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Widespread reductions in gray matter volume in depression.

Grieve SM, Korgaonkar MS, Koslow SH, Gordon E, Williams LM - Neuroimage Clin (2013)

Bottom Line: MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions.Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum.These alterations in volume and cortical thickness were not associated with severity of depressive symptoms.

View Article: PubMed Central - PubMed

Affiliation: The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.

ABSTRACT
Abnormalities in functional limbic-anterior cingulate-prefrontal circuits associated with emotional reactivity, evaluation and regulation have been implicated in the pathophysiology of major depressive disorder (MDD). However, existing knowledge about structural alterations in depression is equivocal and based on cohorts of limited sample size. This study used voxel-based morphometry (VBM) and surface-based cortical thickness to investigate the structure of these circuits in a large and well-characterized patient cohort with MDD. Non-geriatric MDD outpatients (n = 102) and age- and gender-matched healthy control participants (n = 34) provided T1-weighted magnetic resonance imaging data during their baseline visit as part of the International Study to Predict Optimized Treatment for Depression. Whole-brain VBM volumetric and surface-based cortical thickness assessments were performed voxel-wise and compared (at p < 0.05 corrected for multiple comparisons) between the MDD and control groups. MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions. Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum. Focal cortical thinning in the medial orbitofrontal cortex was also observed for the MDD group. These alterations in volume and cortical thickness were not associated with severity of depressive symptoms. The findings demonstrate that widespread gray matter structural abnormalities are present in a well-powered study of patients with depression. The patterns of gray matter loss correspond to the same brain functional network regions that were previously established to be abnormal in MDD, which may support an underlying structural abnormality for these circuits.

No MeSH data available.


Related in: MedlinePlus

Voxel based morphometry volume differences between the MDD and control groups (MDD < controls at p < 0.05 FDR-corrected). The dominant three bilateral clusters are shown in two axial slices (columns 1 & 2), one coronal slice (column 3) and one sagittal slice (column 4) (the location of the axial and coronal slices is marked on the sagittal slice for reference): (top row) cluster 1 — 1a — dorsolateral prefrontal cortex, 1b — lateral orbitofrontal cortex, 1c — precentral gyrus; (middle row) cluster 2 — 2a — gyrus rectus, 1b — anterior cingulate cortex, 1c — posterior cingulate cortex, 1d — precuneus; and (bottom row) cluster 3 — 3a — fusiform gyrus, 3b — inferior temporal gyrus, 3c — middle temporal gyrus and 3d — superior temporal gyrus. Abbreviations: FDR, False Discovery Rate; MDD, Major Depressive Disorder.
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f0005: Voxel based morphometry volume differences between the MDD and control groups (MDD < controls at p < 0.05 FDR-corrected). The dominant three bilateral clusters are shown in two axial slices (columns 1 & 2), one coronal slice (column 3) and one sagittal slice (column 4) (the location of the axial and coronal slices is marked on the sagittal slice for reference): (top row) cluster 1 — 1a — dorsolateral prefrontal cortex, 1b — lateral orbitofrontal cortex, 1c — precentral gyrus; (middle row) cluster 2 — 2a — gyrus rectus, 1b — anterior cingulate cortex, 1c — posterior cingulate cortex, 1d — precuneus; and (bottom row) cluster 3 — 3a — fusiform gyrus, 3b — inferior temporal gyrus, 3c — middle temporal gyrus and 3d — superior temporal gyrus. Abbreviations: FDR, False Discovery Rate; MDD, Major Depressive Disorder.

Mentions: The VBM analysis showed large areas of decreased GM volume in MDD distributed across the brain, with no regions of increased GM volume. The dominant findings were of three large bilateral clusters, with each cluster spanning several contiguous anatomical regions. For convenience, since the three clusters were bilaterally symmetric, the right and left components are referred to below as the same cluster number. These clusters are broadly characterized as follows: (1) the DLPFC (BA 45, 46) with extension inferiorly to the lateral OFC (BA 47) and superiorly to involve the pre/post central gyri (Fig. 1, top row), (2) a large midline region spanning the medial orbitofrontal cortex/posterior gyrus rectus, entire cingulate cortex and the calcarine/lingual gyri (Fig. 1, middle row), and (3) a broad region in the posterior temporal lobe spanning the inferior/middle/superior temporal gyri (Fig. 1, bottom row). These three regions are presented in Table 2, broken down by anatomically distinct regions classified using both AAL and Brodmann descriptors. In addition, several discrete, focal regions of significant GM volume reduction were present, which are presented by lobe in Table 2. These dominant findings are summarized below:


Widespread reductions in gray matter volume in depression.

