Decreased hippocampal 5-HT_2A 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 in patients 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 [¹⁸F]altanserin of four regions hypothesized to have altered levels of 5-HT_2A receptors in major depressive disorder. Using a four-compartment model, the 5-HT_2A receptor distribution was estimated by calculating the regional [¹⁸F]altanserin k ₃/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-HT_2A receptor binding in the hippocampus was reduced by 29% in depressed subjects (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-HT_2A 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.