Prefrontal cortical response to emotional faces in individuals with major depressive disorder in remission

Abstract

Abnormalities in the response of the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to negative emotional stimuli have been reported in acutely depressed patients. However, there is a paucity of studies conducted in unmedicated individuals with major depressive disorder in remission (rMDD) to assess whether these are trait abnormalities. To address this issue, 19 medication-free rMDD individuals and 20 healthy comparison (HC) participants were scanned using functional magnetic resonance imaging while performing an implicit emotion processing task in which they labeled the gender of faces depicting negative (fearful), positive (happy) and neutral facial expressions. The rMDD and HC groups were compared using a region-of-interest approach for two contrasts: fear vs. neutral and happy vs. neutral. Relative to HC, rMDD showed reduced activation in left OFC and DLPFC to fearful (vs. neutral) faces. Right DLPFC activation to fearful (vs. neutral) faces in the rMDD group showed a significant positive correlation with duration of euthymia. The findings support deficits in left OFC and DLPFC responses to negative emotional stimuli during euthymic periods of MDD, which may reflect trait markers of the illness or a 'scar' due to previous depression. Recovery may also be associated with compensatory increases in right DLPFC functioning.

Figure 1. Left Orbitofrontal Cortex Decreases in rMDD individuals in the Fear vs. Neutral Condition

The 2mm axial-oblique slices display the region of orbitofrontal cortex (BA11) activation decreases in the fearful vs. neutral face condition in the remitted major depressive disorder (rMDD, n=19) group compared to the healthy comparison (HC, n=20) group, at P<0.005, uncorrected. The differences survived correction for multiple comparisons (P_FWE<0.05). Numbers to the left of the images are z-planes (Montreal Neurological Institute) in millimeters. The color bar shows the T values. The maxima was at coordinates x= −42mm, y= 22mm, z=−20mm; Ke= 866 voxels.

Figure 2. Left Dorsolateral Prefrontal Cortex Decreases in rMDD individuals in the Fear vs. Neutral Condition

The 2mm axial-oblique slices display the region of dorsolateral prefrontal cortex (BA9) activation decreases in the fearful vs. neutral face condition in the remitted major depressive disorder (rMDD, n=19) group compared to the healthy comparison (HC, n=20) group, at P<0.005, uncorrected. The differences survived correction for multiple comparisons (P_FWE<0.05). Numbers to the left of the images are z-planes (Montreal Neurological Institute) in millimeters. The color bar shows the T values. The maxima was at coordinates x= −50, y= 40, z= 20; Ke= 136 voxels.

Figure 3. Association between Dorsolateral Prefrontal Cortex Activation and Duration of Euthymia

Left: The sagittal image (Montreal Neurological Institute plane x= 12mm) displays the right dorsolateral prefrontal cortex region (BA9) in which response during the fearful vs. neutral face condition was significantly associated with duration of the current euthymic period in the participants with remitted major depressive disorder (n=19), at P<0.001. The color bar shows the T values. The maxima was at coordinates x=12, y= 46, z= 34; Ke= 75 voxels. Right: The graph demonstrates the positive correlation between the months of the current euthymic period in the participants with remitted major depressive disorder (n=19) and the percent of blood oxygen level dependent signal change extracted from the peak of the right dorsolateral prefrontal region shown in the image to the left, r= 0.69, r²= 0.47.