Insular and hippocampal gray matter volume reductions in patients with major depressive disorder

Abstract

Background: Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder.

Methods: For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes.

Results: Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala.

Conclusions: The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.

Figure 1. Gray matter volume reductions in whole brain analysis.

Gray matter volume reductions in all MDD patients versus healthy controls (orange), and patients with recurrent depressive episodes versus healthy controls (red) (Table 3). (Whole brain analyses, p<0.001, k = 139; view: MNI: 36 23 -5).

Figure 2. Gray matter volume reductions in the region-of interest (ROI) parahippocampal gyrus+hippocampus bilaterally.

Gray matter volume reduction in ROI gyrus+hippocampus bilaterally in all MDD patients versus healthy controls (orange), patients with first depressive episode versus healthy controls (yellow) and patients with recurrent depressive episodes versus healthy controls (red) (Table 4). (Region-of-interest analyses, p<0.01, k = 109; view: MNI: −27 −29 −20).

Figure 3. Number of depressive episodes is negatively correlated with the right hippocampal gray matter volume.

A: Sagittal view (MNI x  = −6) depicting gray matter volumes correlating with number of depressive episodes. (Region-of-interest analyses, p<0.01, k = 109; Color bar represents negative correlation coefficient -r. (L: left; R: right)). B: Scatter plot depicting the negative correlation (r = −0.237; p = 0.006) of the right hippocampal cluster values (left panel) and the number of depressive episodes (SSPS Statistics 15.0 software package).