Elevated serotonin 1A binding in remitted major depressive disorder: evidence for a trait biological abnormality.

Abstract

BackgroundSeveral 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-naïve subjects with MDD within a major depressive episode (MDE) compared to healthy controls using positron emission tomography (PET). In the current study, we measured 5-HT1A receptor binding in unmedicated subjects with MDD during sustained remission, hypothesizing higher binding compared with healthy controls, and binding comparable to currently depressed antidepressant-naïve subjects, indicative of a biologic trait.MethodsWe compared 5-HT1A binding potential (BPF) assessed through PET scanning with [11C]WAY-100635 in 15 subjects with recurrent MDD in remission for ≥12 months and off antidepressant medication for ≥ six months, 51 healthy controls, and 13 antidepressant-naïve MDD subjects in a current MDE. Metabolite-corrected arterial input functions were acquired for estimation of BPF.ResultsRemitted depressed subjects had higher 5-HT1A BPF than 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.ConclusionsElevated 5-HT1A BPF among subjects with remitted MDD appears to be a trait abnormality in MDD, which may underlie recurrent major depressive episodes. Future studies should evaluate the role of genetic and environmental factors in producing elevated 5-HT1A BPF and MDD, and examine whether 5-HT1A BPF is a vulnerability factor to MDEs that could have a role in screening high-risk populations for MDD.