Decreased hippocampal 5-HT2A receptor binding in major depressive disorder:: In vivo measurement with [18F]Altanserin positron emission tomography

Background: Serotonin 5-HT(2A) receptors play an important role in the regulation of many functions that are disturbed inpatients with major depressive disorder. Postmortem and positron emission tomography studies have reported both increased and decreased 5-HT(2A) receptor binding in different limbic and paralimbic regions. Methods: We conducted a quantitative 5-HT(2A) receptor binding study using positron emission tomography and [(18)F]altanserin of four regions hypothesized to have altered levels of 5-HT2, receptors in major depressive disorder. Using a four-compartment model, the 5-HT(2A) receptor distribution was estimated by calculating the regional [(18)F]altanserin k(3)/k(4) ratio in which k(3) is the rate of binding to the receptor and k(4) is the rate of dissociation from the receptor. Forty-six antidepressant-free patient, with major depressive disorder and 29 healthy control subjects were enrolled. Results: 5-HT(2A) receptor binding in the hippocampus was reduced by 29% in depressed sublects (p = .004). In other regions, 5-HT(2A) receptor binding was decreased (averaging 15%) but not significantly. Both groups had similar age-dependent decreases in 5-HT2, receptors throughout all brain regions. Conclusions: Altered serotoninergic function in the hippocampus is likely involved in the disturbances of mood regulation in major depressive disorder, although the specific role of the 5-HT(2A) receptor changes is still unclear.