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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Available from: Murat Yucel
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    • "Characterization of the neurobiological mechanism underlying major depressive disorder (MDD) is a fundamental goal of biological psychiatry and related neuroscience researches (Mayberg, 2003). The development in neuroimaging analysis techniques has revealed that MDD leads to not only functional, but also structural alterations of specific brain regions (Bora et al., 2012). "
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    ABSTRACT: Background Hippocampal volume loss is known as the best-replicated finding of structural brain imaging studies on major depressive disorder (MDD). Several evidences suggest localized mechanisms of hippocampal neuroplasticity lead the brain imaging studies on the hippocampus and MDD to perform analyses in the subfield level. The aim of this study was to investigate the differences in total and subfield hippocampal volumes, between medication-naïve female MDD patients and healthy controls, through automated segmentation and volumetric methods. Methods Twenty medication-naïve female patients diagnosed with MDD and 21 age-matched healthy controls, underwent T1-weighted structural magnetic resonance scanning. Total volumes of both hippocampi and subfield regions were calculated by the automated procedure for volumetric measures implemented in FreeSurfer and automated segmentation method by Van Leemput et al. Results We observed patients to have significantly smaller volumes of the left hippocampus, subiculum, cornu ammonis 2–3, cornu ammonis 4-dentate gyrus, and right subiculum compared to healthy controls. There were no significant predictors for these subfield region volumes among the illness burden-related parameters including duration of illness, number of depressive episodes, severity of depressive symptoms and memory performances. Limitations Our findings relied on the data of only female participants. Conclusions We found significant volume reductions in several hippocampal subfield regions in medication-naïve female MDD patients. Our results are consistent with neurobiological evidences on hippocampal neuroplasticity in MDD, and replicate previous findings that suggest morphologic changes of hippocampal subfields in MDD patients.
    Full-text · Article · Apr 2016 · Journal of Affective Disorders
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    • "Similar spatial pattern of cortical thinning were recently reported in children prenatally exposed to depression (Sandman et al., 2015). However, the effects ofHamilton et al., 2008;Altshuler et al., 2010), frontal cortex, orbitofrontal cortex, cingulate cortex (Bora et al., 2012), hippocampus (Cole et al., 2011), striatum (Choi et al., 2008;Lorenzetti et al., 2009), and right lateral and left mesial hemispheres (Peterson et al., 2009). Resting state BOLD fMRI studies in depression have found decreased functional connectivity between the anterior cingulate cortex (ACC) and the thalamus (Anand et al., 2005), decreased corticolimbic connectivity (Anand et al., 2007), decreased connectivity between the anterior cingulate cortex and the amygdala (Anand et al., 2009), increased functional connectivity in the dorsomedial prefrontal cortex (DMPFC) (Sheline et al., 2010), and decreased connectivity with the caudate nucleus (Bluhm et al., 2009). "
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    ABSTRACT: Depression is a highly familial and a heritable illness that is more prevalent in the biological offspring of the depressed individuals than in the general population. In a 3-generation, 30-year, longitudinal study of individuals at either a high(HR) or a low(LR) familial risk for depression, we previously showed cortical thinning in the right hemisphere was an endophenotype for the familial risk. In this study, we assessed whether the effects of familial risk were modulated by the serotonin-transporter-linked polymorphic region (5-HTTLPR). We measured cortical thickness using MRI of the brain and associated it with 5-HTTLPR polymorphism in 76 HR and 53 LR individuals. We studied the effects of genotype and gene-by-risk interaction on cortical thickness while controlling for the confounding effects of age and gender, and for the familial relatedness by applying a variance component model with random effects for genotype. The results showed significant effects of gene-by-risk interaction on thickness: The “s” allele was associated with thinner cortex in the LR individuals whereas with thicker cortex in the HR individuals. The opposing gene effects across the two risk groups were likely due to either epistatic effects and/or differing modulation of the neural plasticity by the altered 5-HT signaling in utero.
    Full-text · Article · Jan 2016 · Psychiatry Research: Neuroimaging
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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.
    Full-text · Article · Jan 2016 · Journal of Affective Disorders
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