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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Sullivan
Gregory M
GM
Department of Psychiatry, Columbia University College of Physicians & Surgeons, 1051 Riverside Drive, Unit #41, New York, NY 10032, USA. gms11@columbia.edu
Ogden
R Todd
RT
Oquendo
Maria A
MA
Kumar
J S Dileep
JS
Simpson
Norman
N
Huang
Yung-yu
YY
Mann
J John
JJ
Parsey
Ramin V
RV
D000328:Adult; D001714:Bipolar Disorder / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D012737:Sex Factors; D055815:Young Adult
D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide