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 | Jeffrey M Miller, Kathleen G Brennan, Todd R Ogden, Maria A Oquendo, Gregory M Sullivan, J John Mann, Ramin V Parsey |
Journal | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
(Neuropsychopharmacology)
Vol. 34
Issue 10
Pg. 2275-84
(Sep 2009)
ISSN: 1740-634X [Electronic] England |
PMID | 19458612
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antidepressive Agents
- Carbon Radioisotopes
- Piperazines
- Pyridines
- Serotonin Antagonists
- Receptor, Serotonin, 5-HT1A
- N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
|
Topics |
- Adult
- Antidepressive Agents
(therapeutic use)
- Carbon Radioisotopes
(metabolism)
- Cohort Studies
- Depressive Disorder, Major
(diagnostic imaging, drug therapy, metabolism)
- Female
- Gene Frequency
- Genotype
- Humans
- Male
- Middle Aged
- Piperazines
(metabolism, pharmacology)
- Polymorphism, Genetic
(genetics)
- Positron-Emission Tomography
(methods)
- Promoter Regions, Genetic
(genetics)
- Protein Binding
(drug effects)
- Pyridines
(metabolism, pharmacology)
- Receptor, Serotonin, 5-HT1A
(genetics, metabolism)
- Retrospective Studies
- Secondary Prevention
- Serotonin Antagonists
(metabolism, pharmacology)
- Young Adult
|