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 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 [(18)F]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 [(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 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.
Mintun
Mark A
MA
Department of Radiology, Mallinckrodt Institute of Radiology, Box 8225, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, MO 63110, USA.
Sheline
Yvette I
YI
Moerlein
Stephen M
SM
Vlassenko
Andrei G
AG
Huang
Yiyun
Y
Snyder
Abraham Z
AZ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods
D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin