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Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression.

ABSTRACT: BACKGROUND:Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for medication-refractory major depression, yet the mechanisms of action for this intervention are poorly understood. Here we investigate cerebral cortex thickness as a possible biomarker of rTMS treatment response. METHODS:Longitudinal change in cortical thickness is evaluated relative to clinical outcomes across 48 participants in 2 cohorts undergoing left dorsolateral prefrontal cortex rTMS as a treatment for depression. RESULTS:Our results reveal changes in thickness in a region of the left rostral anterior cingulate cortex that correlate with clinical response, with this region becoming thicker in patients who respond favorably to rTMS and thinner in patients with a less favorable response. Moreover, the baseline cortical thickness in this region correlates with rTMS treatment response - those patients with thinner cortex before treatment tended to have the most clinical improvement. CONCLUSIONS:This study is the first analysis of longitudinal cortical thickness change with rTMS as a treatment for depression with similar results across two cohorts. These results support further investigation into the use of structural MRI as a possible biomarker of rTMS treatment response.

SUBMITTER: Boes AD

PROVIDER: S-EPMC6136654 | biostudies-literature | 2018 May - Jun

REPOSITORIES: biostudies-literature

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Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression.

Boes Aaron D AD Uitermarkt Brandt D BD Albazron Fatimah M FM Lan Martin J MJ Liston Conor C Pascual-Leone Alvaro A Dubin Marc J MJ Fox Michael D MD

Brain stimulation 20180131 3

<h4>Background</h4>Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for medication-refractory major depression, yet the mechanisms of action for this intervention are poorly understood. Here we investigate cerebral cortex thickness as a possible biomarker of rTMS treatment response.<h4>Methods</h4>Longitudinal change in cortical thickness is evaluated relative to clinical outcomes across 48 participants in 2 cohorts undergoing left dorsolateral prefrontal cortex rTMS ...[more]

PMID: 29454551

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Project description:ImportanceMajor depressive disorder (MDD) remains challenging to treat. Although several clinical and demographic variables have been found to predict poor antidepressant response, these markers have not been robustly replicated to warrant implementation in clinical care. Increased pretreatment rostral anterior cingulate cortex (rACC) theta activity has been linked to better antidepressant outcomes. However, no prior study has evaluated whether this marker has incremental predictive validity over clinical and demographic measures.ObjectiveTo determine whether increased pretreatment rACC theta activity would predict symptom improvement regardless of randomization arm.Design, setting, and participantsA multicenter randomized clinical trial enrolled outpatients without psychosis and with chronic or recurrent MDD between July 29, 2011, and December 15, 2015 (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care [EMBARC]). Patients were consecutively recruited from 4 university hospitals: 634 patients were screened, 296 were randomized to receive sertraline hydrochloride or placebo, 266 had electroencephalographic (EEG) recordings, and 248 had usable EEG data. Resting EEG data were recorded at baseline and 1 week after trial onset, and rACC theta activity was extracted using source localization. Intent-to-treat analysis was conducted. Data analysis was performed from October 7, 2016, to January 19, 2018.InterventionsAn 8-week course of sertraline or placebo.Main outcomes and measuresThe 17-item Hamilton Rating Scale for Depression score (assessed at baseline and weeks 1, 2, 3, 4, 6, and 8).ResultsThe 248 participants (160 [64.5%] women, 88 [35.5%] men) with usable EEG data had a mean (SD) age of 36.75 (13.15) years. Higher rACC theta activity at both baseline (b = -1.05; 95% CI, -1.77 to -0.34; P = .004) and week 1 (b = -0.83; 95% CI, -1.60 to -0.06; P < .04) predicted greater depressive symptom improvement, even when controlling for clinical and demographic variables previously linked with treatment outcome. These effects were not moderated by treatment arm. The rACC theta marker, in combination with clinical and demographic variables, accounted for an estimated 39.6% of the variance in symptom change (with 8.5% of the variance uniquely attributable to the rACC theta marker).Conclusions and relevanceIncreased pretreatment rACC theta activity represents a nonspecific prognostic marker of treatment outcome. This is the first study to date to demonstrate that rACC theta activity has incremental predictive validity.Trial registrationclinicaltrials.gov Identifier: NCT01407094.

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Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression.

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Rostral anterior cingulate cortex is a structural correlate of repetitive TMS treatment response in depression.

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