title: Positron emission tomography quantification of serotonin transporter binding in medication-free bipolar disorder.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  5-HTT binding in six brain regions was compared between 17 depressed, unmedicated BD subjects and 31 HVs, using the outcome measure of VT/fP (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.
  
  
  RESULTS
  5-HTT binding (VT/fP ) did not differ between BD and HV groups considering six brain regions of interest simultaneously (P = 0.24). In contrast, alternative outcome measures (BPF*, BPP*, and BPND*) indicated lower binding in BD compared with HV across these six regions of interest (BPF*: P = 0.047; BPP*: P = 0.032; BPND*: 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, VT /fP . 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.
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.|Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Miller
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Everett
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.|Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.|Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: R Todd
authors.initials: RT
authors.lastname: Ogden
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, New York.|Department of Psychiatry, Columbia University, New York, New York.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.affiliation: Department of Psychiatry and Behavioral Science, Stony Brook University School of Medicine, Stony Brook, New York.
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
mesh_terms: D000328:Adult; D001596:Benzylamines; D001714:Bipolar Disorder / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013406:Suicide, Attempted; D055815:Young Adult
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTT; DASB; PET imaging; SERT; mood disorders