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-HT1A) 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-HT1A 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-HT1A binding potential (BPF) assessed through PET scanning with [C-11] WAY-100635 in 15 subjects with recurrent MDD in remission for >= 12 months and off antidepressant medication for >= 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 BPF. Remitted depressed subjects had higher 5-HT1A BPF compared with healthy controls; this group difference did not vary significantly in magnitude across brain regions. 5-HT1A BPF was comparable in remitted and currently depressed subjects. Elevated 5-HT1A BPF 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-HT1A BPF and MDD, and should examine whether 5-HT1A BPF is a vulnerability factor to MDEs that could have a role in screening high-risk populations for MDD. Neuropsychopharmacology (2009) 34, 2275-2284; doi: 10.1038/npp.2009.54; published online 20 May 2009