title: Imaging the serotonin 1A receptor using [11C]WAY100635 in healthy controls and major depression.
abstract: As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the 1A receptor (5-HT(1A)) has been implicated in depression and suicide. Using the [carbonyl-(11)C]WAY100635 ([(11)C]WAY) ligand and positron emission tomography, we have studied the 5-HT(1A) receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT(1A) binding potential (BP(F)) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP(F) in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BP(F) in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT(1A) BP(F) may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT(1A) imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [(11)C]CUMI-101 agonist tracer.
authors: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY 10043, USA.
authors: Natalie
authors: N
authors: Hesselgrave
authors: Ramin V
authors: RV
authors: Parsey
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000737:chemistry; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008024:Ligands; D010879:Piperazines / Q000737:chemistry*; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography / Q000379:methods*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry*; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry* / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D015415:Biomarkers; D008024:Ligands; D010879:Piperazines; D011725:Pyridines; C112544:desmethyl-WAY 100635; D044282:Receptor, Serotonin, 5-HT1A