title: [11C]Mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging.
abstract: BACKGROUND
  Lack of benefit from antidepressant drug therapy is a major source of human suffering, affecting at least 25% of people with major depressive disorder. We want to know whether nonresponse to antidepressants can be linked to aberrant neuroreceptor binding.
  
  
  OBJECTIVE
  This study aims to assess the antidepressant binding in brain regions of depressed nonresponders compared with healthy controls.
  
  
  METHODS
  Healthy volunteers and depressed subjects who had failed to benefit from at least 2 antidepressant treatments were recruited by newspaper advertisements. All subjects had received no antidepressant medication for at least 2 months before positron emission tomography (PET) that was carried out with [11C]mirtazapine. Kinetic parameters of [11C]mirtazapine were determined from PET data in selected brain regions by the simplified reference tissue model.
  
  
  RESULTS
  Binding potentials of [11C]mirtazapine in cerebral cortical regions were lower in depressed nonresponders than in healthy controls. Removal rates of [11C]mirtazapine were higher in diencephalic regions of depressed nonresponders than in healthy controls.
  
  
  CONCLUSIONS
  PET neuroimaging with [11C]mirtazapine showed aberrant neuroreceptor binding in brain regions of depressed subjects who had failed to benefit from treatment with antidepressant drugs.
authors.affiliation: Center for Psychiatric Research, Psychiatric Hospital of Aarhus University, Risskov, 8240, Denmark. dfsmithdfsmith@gmail.com
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smith
authors.forename: Bo S
authors.initials: BS
authors.lastname: Stork
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ashkanian
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.forename: Dirk
authors.initials: D
authors.lastname: Bender
authors.forename: Hélène
authors.initials: H
authors.lastname: Audrain
authors.forename: Karina H
authors.initials: KH
authors.lastname: Vase
authors.forename: Søren B
authors.initials: SB
authors.lastname: Hansen
authors.forename: Poul
authors.initials: P
authors.lastname: Videbech
authors.forename: Raben
authors.initials: R
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D049268:Positron-Emission Tomography; D011485:Protein Binding
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002250:Carbon Radioisotopes; D008803:Mianserin; D000078785:Mirtazapine