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

ABSTRACT 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, Sep 26, 2015
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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
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    • "A lower CAR and reduced pACC GMV have also been found in patients with PTSD (Karl et al, 2006; Wessa et al, 2006). The link to major depression is less clear as it has typically been found associated with reduced pACC GMV (Bora et al, 2012) but linked to an increase in the CAR in most (Vreeburg et al, 2009; Lamers et al, 2013) but not all studies (Stetler and Miller, 2005). However, subclinical depressive symptoms in a community sample have been linked to a lower CAR (Dedovic et al, 2010). "
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    ABSTRACT: The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel-based morphometry) magnetic resonance imaging. Across subjects, a smaller CAR was associated with reduced grey matter volume and increased stress-related brain activity in the perigenual ACC, a region which inhibits HPA axis activity during stress that is implicated in risk mechanisms and pathophysiology of stress-related mental diseases. Moreover, functional connectivity between the perigenual ACC and the hypothalamus, the primary controller of HPA axis activity, was associated with the CAR. Our findings provide support for a role of the perigenual ACC in regulating the CAR in humans and may aid future research on the pathophysiology of stress-related illnesses, such as depression, and environmental risk for illnesses such as schizophrenia.Neuropsychopharmacology accepted article preview online, 17 March 2015. doi:10.1038/npp.2015.77.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2015; 40(9). DOI:10.1038/npp.2015.77 · 7.05 Impact Factor
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    • "with these additional covariates included. Since grey matter changes are also seen in depression (Bora et al., 2012) and anxiety disorders (Shang et al., 2014), we performed a final control analysis restricted to the 14 patients without current or precious psychiatric comorbidity and the control group. Here, the group difference remained significant (F(1,35)¼33.794, "
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    ABSTRACT: The cerebellum is connected to extensive regions of the cerebrum, and cognitive deficits following cerebellar lesions may thus be related to disrupted cerebello-cerebral connectivity. Moreover, early cerebellar lesions could affect distal brain development, effectively inducing long-term changes in brain structure and cognitive function. Here, we characterize supratentorial brain structure and cognitive function in 20 adult patients treated for cerebellar tumours in childhood (mean age at surgery: 7.1 years) and 26 matched controls. Relative to controls, patients showed reduced cognitive function and increased grey matter density in bilateral cingulum, left orbitofrontal cortex and the left hippocampus. Within the patient group, increased grey matter density in these regions was associated with decreased performance on tests of processing speed and executive function. Further, diffusion tensor imaging revealed widespread alterations in white matter microstructure in patients. While current ventricle volume (an index of previous hydrocephalus severity it patients) was associated with grey matter density and white matter microstructure in patients, this could only partially account for the observed group differences in brain structure and cognitive function. In conclusion, our results show distal effects of cerebellar lesions on cerebral integrity and wiring, likely caused by a combination of neurodegenerative processes and perturbed neurodevelopment.
    Neuropsychologia 02/2015; 69:218-231. DOI:10.1016/j.neuropsychologia.2015.02.007 · 3.30 Impact Factor
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