Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET

Abstract

Electroconvulsive therapy (ECT) is a potent therapy in severe treatment-refractory depression. Although commonly applied in psychiatric clinical routine since decades, the exact neurobiological mechanism regarding its efficacy remains unclear. Results from preclinical and clinical studies emphasize a crucial involvement of the serotonin-1A receptor (5-HT1A) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT1A function and density by antidepressants. Further, alterations of the 5-HT1A receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT1A receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-11C]WAY100635, twice before (test–retest variability) and once after 10.08±2.35 ECT sessions. Ten patients (∼83%) were responders to ECT. The voxel-wise comparison of the 5-HT1A receptor binding (BPND) before and after ECT revealed a widespread reduction in cortical and subcortical regions (P<0.05 corrected), except for the occipital cortex and the cerebellum. Strongest reductions were found in regions consistently reported to be altered in major depression and involved in emotion regulation, such as the subgenual part of the anterior cingulate cortex (−27.5%), the orbitofrontal cortex (−30.1%), the amygdala (−31.8%), the hippocampus (−30.6%) and the insula (−28.9%). No significant change was found in the raphe nuclei. There was no significant difference in receptor binding in any region comparing the first two PET scans conducted before ECT. This PET study proposes a global involvement of the postsynaptic 5-HT1A receptor binding in the effect of ECT.

Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

“…Our result confirms the spatial distribution of the ECT effect in that regions subjected to the highest electric field strengths show the most structural change. The demonstrated anatomical pattern of local GMV changes largely overlaps the findings of ECT-induced decreases in serotonin receptor binding (19). However, our ECT patient cohort shows a prefrontal cortical GMV decrease in comparison with no-ECT patients, yet not to controls.…”

Major Depressive Disorder and Alterations in Insular Cortical Activity: A Review of Current Functional Magnetic Imaging Research

“…There is also increasing evidence that 5-HT activates neurotrophic factor activity in various brain regions, that seems to be decreased in response to stressors and in depression (Duman et al, 1999). In fact, reductions in serotonin receptor binding in the insula among other regions have been found in individuals suffering from social anxiety disorder (Lanzenberger et al, 2012), which may explain anxious and depressive-like symptoms in this population. Conversely, Cannon et al (2007) showed increased binding potential of the serotonin transporter in the insula, thalamus, and striatum of both bipolar and depressive populations compared to healthy controls.…”

Transient Serotonin Toxicity Evoked by Combination of Electroconvulsive Therapy and Fluoxetine

“…ECT seems to have significant effect on serotonin systems of the brain [5]. It is therefore conceivable that ECT combined with serotonin active drugs could be able to induce serotonin toxicity possibly in the form of serotonin syndrome.…”