Objective biomarkers may have clinical utility in guiding personalized deep brain stimulation (DBS) of the subcallosal cingulate for the management of treatment-resistant depression, according to study findings published in the journal Nature.
The use of DBS of the subcallosal cingulate has been associated with long-term symptom relief among some patients with treatment-resistant depression, however, no useful strategies for stratifying patients likely and unlikely to achieve recovery from symptoms have been elucidated.
In this clinical trial, Deep Brain Stimulation for Treatment Resistant Depression With the Medtronic Activa PC+S (ClinicalTrials.gov Identifier: NCT01984710), patients (N=10; mean age, 49.4; 60% women) with treatment-resistant depression were recruited at Emory University. Participants underwent subcallosal cingulate DBS. Potential biomarkers for achieving clinical response and remission at 24 weeks were evaluated using an artificial intelligence approach. Response and remission were defined as a Hamilton Depression Rating Scale (HDRS-17) score reduction of 50% and a score of <8, respectively.
At baseline, the participants had an average HDRS-17 score of 22.3 (SD, 1.64). The mean score decreased to 7.3 (SD, 3.62) at week 24. These observed changes in scores indicated that 9 of the participants responded to treatment and 7 achieved remission.
[W]e derived the SDC as a common objective biomarker that accurately captured clinically defined ‘sick’ and ‘stable response’ states in all patients, as well as responding to changes in DBS stimulation.
Using the spectral features recorded during stimulation, a neural network classifier was able to differentiate between individuals who achieved a stable response from those who did not (area under the receiver operating characteristic curve [AUROC], 0.87).
The researchers observed that a positive slope in the spectral discriminative component (SDC) was a potential marker for the transition from “sick” to “stable response.” The largest changes in the SDC were in left alpha, left-low beta, left-high beta, right-high beta, and right-gamma band power. The SDC state was able to predict patient outcomes on a weekly basis (AUROC, 0.94).
All patients but 1 started DBS at the same frequency (3.5 V) and the dose was changed in 0.5-volt increments, as per psychiatrist discretion. The increase in stimulation voltage was found to decrease the SDC, corresponding with progress toward a “well” state (P =.039). However, the decrease in SDC did not correspond with significant improvements to HDRS-17 scores (P =.151).
Significant negative correlations between transition weeks to “stable response,” identified by SDC, and white matter integrity in the anterior hippocampus, insular, and dorsal anterior and posterior cingulate cortices were observed (all P <.05).
Using facial expressions of the patients extracted from videos of weekly clinical interviews, the changes in facial expressions were also related with SDC (F[1.00,51.74], 6.54; P =.01).
The major limitation of this study was the small sample size.
The researchers concluded, “In this study investigating long-term multimodal changes with SCC [subcallosal cingulate] DBS, we derived the SDC as a common objective biomarker that accurately captured clinically defined ‘sick’ and ‘stable response’ states in all patients, as well as responding to changes in DBS stimulation. In addition, the transition to reach the ‘stable response’ state identified from the SDC was correlated with structural and functional irregularities in the targeted white matter tracts and was further concordant with a data-driven analysis of complex facial expressions.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.