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 [¹¹C]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 [¹¹C]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 [¹¹C]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.