Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography.
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.
Cannon
Dara M
DM
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
Ichise
Masanori
M
Fromm
Stephen J
SJ
Nugent
Allison C
AC
Rollis
Denise
D
Gandhi
Shilpa K
SK
Klaver
Jacqueline M
JM
Charney
Dennis S
DS
Manji
Husseini K
HK
Drevets
Wayne C
WC
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
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides