Positron Emission Tomography Quantification of Serotonin-1A Receptor Binding in Medication-Free Bipolar Depression

• Published in: Biological psychiatry (1969) Vol. 66; no. 3; pp. 223 - 230
• Main Authors: Sullivan, Gregory M, Ogden, R. Todd, Oquendo, Maria A, Kumar, J.S. Dileep, Simpson, Norman, Huang, Yung-yu, Mann, J. John, Parsey, Ramin V
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2009; Elsevier
• Subjects: 5-HT1A receptor; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Bipolar; Bipolar Disorder - diagnostic imaging; Bipolar Disorder - genetics; Bipolar Disorder - pathology; Bipolar disorders; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Brain Mapping; Carbon Radioisotopes - metabolism; Depression; Female; Genotype; Humans; Magnetic Resonance Imaging - methods; Male; Medical sciences; Middle Aged; Mood disorders; Piperazines - metabolism; Polymorphism, Single Nucleotide - genetics; positron emission tomography (PET); Positron-Emission Tomography - methods; Protein Binding - physiology; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Pyridines - metabolism; Receptor, Serotonin, 5-HT1A - genetics; Receptor, Serotonin, 5-HT1A - metabolism; serotonin; Serotonin Antagonists - metabolism; Sex Factors; Young Adult; Bipolar; serotonin; depression; positron emission tomography (PET); 5-HT1A receptor; Radionuclide study; Mood disorder; Serotonin; Depression; Bipolar disorder; 5-HT1 Serotonine receptor; Serotonine receptor; Treatment; 5-HT1 A receptor; Neurotransmitter; Positron emission tomography; Emission tomography
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2009.01.028

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 ( BPF = Bmax / KD , where Bmax = total available receptors, and 1/ KD = 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 BPF across all regions of interest (ROIs; p = .022). Post hoc analyses indicated that male BD patients had higher 5-HT1A BPF than male controls ( p = .025), with higher 5-HT1A BPF 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 BPF ( p = .32). Serotonin-1A BPF 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 BPF in raphe ( p = .0050), amygdala ( p = .022), and hippocampus ( p = .041). Conclusions Higher 5-HT1A BPF 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 BPF between BD and control females may reflect greater effect of prior antidepressant exposure in BD females.