Midline and right frontal brain function as a physiologic biomarker of remission in major depression

Abstract

Prior investigations have reported that changes in the prefrontal electroencephalogram (EEG) precede symptom improvement from antidepressant medications, and could serve as a biomarker of treatment outcome in major depressive disorder (MDD). A new physiologically defined region of interest (ROI), overlying the midline and right frontal (MRF) cortical area, was examined here for a relationship between early decreases in theta-band cordance and remission. Subjects were 72 adults with unipolar MDD who had completed placebo-controlled antidepressant treatment trials, with 37 randomized to medication and 35 to placebo. We assessed changes in cordance and absolute and relative power in the MRF region at 48 h, 1 week, and 2 weeks after start of drug, as potential predictors of remission (final score on the 17-item Hamilton Depression Rating Scale of 5 or below. Out of 37 medication-treated subjects, 11 (30%) remitted versus 6 of 35 placebo subjects (17%). Change in MRF cordance 1 and 2 weeks after the beginning of treatment was significantly associated with remission in medication-treated subjects at 1 week, with receiver operating characteristic (ROC) analysis yielding 0.76 area under the curve. Decreases in MRF cordance at 1 week predicted remission with medication with 69% overall accuracy (90% sensitivity; 60% specificity). MRF cordance changes were not associated with remission with placebo. Absolute and relative power did not differentiate groups. These results suggest that remission may be predictable from physiologic measurements after 1 week of treatment, and that this region merits further investigation in the neurobiology of treatment response.

Figure 1. Electrode Placements and Regions of Interest

Panel (a) shows the placement of 35 electrodes in accordance with the International 10–20 system; previously examined Region of Interest (ROI) included FP1, FPz, and FP2 electrodes (marked with asterisks). In Panel (b), the Midline and Right Frontal Cortical (MRFC) ROI includes Fpz, Fz, Fp2, AF2, F4, and F8 electrodes, outlined with black lines. Images depict the head from above.

Figure 2. Clinical Symptoms Over Time

Changes in Ham-D17 are plotted for the four groups (remitters and non-remitters on medication or placebo).

Figure 3. Time Course of MRFC Change

Changes in MRFC at 48 hrs and 1 and 2 weeks of treatment, in subjects in remission (solid line with circles) and non-remission subjects (dashed line with squares) subjects. Groups show statistical separation at one and two weeks of exposure to medication. * p < 0.05