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Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder.

ABSTRACT: Existing neuroimaging studies of vagus nerve stimulation (VNS) in treatment resistant major depression (TRMD) suggest that many brain regions (eg, prefrontal cortex, thalamus, cingulate cortex, insular cortex) associated with mood disorders undergo alterations in blood flow/metabolism.Positron emission tomography (PET oxygen-15 labeled water or PET [(15)O] H(2)O) was used to identify changes in regional cerebral blood flow (rCBF) in response to immediate VNS in 13 subjects with TRMD. We hypothesized rCBF changes along the afferent pathway of the vagus and in regions associated with depression (eg, orbitofrontal cortex, amygdala, insular cortex).Six 90-second PET [(15)O] H(2)O scans were performed on 13 subjects in a VNS off-on sequence. After normalization for global uptake and realignment to standard atlas space, statistical t images (P < .005) were used to evaluate rCBF change.VNS induced significant rCBF decreases in the left and right lateral orbitofrontal cortex and left inferior temporal lobe. Significant increases were found in the right dorsal anterior cingulate, left posterior limb of the internal capsule/medial putamen, the right superior temporal gyrus, and the left cerebellar body. Post hoc analysis found small-to-moderate correlations between baseline acute change in rCBF and antidepressant response after 12 months of VNS.Regions undergoing rCBF change in response to acute VNS are consistent with the known afferent pathway of the vagus nerve and models of brain network in depression. Larger studies assessing the correlation between acute stimulation patterns and antidepressant outcomes with VNS are needed.

SUBMITTER: Conway CR

PROVIDER: S-EPMC3270206 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder.

Conway Charles R CR Sheline Yvette I YI Chibnall John T JT Bucholz Richard D RD Price Joseph L JL Gangwani Sunil S Mintun Mark A MA

Brain stimulation 20110403 2

<h4>Background</h4>Existing neuroimaging studies of vagus nerve stimulation (VNS) in treatment resistant major depression (TRMD) suggest that many brain regions (eg, prefrontal cortex, thalamus, cingulate cortex, insular cortex) associated with mood disorders undergo alterations in blood flow/metabolism.<h4>Objective/hypothesis</h4>Positron emission tomography (PET oxygen-15 labeled water or PET [(15)O] H(2)O) was used to identify changes in regional cerebral blood flow (rCBF) in response to imm ...[more]

PMID: 22037127

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Project description:BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS), as a noninvasive intervention, has beneficial effects on major depressive disorder based on clinical observations. However, the potential benefits and clinical role of taVNS in the treatment of major depressive disorder are still uncertain and have not been systematically evaluated. Therefore, we performed a systematic review and meta-analysis to evaluate the effectiveness and safety of taVNS in treating major depressive disorder.MethodsFour electronic databases, namely, Embase, MEDLINE, the Cochrane Library and PsycINFO, were searched for all related trials published through May 1, 2018. We extracted the basic information and data of the included studies and evaluated the methodological quality with the Cochrane risk of bias tool and the nonrandomized studies-of interventions (ROBINS-I) tool. A meta-analysis of the comparative effects was conducted using the Review Manager 5.3 software.ResultsA total of 423 citations from the databases were searched, and 4 studies with 222 individuals were included in the meta-analysis. The taVNS technique could decrease 24-item HAMD scores more than the sham intervention (MD: -4.23, 95% CI: -7.15, -1.31; P?=?.005) and was also more effective in decreasing Self-Rating Depression Scale scores ((MD: -10.34, 95% CI: -13.48, -7.20; P?<?.00001), Beck Depression Inventory scores (MD: -10.3, 95% CI: -18.1, -2.5; P?=?.01) and Self-Rating Anxiety Scale scores (MD: -6.57, 95% CI: -9.30, -3.84; P?<?.00001). However, there was no significant difference in the Hamilton Anxiety Rating Scale scores between the taVNS and sham taVNS groups (MD: -1.12, 95% CI: -2.56, 0.32; P?=?.13). No obvious adverse effects of taVNS treatment were reported in the included studies.ConclusionThe results of the analysis preliminarily demonstrated that taVNS therapy can effectively ameliorate the symptoms of major depressive disorder, providing an alternative technique for addressing depression. However, more well-designed RCTs with larger sample sizes and follow-ups are needed in future studies to confirm our findings.

Project description:BackgroundThe discovery of effective treatments for major depressive disorder (MDD) may help target different brain pathways. Invasive vagus nerve stimulation (VNS) is an effective neuromodulation technique for the treatment of MDD; however, the effectiveness of the noninvasive technique, transauricular VNS (taVNS), remains unknown. Moreover, a mechanistic understanding of the neural effects behind its biological and therapeutic effects is lacking. This review aimed to evaluate the clinical evidence and the neural and anti-inflammatory effects of taVNS in MDD.MethodsTwo searches were conducted using a systematic search strategy reviewed the clinical efficacy and neural connectivity of taVNS in MDD in humans and evaluated the changes in inflammatory markers after taVNS in humans or animal models of depression. A risk of bias assessment was performed in all human studies.ResultsOnly 5 studies evaluated the effects of taVNS in patients with depression. Although the studies demonstrated the efficacy of taVNS in treating depression, they used heterogeneous methodologies and limited data, thus preventing the conduct of pooled quantitative analyses. Pooled analysis could not be performed for studies that investigated the modulation of connectivity between brain areas; of the 6 publications, 5 were based on the same experiment. The animal studies that analyzed the presence of inflammatory markers showed a reduction in the level of pro-inflammatory cytokines or receptor expression.ConclusionsData on the clinical efficacy of taVNS in the treatment of MDD are limited. Although these studies showed positive results, no conclusions can be drawn regarding this topic considering the heterogeneity of these studies, as in the case of functional connectivity studies. Based on animal studies, the application of taVNS causes a decrease in the level of inflammatory factors in different parts of the brain, which also regulate the immune system. Therefore, further studies are needed to understand the effects of taVNS in patients with MDD.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder.

Publications

Brain blood-flow change with acute vagus nerve stimulation in treatment-refractory major depressive disorder.

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