title: The effects of low-dose ketamine on the prefrontal cortex and amygdala in treatment-resistant depression: A randomized controlled study.
abstract: BACKGROUND
  Low-dose ketamine has been found to have robust and rapid antidepressant effects. A hypoactive prefrontal cortex (PFC) and a hyperactive amygdala have been suggested to be associated with treatment-resistant depression (TRD). However, it is unclear whether the rapid antidepressant mechanisms of ketamine on TRD involve changes in glutamatergic neurotransmission in the PFC and the amygdala.
  
  
  METHODS
  A group of 48 TRD patients were recruited and equally randomized into three groups (A: 0.5 kg/mg-ketamine; B: 0.2 kg/mg-ketamine; and C: normal saline [NS]). Standardized uptake values (SUV) of glucose metabolism measured by (18) F-FDG positron-emission-tomography before and immediately after a 40-min ketamine or NS infusion were used for subsequent region-of-interest (ROI) analyses (a priori regions: PFC and amygdala) and whole-brain voxel-wise analyses and were correlated with antidepressant responses, as defined by the Hamilton depression rating scale score. The (18) F-FDG signals were used as a proxy measure of glutamate neurotransmission.
  
  
  RESULTS
  The ROI analysis indicated that Group A and Group B, but not Group C, had increases in the SUV of the PFC (group-by-time interaction: F = 7.373, P = 0.002), whereas decreases in the SUV of the amygdala were observed in all three groups (main effect of time, P < 0.001). The voxel-wise analysis further confirmed a significant group effect on the PFC (corrected for family-wise errors, P < 0.05; post hoc analysis: Group A<Group C, Group B<Group C). The SUV differences in the PFC predicted the antidepressant responses at 40 and 240 min post-treatment. The PFC changes did not differ between those with and without side effects.
  
  
  CONCLUSIONS
  Ketamine's rapid antidepressant effects involved the facilitation of glutamatergic neurotransmission in the PFC.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Mu-Hong
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.affiliation: Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Bang-Hung
authors.initials: BH
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Pei-Chi
authors.initials: PC
authors.lastname: Tu
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 112, Taiwan.|Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, 112, Taiwan.|Institute of Brain Science, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Tung-Ping
authors.initials: TP
authors.lastname: Su
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects*; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy; D061218:Depressive Disorder, Treatment-Resistant / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019788:Fluorodeoxyglucose F18; D018698:Glutamic Acid; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D019275:Radiopharmaceuticals
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D018698:Glutamic Acid; D007649:Ketamine
keywords: glucose; ketamine; prefrontal cortex; treatment-resistant depression
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