Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: A voxel-based morphometry study
Introduction
Major depressive disorder (MDD) is ranked by the World Health Organization as the first leading cause of years lived with disability [1]. MDD is characterized by the presence of both affective (e.g., anhedonia, anergy, self-loathing and guilt) and cognitive (e.g., deficient working memory, impaired executive function) symptoms [2], [3]. The etiology and pathophysiology of MDD remains unknown.
Current models of MDD regard functional deficits in limbic-cortical circuitry, including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), insula and temporal pole (TP), in MDD [4], [5]. Structural gray matter abnormalities may contribute to the functional abnormalities observed in MDD. Indeed, volumetric reductions of OFC and DLPFC are well known, established by numerous volumetric magnetic resonance imaging (MRI) studies [3], [6], [7], [8]. The insula and the temporal pole connected with OFC and both play a central role in emotional processing [1], [9]. However, few morphometric MRI studies have assessed these regions in MDD, and preliminary results either await replication or are in disagreement.
In contrast to the large number of imaging studies exploring cerebral cortex in MDD, less attention has been paid to possible abnormalities in cerebellum. Traditionally, the emphasis of studies on cerebellar function has been on the coordination of somatic motor function, control of muscle tone and equilibrium [10]. There is increasing recognition that the cerebellum contributes to cognitive processing and emotional control in addition to its role in motor coordination [11]. A recent meta-analytic study in MDD noted that the cerebellum was one of the most consistently identified regions involved in the pathophysiology of the illness [4]. To our knowledge, only two studies have examined cerebellar gray matter in MDD patients and the results have been inconsistent. Frodl et al. found gray matter reduction in the cerebellum of patients with MDD [8], while Pillay et al. failed to find such evidence [12].
Voxel-based morphometry (VBM) has become an established research method in recent years. It is a user-independent, fully automated method of analysis which allows for unbiased exploration of gray matter density (GMD) changes across the whole brain without a priori specification of region of interest [13]. In this study, we used optimized VBM to examine the extent to which gray matter abnormalities were present in first-episode MDD patients compared to healthy controls. Based on prior work, we hypothesized that patients with depression would show smaller gray matter in regions comprising limbic-cortical circuits such as OFC, DLPFC, insula and TP. We further predicted that gray matter reduction in cerebellum would be observed. In addition, we hypothesized that severity of depression would correlate negatively with GMD values.
Section snippets
Subjects
Twenty-two patients with MDD were recruited from an outpatient clinic located at the Department of Psychiatry in Anding Hospital, Capital Medical University, China. 30 healthy controls were recruited by advertisements from the local community. The two groups were matched by age, gender and education. All participants were right-handed. The relevant Human Research Ethics Review Committees approved the study protocol, and the participants gave written informed consent after a complete description
Results
As shown in Table 1, no significant differences in age, gender distribution and years of education were observed between MDD patients and healthy controls.
Compared to healthy controls, the patients with MDD showed reduced GMD in the left inferior/middle frontal gyrus (Brodmann Area [BA] 47), the right middle/inferior frontal gyrus (BA 9/10/45/46), the right orbitofrontal gyrus (BA 11), the bilateral temporal poles (BA 38), the right superior temporal gyrus (BA 22), the bilateral middle temporal
Discussion
To our knowledge, this is the first VBM study that reports significant GMD reductions of bilateral anterior insular cortex in first-episode MDD patients. We also found decreased GMD in the regions of the right medial and left lateral OFC, the right DLPFC, bilateral TP and right STG, the left parahippocampal gyrus and the left cerebellum in MDD patients compared to healthy controls. Moreover, GMD values of the right DLPFC were negatively correlated with score of the depression rating scale.
Conclusion
In conclusion, our findings provided additional evidence for gray matter structural abnormalities in brain regions comprising limbic-cortical circuits, including the OFC, DLPFC, anterior insula cortex and TP, in the pathophysiology of MDD. Our data also suggested that the cerebellum should be integrated in models of the pathophysiology of MDD and need further exploration.
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