Elevated Serotonin 1A Binding in Remitted Major Depressive Disorder: Evidence for a Trait Biological Abnormality

BACKGROUND: 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-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-HT(1A) 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. METHODS: 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 ≥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 BP(F). RESULTS: Remitted depressed subjects had higher 5-HT(1A) BP(F) than 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. CONCLUSIONS: Elevated 5-HT(1A) BP(F) 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-HT(1A) BP(F) and MDD, and 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.