TY - JOUR
T1 - Pretreatment cerebral metabolic activity correlates with antidepressant efficacy of vagus nerve stimulation in treatment-resistant major depression
T2 - A potential marker for response?
AU - Conway, Charles R.
AU - Chibnall, John T.
AU - Gangwani, Sunil
AU - Mintun, Mark A.
AU - Price, Joseph L.
AU - Hershey, Tamara
AU - Giuffra, Luis A.
AU - Bucholz, Richard D.
AU - Christensen, Jon J.
AU - Sheline, Yvette I.
N1 - Funding Information:
This work was supported by funding from the National Institute of Mental Health CRC K08 award ( 1K08MH078156-01A1 ) and YIS K24 award ( 9K24MH07951006 ), the National Institute of Neurological Disorders and Stroke P30NS048056 , as well as funding from CRC's National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigators Award , and the Sidney R. Baer, Jr. Foundation . Cyberonics (Houston, TX) donated three cost-free devices to subjects in this trial.
Funding Information:
CRC has previously received grant funding for research from Cyberonics, the maker of the VNS device. He did not receive any funding from Cyberonics for this study. CRC is on the speaker's bureau for Merck and Bristol-Myers Squibb. CRC is receiving research grant funding from Bristol-Myers Squibb. MAM is an employee of Avid Radiopharmaceuticals. RDB receives royalty interest from Medtronics for licensing intellectual property in the manufacture of the StealthStation. YIS, JJC, JLP, JTC, LAG, SG, and TH have no financial relationships to disclose.
PY - 2012/8
Y1 - 2012/8
N2 - Background: Pretreatment brain activity in major depressive disorder correlates with response to antidepressant therapies, including pharmacotherapies and transcranial magnetic stimulation. The purpose of this trial was to examine whether pretreatment regional metabolic activity in selected regions of interest (ROIs) predicts antidepressant response following 12 months of vagus nerve stimulation (VNS) in 15 patients with treatment-resistant major depression (TRMD). Methods: Fluorodeoxyglucose positron emission tomography (FDG PET) was used to assess regional mean relative cerebral metabolic rate for glucose (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices) at baseline (prior to VNS activation). Depression severity was assessed at baseline and after 12 months of VNS using the Hamilton Depression Rating Scale (HDRS), with response defined as ≥ 50% reduction in HDRS from baseline. Results: Baseline CMRGlu in the anterior insular cortex differentiated VNS responders (n = 11) from nonresponders (n = 4) and correlated with HDRS change (r =.64, p =.01). In a regression analysis, lower anterior insular cortex CMRGlu (p =.004) and higher orbitofrontal cortex CMRGlu (p =.047) together predicted HDRS change (R2 =.58, p =.005). In a whole brain, voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex correlated with HDRS change (r =.78, p =.001). Limitations: Sample size was small, limiting statistical power; patients remained on their psychiatric medications; study was open-label and uncontrolled. Conclusions: This preliminary study suggests that pretreatment regional CMRGlu may be useful in predicting response to VNS in TRMD patients.
AB - Background: Pretreatment brain activity in major depressive disorder correlates with response to antidepressant therapies, including pharmacotherapies and transcranial magnetic stimulation. The purpose of this trial was to examine whether pretreatment regional metabolic activity in selected regions of interest (ROIs) predicts antidepressant response following 12 months of vagus nerve stimulation (VNS) in 15 patients with treatment-resistant major depression (TRMD). Methods: Fluorodeoxyglucose positron emission tomography (FDG PET) was used to assess regional mean relative cerebral metabolic rate for glucose (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices) at baseline (prior to VNS activation). Depression severity was assessed at baseline and after 12 months of VNS using the Hamilton Depression Rating Scale (HDRS), with response defined as ≥ 50% reduction in HDRS from baseline. Results: Baseline CMRGlu in the anterior insular cortex differentiated VNS responders (n = 11) from nonresponders (n = 4) and correlated with HDRS change (r =.64, p =.01). In a regression analysis, lower anterior insular cortex CMRGlu (p =.004) and higher orbitofrontal cortex CMRGlu (p =.047) together predicted HDRS change (R2 =.58, p =.005). In a whole brain, voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex correlated with HDRS change (r =.78, p =.001). Limitations: Sample size was small, limiting statistical power; patients remained on their psychiatric medications; study was open-label and uncontrolled. Conclusions: This preliminary study suggests that pretreatment regional CMRGlu may be useful in predicting response to VNS in TRMD patients.
KW - Depression
KW - Fluorodeoxyglucose PET
KW - Positron emission tomography
KW - Treatment response
KW - Treatment-resistant depression
KW - Vagus nerve stimulation
UR - http://www.scopus.com/inward/record.url?scp=84862119093&partnerID=8YFLogxK
U2 - 10.1016/j.jad.2012.02.007
DO - 10.1016/j.jad.2012.02.007
M3 - Article
C2 - 22397889
AN - SCOPUS:84862119093
VL - 139
SP - 283
EP - 290
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
IS - 3
ER -