Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression

Brain Stimul. 2013 Sep;6(5):788-97. doi: 10.1016/j.brs.2012.11.006. Epub 2013 Feb 13.

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/limitations: 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.

Keywords: Antidepressant; Depression; Positron emission tomography; Treatment resistant depression; Vagus nerve stimulation.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Depressive Disorder, Treatment-Resistant / diagnostic imaging
  • Depressive Disorder, Treatment-Resistant / therapy*
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Time Factors
  • Treatment Outcome
  • Vagus Nerve Stimulation / methods*