Decreased interhemispheric coordination in treatment-resistant depression: a resting-state fMRI study

Abstract

Background: Previous studies have demonstrated that patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) differed at neural level. However, it remains unclear if these two subtypes of depression differ in the interhemispheric coordination. This study was undertaken for two purposes: (1) to explore the differences in interhemispheric coordination between these two subtypes by using the voxel-mirrored homotopic connectivity (VMHC) method; and (2) to determine if the difference of interhemispheric coordination can be used as a biomarker(s) to differentiate TRD from both TSD and healthy subjects (HS).

Methods: Twenty-three patients with TRD, 22 with TSD, and 19 HS participated in the study. Data of these participants were analyzed with the VMHC and seed-based functional connectivity (FC) approaches.

Results: Compared to the TSD group, the TRD group showed significantly lower VMHC values in the calcarine cortex, fusiform gyrus, hippocampus, superior temporal gyrus, middle cingulum, and precentral gyrus. Lower VMHC values were also observed in the TRD group in the calcarine cortex relative to the HS group. However, the TSD group had no significant change in VMHC value in any brain region compared to the HS group. Receiver operating characteristic curves (ROC) analysis revealed that the VMHC values in the calcarine cortex had discriminatory function distinguishing patients with TRD from patients with TSD as well as those participants in the HS group.

Conclusions: Lower VMHC values of patients with TRD relative to those with TSD and those in the HS group in the calcarine cortex appeared to be a unique feature for patients with TRD and it may be used as an imaging biomarker to separate patients with TRD from those with TSD or HS.

Figure 1. Statistical maps showing VMHC differences in different brain regions between studied groups.

Red denotes VMHC differences in the ANOVA analyses and the yellow/red color bar indicates the F value from the ANOVA analyses. Blue denotes lower VMHC and the green/blue color bars indicate the T value from post hoc analysis between compared groups. Of note, the two-sample t-test results within a mask showed significant group differences in the ANOVA analysis. VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.

Figure 2. Statistical maps showing seed-based FC differences between subject groups (seed: the left calcarine cortex).

Red denotes FC differences in the ANOVA analyses and the color bar indicate the F value from the ANOVA analyses. Blue denotes lower FC and the color bars indicate the T value from post hoc analysis between each pair of groups. Of note, the two-sample t-test results within a mask showed significant group differences in the ANOVA analysis. FC = functional connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.

Figure 3. Statistical maps showing seed-based FC differences between subject groups (seed: the right calcarine cortex).

Red denotes FC differences in the ANOVA analyses and the color bar indicate the F value from the ANOVA analyses. Red and blue denote higher and lower FC respectively and the color bars indicate the T value from post hoc analysis between each pair of groups. Of note, the two-sample t-test results within a mask showed significant group differences in the ANOVA analysis. FC = functional connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.

Figure 4. Bar plots representing the mean (and standard error) VMHC value of the calcarine cortex.

Significant differences found between the TRD group and the TSD group or the HS group (TRD vs TSD: p<0.001; TRD vs HS: p<0.01). VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.

Figure 5. Receiver operating characteristic (ROC) curves by using the mean VMHC value in the calcarine cortex.

A. Separating TRD from TSD; B. Separating TRD from HS; C. Separating TSD from HS. VMHC = voxel-mirrored homotopic connectivity, TRD = treatment-resistant depression, TSD = treatment-sensitive depression, HS = healthy subjects.