title: 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-HT(1A)) in the mode of action of antidepressant treatment. This includes associations between treatment response and changes in 5-HT(1A) function and density by antidepressants. Further, alterations of the 5-HT(1A) receptor are consistently reported in depression. To elucidate the effect of ECT on 5-HT(1A) receptor binding, 12 subjects with severe treatment-resistant major depression underwent three positron emission tomography (PET) measurements using the highly selective radioligand [carbonyl-(11)C]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-HT(1A) receptor binding (BP(ND)) 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-HT(1A) receptor binding in the effect of ECT.
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. rupert.lanzenberger@meduniwien.ac.at
authors: R
authors: R
authors: Lanzenberger
authors: P
authors: P
authors: Baldinger
authors: A
authors: A
authors: Hahn
authors: J
authors: J
authors: Ungersboeck
authors: M
authors: M
authors: Mitterhauser
authors: D
authors: D
authors: Winkler
authors: Z
authors: Z
authors: Micskei
authors: P
authors: P
authors: Stein
authors: G
authors: G
authors: Karanikas
authors: W
authors: W
authors: Wadsak
authors: S
authors: S
authors: Kasper
authors: R
authors: R
authors: Frey
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000628:therapy*; D004565:Electroconvulsive Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000493:pharmacokinetics; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002247:Carbon Isotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide