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Using positron emission tomography (PET) and [<jats:sup>11<\/jats:sup>C]DASB, we compared 5\u2010HTT binding between unmedicated depressed BD subjects and healthy volunteers (HVs). <jats:italic>Experimental Design<\/jats:italic>: 5\u2010HTT binding in six brain regions was compared between 17 depressed, unmedicated BD subjects and 31 HVs, using the outcome measure of <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>\/<jats:italic>f<\/jats:italic><jats:sub>P<\/jats:sub> (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. <jats:italic>Principal Observations<\/jats:italic>: 5\u2010HTT binding (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>\/<jats:italic>f<\/jats:italic><jats:sub>P<\/jats:sub>) did not differ between BD and HV groups considering six brain regions of interest simultaneously (<jats:italic>P<\/jats:italic>\u2009=\u20090.24). In contrast, alternative outcome measures (BP<jats:sub>F<\/jats:sub>*, BP<jats:sub>P<\/jats:sub>*, and BP<jats:sub>ND<\/jats:sub>*) indicated lower binding in BD compared with HV across these six regions of interest (BP<jats:sub>F<\/jats:sub>*: <jats:italic>P<\/jats:italic>\u2009=\u20090.047; BP<jats:sub>P<\/jats:sub>*: <jats:italic>P<\/jats:italic>\u2009=\u20090.032; BP<jats:sub>ND<\/jats:sub>*: <jats:italic>P<\/jats:italic>\u2009=\u20090.031). 5\u2010HTT binding was unrelated to suicide attempt history, depression severity, bipolar subtype, or history of past substance use disorder. <jats:italic>Conclusions<\/jats:italic>: Choice of outcome measure strongly affects comparisons of serotonin transporter binding using PET with [<jats:sup>11<\/jats:sup>C]DASB. We do not find evidence of abnormal 5\u2010HTT binding in bipolar depression using our primary outcome measure, <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>\/<jats:italic>f<\/jats:italic><jats:sub>P<\/jats:sub>. However, we did observe lower 5\u2010HTT binding in BD with alternative outcome measures that are frequently used with [<jats:sup>11<\/jats:sup>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. <jats:bold>Synapse 70:24\u201332, 2016.<\/jats:bold>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/syn.21868","type":"journal-article","created":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T23:42:52Z","timestamp":1443742972000},"page":"24-32","source":"Crossref","is-referenced-by-count":18,"title":["Positron emission tomography quantification of serotonin transporter binding in medication\u2010free bipolar disorder"],"prefix":"10.1002","volume":"70","author":[{"given":"Jeffrey M.","family":"Miller","sequence":"first","affiliation":[{"name":"Division of Molecular Imaging and Neuropathology New York State Psychiatric Institute New York New York"},{"name":"Department of Psychiatry Columbia University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin A.","family":"Everett","sequence":"additional","affiliation":[{"name":"Division of Molecular Imaging and Neuropathology New York State Psychiatric Institute New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria A.","family":"Oquendo","sequence":"additional","affiliation":[{"name":"Division of Molecular Imaging and Neuropathology New York State Psychiatric Institute New York New York"},{"name":"Department of Psychiatry Columbia University New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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