title: Association between the serotonin transporter and cytokines: Implications for the pathophysiology of bipolar disorder.
abstract: BACKGROUND
  Reduced brain serotonin transporter (SERT) has been demonstrated in bipolar disorder (BD). The aim of this study was to explore the potential role of cytokines on reduced SERT in BD.
  
  
  METHODS
  Twenty-eight BD type I patients and 28 age- and gender-matched healthy controls (HCs) were recruited. Single photon emission computed tomography with the radiotracer 123I ADAM was used for SERT imaging. Regions of interest included the midbrain, thalamus, putamen and caudate. Seven cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1α (IL-1α), IL-1β, IL-4, IL-6 and IL-10, were measured using an enzyme linked immune-sorbent assay.
  
  
  RESULTS
  SERT availability in the midbrain and caudate was significantly lower in BD compared to HCs. IL-1β was significantly lower, whereas IL-10 was significantly higher in BD compared to HCs. Multiple linear regression analyses revealed that there were associations between cytokines, IL-1α, IL-1β, IL-6 and SERT availability in the midbrain but not in the thalamus, putamen and caudate. Furthermore, linear mixed effect analyses demonstrated that these associations were not different between HCs and BD.
  
  
  CONCLUSIONS
  While many cytokines have been proposed to be important in the pathophysiology of BD, our results demonstrated that significant associations between cytokines and SERT availability may explain the role of cytokines in mood regulation. However, these associations were not different between HCs and BD, which imply the role of these cytokines is not specific for BD.
authors.affiliation: Departments of Psychiatry Taipei Veterans General Hospital and National Yang Ming University, Taipei, Taiwan. Electronic address: c520608@ms64.hinet.net.
authors.forename: Yuan-Hwa
authors.initials: YH
authors.lastname: Chou
authors.affiliation: Departments of Psychiatry Taipei Veterans General Hospital and National Yang Ming University, Taipei, Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Hsieh
authors.affiliation: Departments of Psychiatry Taipei Veterans General Hospital and National Yang Ming University, Taipei, Taiwan.
authors.forename: Li-Chi
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Departments of Radiology Taipei Veterans General Hospital and National Yang Ming University, Taipei, Taiwan.
authors.forename: Jiing-Feng
authors.initials: JF
authors.lastname: Lirng
authors.affiliation: Departments of Nuclear Medicine, Taipei Veterans General Hospital and National Yang Ming University, Taipei, Taiwan.
authors.forename: Shyh-Jen
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism; D002928:Cinanserin / Q000031:analogs & derivatives / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult
chemical_list: C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; D016207:Cytokines; D050486:Serotonin Plasma Membrane Transport Proteins; D002928:Cinanserin
keywords: Bipolar disorder (BD); Cytokines; Serotonin transporter (SERT); Single photon emission computed tomography (SPECT)