title: Elevated serotonin 1A binding in remitted major depressive disorder: evidence for a trait biological abnormality.
abstract: Several biological abnormalities in major depressive disorder (MDD) persist during episode remission, including altered serotonin neurotransmission, and may reflect underlying pathophysiology. We previously described elevated brain serotonin 1A (5-HT(1A)) receptor binding in antidepressant-naive (AN) subjects with MDD within a major depressive episode (MDE) compared with that in healthy controls using positron emission tomography (PET). In this study, we measured 5-HT(1A) receptor binding in unmedicated subjects with MDD during sustained remission, hypothesizing higher binding compared with that in healthy controls, and binding comparable with currently depressed AN subjects, indicative of a biological trait. We compared 5-HT(1A) binding potential (BP(F)) assessed through PET scanning with [(11)C]WAY-100635 in 15 subjects with recurrent MDD in remission for >or=12 months and off antidepressant medication for >or=6 months, 51 healthy controls, and 13 AN MDD subjects in a current MDE. Metabolite-corrected arterial input functions were acquired for the estimation of BP(F). Remitted depressed subjects had higher 5-HT(1A) BP(F) compared with healthy controls; this group difference did not vary significantly in magnitude across brain regions. 5-HT(1A) BP(F) was comparable in remitted and currently depressed subjects. Elevated 5-HT(1A) BP(F) level among subjects with remitted MDD appears to be a trait abnormality in MDD, which may underlie recurrent MDEs. Future studies should evaluate the role of genetic and environmental factors in producing elevated 5-HT(1A) BP(F) and MDD, and should examine whether 5-HT(1A) BP(F) is a vulnerability factor to MDEs that could have a role in screening high-risk populations for MDD.
authors.affiliation: Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University, New York, NY 10033, USA. jm2233@columbia.edu
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Miller
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Brennan
authors.forename: Todd R
authors.initials: TR
authors.lastname: Ogden
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Sullivan
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D002250:Carbon Radioisotopes / Q000378:metabolism; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D011110:Polymorphism, Genetic / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D055502:Secondary Prevention; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D002250:Carbon Radioisotopes; 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