Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients.
BACKGROUND
Vagus nerve stimulation (VNS) has shown promising antidepressant effects in treatment-resistant depression, but the mechanisms of action are not known. Cerebrospinal fluid (CSF) studies in epilepsy patients show that VNS alters concentrations of monamines and gamma-aminobutyric acid (GABA), neurotransmitter systems possibly involved in the pathogenesis of depression.


METHODS
Twenty-one adults with treatment-resistant, recurrent, or chronic major depression underwent standardized lumbar puncture for collection of 12 mL CSF on three separate but identical procedure days during participation in the VNS D-02 clinical trial. All subjects remained on stable regimens of mood medications. Collections were made at baseline (2 weeks after surgical implantation but before device activation), week 12 (end of the acute-phase study), and week 24. Cerebrospinal fluid concentrations of norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined with high-performance liquid chromatography. Concentrations of GABA were assayed with mass spectrometry.


RESULTS
Comparison of sham versus active VNS revealed a significant (mean 21%) VNS-associated increase in CSF HVA. Mean CSF concentrations of NE, 5-HIAA, MHPG, and GABA did not change significantly. Higher baseline HVA/5-HIAA ratio predicted worse clinical outcome.


CONCLUSIONS
Although several of the CSF neurochemical effects we observed in this VNS study were similar to those described in the literature for antidepressants and electroconvulsive therapy, the results do not suggest a putative antidepressant mechanism of action for VNS.
Carpenter
Linda L
LL
Laboratory for Clinical Neuroscience, Butler Hospital, Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, Rhode Island 02906, USA. Linda_Carpenter_MD@Brown .edu
Moreno
Francisco A
FA
Kling
Mitchel A
MA
Anderson
George M
GM
Regenold
William T
WT
Labiner
David M
DM
Price
Lawrence H
LH
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003863:Depression / Q000134:cerebrospinal fluid* / Q000628:therapy; D004599:Electric Stimulation Therapy; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009638:Norepinephrine / Q000134:cerebrospinal fluid*; D013129:Spinal Puncture / Q000379:methods; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology / Q000528:radiation effects*; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid*
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine; D006719:Homovanillic Acid