title: Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography.
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 [(11)C]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 [(11)C]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.
authors.affiliation: Mood and Anxiety Disorders Program, Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-2670, USA. daracannon@mail.nih.gov
authors.forename: Dara M
authors.initials: DM
authors.lastname: Cannon
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fromm
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.forename: Denise
authors.initials: D
authors.lastname: Rollis
authors.forename: Shilpa K
authors.initials: SK
authors.lastname: Gandhi
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Klaver
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Husseini K
authors.initials: HK
authors.lastname: Manji
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000814:Aniline Compounds; D001714:Bipolar Disorder / Q000175:diagnosis / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods / Q000706:statistics & numerical data*; D012016:Reference Values; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides