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

Dara M. Cannon, Masanori Ichise, Stephen J. Fromm, Allison C. Nugent, Denise Rollis, Shilpa K. Gandhi, Jacqueline M. Klaver, Dennis S. Charney, Husseini K. Manji, Wayne C. Drevets

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Background: 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. Methods: The 5-HTT binding-potential (BP) was assessed in 18 currently-depressed, unmedicated BD-subjects and 37 healthy controls using PET and [11C]DASB. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)207-217
Number of pages11
JournalBiological Psychiatry
Volume60
Issue number3
DOIs
StatePublished - 1 Aug 2006

Keywords

  • Bipolar disorder
  • [C-11]DASB
  • positron emission tomography
  • serotonin transporter

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