Serotonin Transporter Binding in Bipolar Disorder Assessed using [ 11C]DASB and Positron Emission Tomography

• Published in: Biological psychiatry (1969) Vol. 60; no. 3; pp. 207 - 217
• Main Authors: Cannon, Dara M., Ichise, Masanori, Fromm, Stephen J., Nugent, Allison C., Rollis, Denise, Gandhi, Shilpa K., Klaver, Jacqueline M., Charney, Dennis S., Manji, Husseini K., Drevets, Wayne C.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2006; Elsevier Science
• Subjects: [C-11]DASB; Adolescent; Adult; Adult and adolescent clinical studies; Analysis of Variance; Aniline Compounds; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - diagnosis; Bipolar Disorder - metabolism; Bipolar disorders; Brain - diagnostic imaging; Brain - metabolism; Brain Mapping - methods; Carbon Radioisotopes; Female; Humans; Male; Medical sciences; Middle Aged; Mood disorders; positron emission tomography; Positron-Emission Tomography - methods; Positron-Emission Tomography - statistics & numerical data; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Reference Values; Sensitivity and Specificity; Serotonin Plasma Membrane Transport Proteins - metabolism; serotonin transporter; Sulfides; Bipolar disorder; [C-11]DASB; positron emission tomography; serotonin transporter; Radionuclide study; Mood disorder; Serotonin transporter; Emission tomography
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.05.005

Evidence from neuroimaging post-mortem, and genetic studies suggests that bipolar disorder (BD) is associated with abnormalities of the serotonin-transporter (5-HTT) system. Because of various limitations of these studies, however, it has remained unclear whether 5-HTT binding is abnormal in unmedicated BD-subjects. This study used PET and [ 11C]DASB, a radioligand that afforded higher sensitivity and specificity for the 5-HTT than previously available radioligands, to compare 5-HTT binding between BD and control subjects. The 5-HTT binding-potential (BP) was assessed in 18 currently-depressed, unmedicated BD-subjects and 37 healthy controls using PET and [ 11C]DASB. In BD, the mean 5-HTT BP was increased in thalamus, dorsal cingulate cortex (DCC), medial prefrontal cortex and insula and decreased in the brainstem at the level of the pontine raphe-nuclei. Anxiety ratings correlated positively with 5-HTT BP in insula and DCC, and BP in these regions was higher in subjects manifesting pathological obsessions and compulsions relative to BD-subjects lacking such symptoms. Subjects with a history of suicide attempts showed reduced 5-HTT binding in the midbrain and increased binding in anterior cingulate cortex versus controls and to BD-subjects without attempts. This is the first study to report abnormalities in 5-HTT binding in unmedicated BD-subjects. The direction of abnormality in the brainstem was opposite to that found in the cortex, thalamus, and striatum. Elevated 5-HTT binding in the cortex may be related to anxiety symptoms and syndromes associated with BD.