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Biol Psychiatry. 2009 Aug 1;66(3):223-30. doi: 10.1016/j.biopsych.2009.01.028. Epub 2009 Mar 17.

Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression.

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Department of Psychiatry, Columbia University College of Physicians & Surgeons, 1051 Riverside Drive, Unit #41, New York, NY 10032, USA.



Little is known about the serotonin-1A receptor (5-HT1A) in bipolar depression despite altered 5-HT1A binding in major depressive disorder. Utilizing positron emission tomography (PET) and the radioligand N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide ([Carbonyl-C-11]WAY-100635), 5-HT1A binding was compared between depressed bipolar disorder (BD) and controls.


Brain 5-HT1A binding potential (BP(F) = B(max)/K(D), where B(max) = total available receptors, and 1/K(D) = ligand affinity) was measured in 32 currently depressed, medication-free BD subjects and 47 controls. Participants were genotyped for the 5-HT1A promoter polymorphism C(-1019)G.


The bipolar depressed group demonstrated higher 5-HT1A BP(F) across all regions of interest (ROIs; p = .022). Post hoc analyses indicated that male BD patients had higher 5-HT1A BP(F) than male controls (p = .025), with higher 5-HT1A BP(F) found in every region (by 102% in raphe nuclei and 29% to 50% in the forebrain ROIs); whereas, female subgroups did not differ in 5-HT1A BP(F) (p = .32). Serotonin-1A BP(F) did not correlate with depression severity. The GG genotype was overrepresented at trend level in the BD group (p = .057). Number of G-allele copies was associated with higher 5-HT1A BP(F) in raphe (p = .0050), amygdala (p = .022), and hippocampus (p = .041).


Higher 5-HT1A BP(F) in bipolar depressed males suggests higher raphe autoreceptor binding, potentially causing less serotonin release and compensatory upregulation of forebrain postsynaptic 5-HT1A receptors. The raphe effect may be partly genetic. No difference in 5-HT1A BP(F) between BD and control females may reflect greater effect of prior antidepressant exposure in BD females.

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