Bora E, Fornito A, Pantelis C, Yucel M. Gray matter abnormalities in Major Depressive Disorder: a meta-analysis of voxel based morphometry studies. J Affect Disord 138: 9-18

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Victoria, Australia.
Journal of Affective Disorders (Impact Factor: 3.38). 04/2011; 138(1-2):9-18. DOI: 10.1016/j.jad.2011.03.049
Source: PubMed


Voxel-based morphometry (VBM) has been widely used to quantify structural brain changes associated with Major Depressive Disorder (MDD). While some consistent findings have been reported, individual studies have also varied with respect to the key brain regions affected by the illness, and how these abnormalities are related to patients' clinical characteristics. Here, we aimed to identify those brain regions that most consistently showed gray matter anomalies in MDD, and their clinical correlates, using meta-analytic techniques.
A systematic search of VBM studies was applied in MDD. Signed differential mapping, a new coordinate based neuroimaging meta-analysis technique, was applied to data collated from a total of 23 studies comparing regional gray matter volumes of 986 MDD patients and 937 healthy controls.
Gray matter was significantly reduced in a confined cluster located in the rostral anterior cingulate cortex (ACC). There were also gray matter reductions in dorsolateral and dorsomedial prefrontal cortex and decrease in the latter region was evident in patients with multiple-episodes. Amygdala and parahippocampal gray matter volumes were significantly reduced in studies including patients with comorbid anxiety disorders, as well as in first-episode/drug free samples.
Gray matter reduction in rostral ACC was the most consistent finding in VBM studies of MDD. The evidence for reductions in other regions within fronto-subcortical and limbic regions was less consistent. The associations between these gray matter anomalies and clinical characteristics, particularly measures relating to illness duration, suggest that chronic MDD has a robust and deleterious, albeit spatially focal, effect on brain structure.

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    • "Thus, it should not be surprising that the insular cortex is implicated in the pathophysiology of depression and may be dysfunctional in individuals with affective disorders. For example, structural differences of the anterior insular cortex have been shown in adult MDD compared to healthy controls (Bora et al., 2012; Peng et al., 2011; Soriano-Mas et al., 2011; Sprengelmeyer et al., 2011; Stratmann et al., 2014; Takahashi et al., 2010) and task-based fMRI studies have shown both increased (Hamilton et al., 2012; Sliz and Hayley, 2012) and decreased activation (Townsend et al., 2010) of the anterior insular cortex in adults with MDD compared to healthy controls. While neuroimaging in adult depression suggests a road map to understanding depressive symptoms in the developing brain, direct translation of the adult findings of differences in insular cortex activation as characteristics of adolescent depressive symptoms may be obscured by the major re-organization of the brain occurring from puberty to early adulthood (Gogtay et al., 2004). "
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    ABSTRACT: Background: Major depressive disorder (MDD) is a leading cause of disability worldwide and occurs commonly first during adolescence. The insular cortex (IC) plays an important role in integrating emotion processing with interoception and has been implicated recently in the pathophysiology of adult and adolescent MDD. However, no studies have yet specifically examined the IC in adolescent MDD during processing of faces in the sad- happy continuum. Thus, the aim of the present study is to investigate the IC during sad and happy face processing in adolescents with MDD compared to healthy controls (HCL). Methods: Thirty-one adolescents (22 female) with MDD and 36 (23 female) HCL underwent a well- validated emotional processing fMRI paradigm that included sad and happy face stimuli. Results: The MDD group showed significantly less differential activation of the anterior/middle insular cortex (AMIC) in response to sad versus happy faces compared to the HCL group. AMIC also showed greater functional connectivity with right fusiform gyrus, left middle frontal gyrus, and right amygdala/parahippocampal gyrus in the MDD compared to HCL group. Moreover, differential activation to sad and happy faces in AMIC correlated negatively with depression severity within the MDD group. Limitations: Small age-range and cross-sectional nature precluded assessment of development of the AMIC in adolescent depression. Conclusions: Given the role of the IC in integrating bodily stimuli with conscious cognitive and emotional processes, our findings of aberrant AMIC function in adolescent MDD provide a neuroscientific rationale for targeting the AMIC in the development of new treatment modalities.
    Journal of Affective Disorders 01/2016; 178. DOI:10.1016/j.jad.2015.03.012 · 3.38 Impact Factor
    • "Additionally, the main finding of structural alterations in basal-ganglia regions has been shown before in another GAD sample without comorbid depression (Liao et al., 2013). Also, while there was higher GM volume in the putamen and caudate nucleus in this study, the literature reports consistently lower volumes in these structures for major depression (Kempton et al., 2011; Bora et al., 2012a, 2012b). Therefore, it seems unlikely that this result was driven by influence from comorbid depression. "
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    ABSTRACT: Increasing efforts have been made to investigate the underlying pathophysiology of generalized anxiety disorder (GAD), but only limited consistent information is available on gray (GM) and white matter (WM) volume changes in affected adults. Additionally, few studies employed dimensional approaches to GAD pathology. This study compares structural brain imaging data from n=19 GAD subjects and n=24 healthy comparison (HC) subjects, all medication-free and matched on age, sex and education. Separate categorical and dimensional models were employed using voxel-based morphometry for GM and WM. Significantly higher GM volumes were found in GAD subjects mainly in basal ganglia structures and less consistently in the superior temporal pole. For WM, GAD subjects showed significantly lower volumes in the dlPFC. Largely consistent findings in dimensional and categorical models point toward these structural alterations being reliable and of importance for GAD. While lower volume in the dlPFC could reflect impaired emotional processing and control over worry in GAD, basal ganglia alterations may be linked to disturbed gain and loss anticipation as implicated in previous functional GAD studies. As perturbations in anticipation processes are central to GAD, these areas may warrant greater attention in future studies.
    10/2015; DOI:10.1016/j.pscychresns.2015.10.009
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    • "The neurobiological basis of major depressive disorder (MDD) is not fully understood. Extensive previous structural neuroimaging studies had reported volumetric changes in chronic medicated MDD patients at the anterior cingulate cortex (ACC) (Arnone et al., 2012; Du et al., 2012), the thalamus (Kempton et al., 2011; Arnone et al., 2012), the dorsolateral prefrontal cortex (DLPFC) (Bora et al., 2012) and the orbitofrontal cortex (OFC) (Kempton et al., 2011; Arnone et al., 2012). However, these studies usually recruited depressive subjects taking antidepressant medication, and the findings might be confounded by medication effects. "
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    ABSTRACT: Cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment and course of illness in chronic medicated patients. The present study examined cortical thickness in patients with untreated first-episode MDD to elucidate the early pathophysiology of this illness. Here, we examined cortical thickness in patients with first-episode MDD (N=27) and healthy controls (N=27) using an automated surface-based method (in FreeSurfer). By assessing the correlation between caudate volume and cortical thickness at each vertex on the cortical surface, a caudate-cortical network was obtained for each group. Subsequent analysis was performed to assess the effect of anhedonia by the Temporal Experience of Pleasure Scale. We observed increased cortical thickness at the right orbital frontal cortex and the left inferior parietal gyrus in MDD patients compared with healthy controls. Furthermore, morphometric correlational analysis using cortical thickness measurement revealed increased caudate-cortical connectivity in the bilateral superior parietal gyrus in MDD patients. All changes were not related to anhedonia. These preliminary findings may reflect disorder manifestation close to illness onset and may provide insight into the early neurobiology of MDD.
    Psychiatry Research: Neuroimaging 09/2015; 234(1). DOI:10.1016/j.pscychresns.2015.09.014 · 2.42 Impact Factor
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