Positron emission tomography quantification of serotonin transporter binding in medication‐free bipolar disorder

Objectives : Bipolar disorder (BD) is associated with abnormalities in the serotonin transporter (5‐HTT), but specific in vivo findings have been discrepant. Using positron emission tomography (PET) and [ 11 C]DASB, we compared 5‐HTT binding between unmedicated depressed BD subjects and healthy volunteers (HVs). Experimental Design : 5‐HTT binding in six brain regions was compared between 17 depressed, unmedicated BD subjects and 31 HVs, using the outcome measure of V T / f P (proportional to the total number of available transporters). Alternative outcome measures were examined as well. 47% of BD were BP I; and 65% reported a prior suicide attempt. Principal Observations : 5‐HTT binding ( V T / f P ) did not differ between BD and HV groups considering six brain regions of interest simultaneously ( P  = 0.24). In contrast, alternative outcome measures (BP F *, BP P *, and BP ND *) indicated lower binding in BD compared with HV across these six regions of interest (BP F *: P  = 0.047; BP P *: P  = 0.032; BP ND *: P  = 0.031). 5‐HTT binding was unrelated to suicide attempt history, depression severity, bipolar subtype, or history of past substance use disorder. Conclusions : Choice of outcome measure strongly affects comparisons of serotonin transporter binding using PET with [ 11 C]DASB. We do not find evidence of abnormal 5‐HTT binding in bipolar depression using our primary outcome measure, V T / f P . However, we did observe lower 5‐HTT binding in BD with alternative outcome measures that are frequently used with [ 11 C]DASB. Relative merits and assumptions of different outcome measures are discussed. Evaluation in larger samples and during different mood states, including remission, is warranted. Synapse 70:24–32, 2016. . © 2015 Wiley Periodicals, Inc.