Effects of bilateral sequential theta-burst stimulation on 5-HT_1A receptors on dorsolateral prefrontal cortex in treatment resistant depression

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-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 in 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 5-HT1A receptor specific binding VS. While post-hoc comparisons showed no significant changes of 5-HT1A VS in either group, higher 5-HT1A VS after treatment correlated with greater difference in HAMD (r=-0.62), indicative of potential effects of TBS on the 5-HT1A receptor. Due to the small sample size, all results, however, must be regarded with caution.