title: Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression.
abstract: BACKGROUND
  Vagus nerve stimulation (VNS) has antidepressant effects in treatment resistant major depression (TRMD); these effects are poorly understood. This trial examines associations of subacute (3 months) and chronic (12 months) VNS with cerebral metabolism in TRMD.
  
  
  OBJECTIVE
  (17)Fluorodeoxyglucose positron emission tomography was used to examine associations between 12-month antidepressant VNS response and cerebral metabolic rate for glucose (CMRGlu) changes at 3 and 12 months.
  
  
  METHODS
  Thirteen TRMD patients received 12 months of VNS. Depression assessments (Hamilton Depression Rating Scale [HDRS]) and PET scans were obtained at baseline (pre-VNS) and 3/12 months. CMRGlu was assessed in eight a priori selected brain regions (bilateral anterior insular [AIC], orbitofrontal [OFC], dorsolateral prefrontal [DLPFC], and anterior cingulate cortices [ACC]). Regional CMRGlu changes over time were studied in VNS responders (decreased 12 month HDRS by ≥50%) and nonresponders.
  
  
  RESULTS
  A significant trend (decreased 3 month CMRGlu) in the right DLPFC was observed over time in VNS responders (n = 9; P = 0.006). An exploratory whole brain analysis (P(uncorrected) = 0.005) demonstrated decreased 3 month right rostral cingulate and DLPFC CMRGlu, and increased 12 month left ventral tegmental CMRGlu in responders.
  
  
  CONCLUSIONS
  VNS response may involve gradual (months in duration) brain adaptations. Early on, this process may involve decreased right-sided DLPFC/cingulate cortical activity; longer term effects (12 months) may lead to brainstem dopaminergic activation. Study limitations included: a) a small VNS nonresponders sample (N = 4), which limited conclusions about nonresponder CMRGlu changes; b) no control group; and, c) patients maintained their psychotropic medications.
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA; Department of Neurology and Psychiatry, Saint Louis University, St. Louis, MO, USA. Electronic address: cconway@wustl.edu.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Conway
authors.forename: John T
authors.initials: JT
authors.lastname: Chibnall
authors.forename: Marie Anne
authors.initials: MA
authors.lastname: Gebara
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Price
authors.forename: Abraham Z
authors.initials: AZ
authors.lastname: Snyder
authors.forename: Mark A
authors.initials: MA
authors.lastname: Mintun
authors.forename: A D Bud
authors.initials: AD
authors.lastname: Craig
authors.forename: Martha E
authors.initials: ME
authors.lastname: Cornell
authors.forename: Dana C
authors.initials: DC
authors.lastname: Perantie
authors.forename: Luis A
authors.initials: LA
authors.lastname: Giuffra
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bucholz
authors.forename: Yvette I
authors.initials: YI
authors.lastname: Sheline
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D061218:Depressive Disorder, Treatment-Resistant / Q000000981:diagnostic imaging / Q000628:therapy*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013997:Time Factors; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*
keywords: Antidepressant; Depression; Positron emission tomography; Treatment resistant depression; Vagus nerve stimulation