title: Platelet serotonin transporter function predicts default-mode network activity.
abstract: BACKGROUND
  The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.
  
  
  METHODS
  A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax.
  
  
  RESULTS
  The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity.
  
  
  CONCLUSIONS
  This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Scharinger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rabl
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian H
authors.initials: CH
authors.lastname: Kasess
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Bernhard M
authors.initials: BM
authors.lastname: Meyer
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria; Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Tina
authors.initials: T
authors.lastname: Hofmaier
authors.affiliation: Department of Psychology, Dresden University of Technology, Dresden, Germany.
authors.forename: Kersten
authors.initials: K
authors.lastname: Diers
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Lucie
authors.initials: L
authors.lastname: Bartova
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Pail
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria; Department of Statistics and Probability Theory, Vienna University of Technology, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huf
authors.affiliation: Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Uzelac
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Beate
authors.initials: B
authors.lastname: Hartinger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria; Department of Statistics and Probability Theory, Vienna University of Technology, Vienna, Austria.
authors.forename: Klaudius
authors.initials: K
authors.lastname: Kalcher
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Helmuth
authors.initials: H
authors.lastname: Haslacher
authors.affiliation: Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyer-Lindenberg
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Freissmuth
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Windischberger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Matthäus
authors.initials: M
authors.lastname: Willeit
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Rupert
authors.initials: R
authors.lastname: Lanzenberger
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.affiliation: Department of Psychology, Dresden University of Technology, Dresden, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Brocke
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
authors.forename: Ewald
authors.initials: E
authors.lastname: Moser
authors.affiliation: Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Sitte
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Pezawas
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D063132:Connectome; D005260:Female; D059907:Functional Neuroimaging; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin