Effects of bilateral sequential theta-burst stimulation on 5-HT_1A receptors in the dorsolateral prefrontal cortex in treatment-resistant depression: a proof-of-concept trial

Author(s)

Matej Murgaš, Jakob Unterholzner, Peter Stöhrmann, Cécile Philippe, Godber M. Godbersen, Lukas Nics, Murray B. Reed, Chrysoula Vraka, Thomas Vanicek, Wolfgang Wadsak, Georg S. Kranz, Andreas Hahn, Markus Mitterhauser, Marcus Hacker, Siegfried Kasper, Rupert Lanzenberger

Abstract

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-HT_1A) 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 (V_S) of 5-HT_1A receptor. While post-hoc comparisons showed no significant changes of 5-HT_1A receptor V_S in either group, higher 5-HT_1A receptor V_S 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-HT_1A receptor. Due to the small sample size, all results must, however, be regarded with caution.

Organisation(s)

Department of Inorganic Chemistry

External organisation(s)

Medizinische Universität Wien, Hong Kong Polytechnic University, Ludwig Boltzmann Intitute Applied Diagnostics

Journal

Translational Psychiatry

Volume

13

ISSN

2158-3188

DOI

https://doi.org/10.1038/s41398-023-02319-3

Publication date

12-2023

Peer reviewed

Yes

Austrian Fields of Science 2012

302065 Clinical psychiatry, 301210 Psychopharmacology

ASJC Scopus subject areas

Psychiatry and Mental health, Cellular and Molecular Neuroscience, Biological Psychiatry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/649e80f0-c27b-48fd-b5ac-2e888cbdaf46