Summary: A new study builds on previous findings that demonstrate EEG recordings of the rostral anterior cingulate cortex can predict eventual response to treatments for depression.
Source: McLean Hospital.
McLean Hospital and Harvard Medical School researchers believe they have uncovered a method that could be useful in predicting a depressed patient’s treatment prognosis, prior to starting treatment.
In the paper “Pretreatment Rostral Anterior Cingulate Cortex Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial,” currently available online and scheduled to appear in the June 2018 edition of JAMA Psychiatry, the investigative team details its work in identifying whether certain markers in the brain could allow clinicians to identify patients with a high or low likelihood of responding to certain treatments for depression.
The study was jointly first-authored by Diego A. Pizzagalli, PhD, and Christian A. Webb, PhD. “Our work shows that we could predict a patient’s response to an antidepressant by looking at the activation level of the rostral anterior cingulate cortex (ACC) region of the brain by using a non-invasive monitoring system to test brain activity called an electroencephalogram–also known as an EEG,” said Diego A. Pizzagalli, director of the McLean Imaging Center as well as the hospital’s Center For Depression, Anxiety and Stress Research and Laboratory for Translational and Affective Neuroscience. Webb, assistant professor at Harvard Medical School and director of the Treatment and Etiology of Depression in Youth Laboratory, noted that this is the first study to “demonstrate the ‘incremental predictive validity’ of this neural marker, that is, the fact that activity in this brain region predicts the likelihood of treatment response above and beyond the contribution of a range of low-cost and easily administered clinical and demographic characteristics previously shown to predict treatment outcome.”
For this study, the team built upon Pizzagalli’s previous work showing that EEG recordings of rostral ACC activity could predict the eventual response. “In that prior study, we saw that the higher the activity before the start of the treatment, the better the clinical response months later,” noted Pizzagalli, who is also a professor of psychiatry at Harvard Medical School.
For the new study, more than 300 patients were tested at four sites in the United States–using sertraline for the treatment group. “We showed that the rostral ACC marker predicted clinical response eight weeks later, even when statistically controlling for demographics and clinical variables previously linked to treatment response,” said Pizzagalli. “For those with the marker of good response, a clinician could tell patients that they have a high chance of benefitting from the intervention, and they should stay engaged in treatment,” he explained. Conversely, he said, for patients with the marker of low response, “clinicians could decide to start with more aggressive treatment at the outset, such as a combination of pharmacology and psychotherapy, and importantly, monitor these patients more closely.”
Soon, Webb, Pizzagalli, and their colleagues plan to deploy these approaches on patients at McLean Hospital to determine whether they can lead to treatment-specific predictions. “Our vision is to determine if an optimal combination of markers–including brain-based but also clinical and demographic characteristics–might allow us to predict response to drug A but not drug B or psychotherapy, for example,” Webb explained.
Also, if an ACC marker predicts better response, researchers might develop cognitive training that specifically targets this region, which could increase brain activation to accelerate or boost response to more traditional intervention. Pizzagalli and his team hope to engage in further research into this concept by testing patients with major depressive disorder.
Funding: The work was supported by the NIH/National Institute of Mental Health, National Coordinating Center at University of Texas Southwestern Medical Center and Data Center at Colunbia and Stony Brook Universities.
Source: Laura Neves – McLean Hospital
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial” by Diego A. Pizzagalli, PhD; Christian A. Webb, PhD; Daniel G. Dillon, PhD; Craig E. Tenke, PhD; Jürgen Kayser, PhD; Franziska Goer, MA; Maurizio Fava, MD; Patrick McGrath, MD; Myrna Weissman, PhD; Ramin Parsey, MD, PhD; Phil Adams, PhD; Joseph Trombello, PhD; Crystal Cooper, PhD; Patricia Deldin, PhD; Maria A. Oquendo, MD, PhD; Melvin G. McInnis, MD; Thomas Carmody, PhD; Gerard Bruder, PhD; and Madhukar H. Trivedi, MD in JAMA Psychiatry. Published April 11 2018,
Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial
Importance Major 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.
Objective To determine whether increased pretreatment rACC theta activity would predict symptom improvement regardless of randomization arm.
Design, Setting, and Participants A 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.
Interventions An 8-week course of sertraline or placebo.
Main Outcomes and Measures The 17-item Hamilton Rating Scale for Depression score (assessed at baseline and weeks 1, 2, 3, 4, 6, and 8).
Results The 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 Relevance Increased 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 Registration clinicaltrials.gov Identifier: NCT01407094