the conceptualization of the study. We would further like to thank Gregor Gryglewski, Marius Hienert, Marie Spies, Christoph Kraus, Alexander Kautzky, Arkadiusz Komorowski, Paul Michenthaler, and Richard Frey for clinical support, and Lucas Rischka and Sebastian Ganger for technical support, and all additional staff and students from the Neuroimaging Lab (NIL) involved in the realization of this research. Moreover, we would like to thank radiotechnologists, Ingrid Leitinger, and Harald Ibeschitz, for operating PET. Preliminary findings of this study were submitted as a poster to the 33rd CINP Hybrid World Congress of Neuropsychopharmacology. The present manuscript represents an updated version of the article “Effects of bilateral sequential theta-burst stimulation on 5-HT1A receptors on dorsolateral prefrontal cortex in treatment resistant depression” published on the preprint server medRxiv (https://www.medrxiv.org/content/10.1101/2022.02.18.22271165v1).
Funding Information:
This research was funded in whole, or in part, by the Austrian Science Fund (FWF) [Grant number KLI 551, PI: S. Kasper]. MMu is funded by the Austrian Science Fund (FWF) [Grant number DOC 33-B27, Supervisor R. Lanzenberger]. MBR is a recipient of a DOC fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy, Medical University of Vienna. We would like to express our gratitude towards Jonathan Downar for his assistance in the conceptualization of the study. We would further like to thank Gregor Gryglewski, Marius Hienert, Marie Spies, Christoph Kraus, Alexander Kautzky, Arkadiusz Komorowski, Paul Michenthaler, and Richard Frey for clinical support, and Lucas Rischka and Sebastian Ganger for technical support, and all additional staff and students from the Neuroimaging Lab (NIL) involved in the realization of this research. Moreover, we would like to thank radiotechnologists, Ingrid Leitinger, and Harald Ibeschitz, for operating PET. Preliminary findings of this study were submitted as a poster to the 33rd CINP Hybrid World Congress of Neuropsychopharmacology. The present manuscript represents an updated version of the article “Effects of bilateral sequential theta-burst stimulation on 5-HT receptors on dorsolateral prefrontal cortex in treatment resistant depression” published on the preprint server medRxiv ( https://www.medrxiv.org/content/10.1101/2022.02.18.22271165v1 ). 1A
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Theta-burst stimulation (TBS) represents a brain stimulation technique effective for treatment-resistant depression (TRD) as underlined by meta-analyses. While the methodology undergoes constant refinement, bilateral stimulation of the dorsolateral prefrontal cortex (DLPFC) appears promising to restore left DLPFC hypoactivity and right hyperactivity found in depression. The post-synaptic inhibitory serotonin-1A (5-HT1A) receptor, also occurring in the DLPFC, might be involved in this mechanism of action. To test this hypothesis, we performed PET-imaging using the tracer [carbonyl-11C]WAY-100635 including arterial blood sampling before and after a three-week treatment with TBS in 11 TRD patients compared to sham stimulation (n = 8 and n = 3, respectively). Treatment groups were randomly assigned, and TBS protocol consisted of excitatory intermittent TBS to the left and inhibitory continuous TBS to the right DLPFC. A linear mixed model including group, hemisphere, time, and Hamilton Rating Scale for Depression (HAMD) score revealed a 3-way interaction effect of group, time, and HAMD on specific distribution volume (VS) of 5-HT1A receptor. While post-hoc comparisons showed no significant changes of 5-HT1A receptor VS in either group, higher 5-HT1A receptor VS after treatment correlated with greater difference in HAMD (r = −0.62). The results of this proof-of-concept trial hint towards potential effects of TBS on the distribution of the 5-HT1A receptor. Due to the small sample size, all results must, however, be regarded with caution.
AB - Theta-burst stimulation (TBS) represents a brain stimulation technique effective for treatment-resistant depression (TRD) as underlined by meta-analyses. While the methodology undergoes constant refinement, bilateral stimulation of the dorsolateral prefrontal cortex (DLPFC) appears promising to restore left DLPFC hypoactivity and right hyperactivity found in depression. The post-synaptic inhibitory serotonin-1A (5-HT1A) receptor, also occurring in the DLPFC, might be involved in this mechanism of action. To test this hypothesis, we performed PET-imaging using the tracer [carbonyl-11C]WAY-100635 including arterial blood sampling before and after a three-week treatment with TBS in 11 TRD patients compared to sham stimulation (n = 8 and n = 3, respectively). Treatment groups were randomly assigned, and TBS protocol consisted of excitatory intermittent TBS to the left and inhibitory continuous TBS to the right DLPFC. A linear mixed model including group, hemisphere, time, and Hamilton Rating Scale for Depression (HAMD) score revealed a 3-way interaction effect of group, time, and HAMD on specific distribution volume (VS) of 5-HT1A receptor. While post-hoc comparisons showed no significant changes of 5-HT1A receptor VS in either group, higher 5-HT1A receptor VS after treatment correlated with greater difference in HAMD (r = −0.62). The results of this proof-of-concept trial hint towards potential effects of TBS on the distribution of the 5-HT1A receptor. Due to the small sample size, all results must, however, be regarded with caution.
UR - https://www.scopus.com/pages/publications/85147235480
U2 - 10.1038/s41398-023-02319-3
DO - 10.1038/s41398-023-02319-3
M3 - Journal article
C2 - 36725835
AN - SCOPUS:85147235480
SN - 2158-3188
VL - 13
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 33
ER -
SDG 3 Good Health and Well-being