Elevated serotonin 1A binding in remitted major depressive disorder: evidence for a trait biological abnormality.
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.
Miller
Jeffrey M
JM
Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University, New York, NY 10033, USA. jm2233@columbia.edu
Brennan
Kathleen G
KG
Ogden
Todd R
TR
Oquendo
Maria A
MA
Sullivan
Gregory M
GM
Mann
J John
JJ
Parsey
Ramin V
RV
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
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