Grieve SM, Korgaonkar MS, Koslow SH, Gordon E, Williams LM - Neuroimage Clin (2013)

Voxel based morphometry volume differences between the MDD and control groups (MDD < controls at p < 0.05 FDR-corrected). The dominant three bilateral clusters are shown in two axial slices (columns 1 & 2), one coronal slice (column 3) and one sagittal slice (column 4) (the location of the axial and coronal slices is marked on the sagittal slice for reference): (top row) cluster 1 — 1a — dorsolateral prefrontal cortex, 1b — lateral orbitofrontal cortex, 1c — precentral gyrus; (middle row) cluster 2 — 2a — gyrus rectus, 1b — anterior cingulate cortex, 1c — posterior cingulate cortex, 1d — precuneus; and (bottom row) cluster 3 — 3a — fusiform gyrus, 3b — inferior temporal gyrus, 3c — middle temporal gyrus and 3d — superior temporal gyrus. Abbreviations: FDR, False Discovery Rate; MDD, Major Depressive Disorder.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814952&req=5

f0005: Voxel based morphometry volume differences between the MDD and control groups (MDD < controls at p < 0.05 FDR-corrected). The dominant three bilateral clusters are shown in two axial slices (columns 1 & 2), one coronal slice (column 3) and one sagittal slice (column 4) (the location of the axial and coronal slices is marked on the sagittal slice for reference): (top row) cluster 1 — 1a — dorsolateral prefrontal cortex, 1b — lateral orbitofrontal cortex, 1c — precentral gyrus; (middle row) cluster 2 — 2a — gyrus rectus, 1b — anterior cingulate cortex, 1c — posterior cingulate cortex, 1d — precuneus; and (bottom row) cluster 3 — 3a — fusiform gyrus, 3b — inferior temporal gyrus, 3c — middle temporal gyrus and 3d — superior temporal gyrus. Abbreviations: FDR, False Discovery Rate; MDD, Major Depressive Disorder.
Mentions: The VBM analysis showed large areas of decreased GM volume in MDD distributed across the brain, with no regions of increased GM volume. The dominant findings were of three large bilateral clusters, with each cluster spanning several contiguous anatomical regions. For convenience, since the three clusters were bilaterally symmetric, the right and left components are referred to below as the same cluster number. These clusters are broadly characterized as follows: (1) the DLPFC (BA 45, 46) with extension inferiorly to the lateral OFC (BA 47) and superiorly to involve the pre/post central gyri (Fig. 1, top row), (2) a large midline region spanning the medial orbitofrontal cortex/posterior gyrus rectus, entire cingulate cortex and the calcarine/lingual gyri (Fig. 1, middle row), and (3) a broad region in the posterior temporal lobe spanning the inferior/middle/superior temporal gyri (Fig. 1, bottom row). These three regions are presented in Table 2, broken down by anatomically distinct regions classified using both AAL and Brodmann descriptors. In addition, several discrete, focal regions of significant GM volume reduction were present, which are presented by lobe in Table 2. These dominant findings are summarized below:

Bottom Line: MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions.Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum.These alterations in volume and cortical thickness were not associated with severity of depressive symptoms.

View Article: PubMed Central - PubMed

Affiliation: The Brain Dynamics Center, Sydney Medical School, The University of Sydney and Westmead Millennium Institute, Sydney, NSW, Australia.

ABSTRACT
Abnormalities in functional limbic-anterior cingulate-prefrontal circuits associated with emotional reactivity, evaluation and regulation have been implicated in the pathophysiology of major depressive disorder (MDD). However, existing knowledge about structural alterations in depression is equivocal and based on cohorts of limited sample size. This study used voxel-based morphometry (VBM) and surface-based cortical thickness to investigate the structure of these circuits in a large and well-characterized patient cohort with MDD. Non-geriatric MDD outpatients (n = 102) and age- and gender-matched healthy control participants (n = 34) provided T1-weighted magnetic resonance imaging data during their baseline visit as part of the International Study to Predict Optimized Treatment for Depression. Whole-brain VBM volumetric and surface-based cortical thickness assessments were performed voxel-wise and compared (at p < 0.05 corrected for multiple comparisons) between the MDD and control groups. MDD participants had reduced gray matter volume in the anterior cingulate cortex, regions of the prefrontal circuits, including dorsolateral and dorsomedial prefrontal cortices, and lateral and medial orbitofrontal cortices, but not in limbic regions. Additional reductions were observed cortically in the posterior temporal and parieto-occipital cortices and, subcortically in the basal ganglia and cerebellum. Focal cortical thinning in the medial orbitofrontal cortex was also observed for the MDD group. These alterations in volume and cortical thickness were not associated with severity of depressive symptoms. The findings demonstrate that widespread gray matter structural abnormalities are present in a well-powered study of patients with depression. The patterns of gray matter loss correspond to the same brain functional network regions that were previously established to be abnormal in MDD, which may support an underlying structural abnormality for these circuits.

No MeSH data available.


Related in: MedlinePlus