Altered Connectivity of the Anterior Cingulate and the Posterior Superior Temporal Gyrus in a Longitudinal Study of Later-life Depression

Abstract

Patients with later-life depression (LLD) show abnormal gray matter (GM) volume, white matter (WM) integrity and functional connectivity in the anterior cingulate cortex (ACC) and posterior superior temporal gyrus (pSTG), but it remains unclear whether these abnormalities persist over time. We examined whether structural and functional abnormalities in these two regions are present within the same subjects during depressed vs. remitted phases. Sixteen patients with LLD and 30 healthy subjects were studied over a period of 1.5 years. Brain images obtained with a 3-Tesla magnetic resonance imaging (MRI) system were analyzed by voxel-based morphometry of the GM volume, and diffusion tensor imaging (DTI) and resting-state functional MRI were used to assess ACC-pSTG connectivity. Patients with LLD in the depressed and remitted phases showed significantly smaller GM volume in the left ACC and left pSTG than healthy subjects. Both patients with LLD in the depressed and remitted phases had significantly higher diffusivities in the WM tract of the left ACC-pSTG than healthy subjects. Remitted patients with LLD showed lower functional ACC-pSTG connectivity compared to healthy subjects. No difference was found in the two regions between depressed and remitted patients in GM volume, structural or functional connectivity. Functional ACC-pSTG connectivity was positively correlated with lower global function during remission. Our preliminary data show that structural and functional abnormalities of the ACC and pSTG occur during LLD remission. Our findings tentatively reveal the brain pathophysiology involved in LLD and may aid in developing neuroanatomical biomarkers for this condition.

Keywords: cingulate cortex; connectivity; gray matter volume; late-life depression; magnetic resonance imaging; resting state functional magnetic resonance imaging; superior temporal gyrus; white matter integrity.

Figure 1

Reduced gray matter (GM) volume in patients with later-life depression (LLD). Patients with acute LLD showed significantly smaller GM volumes in the left anterior cingulate cortex (ACC) and posterior superior temporal gyrus (pSTG) than did healthy subjects. Patients with LLD in remission showed significantly smaller GM volumes in the left ACC and pSTG than healthy participants. The cross-hairs mark the coordinates of the voxel of maximal statistical significance.

Figure 2

Structural white matter (WM) connectivity between the left anterior cingulate and posterior superior temporal gyrus (ACC–pSTG). Patients with LLD (n = 13) in the depressed and remitted phases demonstrated significantly higher WM connectivity in the ACC–pSTG region than did healthy subjects (n = 21), in terms of mean, radial and axial diffusivity, but not in fractional anisotropy. Tangerine bars represent the median value of Z-score for each diffusivity. Y-axis represents z-score. *p < 0.05 by Mann-Whitney U test or Wilcoxon signed ranks test.

Figure 3

Functional connectivity of the left anterior cingulate and posterior superior temporal gyrus (ACC–pSTG). Patients with remitted LLD (n = 16) showed lower functional connectivity in the left ACC–pSTG than healthy subjects (n = 30). Tangerine bars represent the median value of Z-score for each group. *p < 0.05 by Mann-Whitney U test.

Figure 4

The scatter plots of between functional and structural connectivity and the global functioning. Functional connectivity of anterior cingulate and posterior superior temporal gyrus pSTG (ACC–pSTG) showed a significantly inverse correlation in the score of global assessment of functioning (A) and structural ACC–pSTG connectivity (B) in patients with LLD in the remitted phase (red circle), but not in patients with LLD in the depresses phase (blue triangle) or healthy participants (gray diamond).