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

Background Serotonin 5-HT2A receptors play an important role in the regulation of many functions that are disturbed in patients with major depressive disorder. Postmortem and positron emission tomography studies have reported both increased and decreased 5-HT2A receptor binding in different limbic and paralimbic regions. Methods We conducted a quantitative 5-HT2A receptor binding study using positron emission tomography and [18F]altanserin of four regions hypothesized to have altered levels of 5-HT2A receptors in major depressive disorder. Using a four-compartment model, the 5-HT2A receptor distribution was estimated by calculating the regional [18F]altanserin k3/k4 ratio in which k3 is the rate of binding to the receptor and k4 is the rate of dissociation from the receptor. Forty-six antidepressant-free patients with major depressive disorder and 29 healthy control subjects were enrolled. Results 5-HT2A receptor binding in the hippocampus was reduced by 29% in depressed subjects (p = .004). In other regions, 5-HT2A receptor binding was decreased (averaging 15%) but not significantly. Both groups had similar age-dependent decreases in 5-HT2A 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-HT2A receptor changes is still unclear.