Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex White Matter Alterations in Late-Life Depression

Bae, Jae Nam; MacFall, James R.; Krishnan, K. Ranga; Payne, Martha E.; Steffens, David C.; Taylor, Warren D.

doi:10.1016/j.biopsych.2006.03.052

Cited by 264 publications

(221 citation statements)

References 64 publications

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“…In the context of elderly depression, the present findings of anterior and posterior callosal abnormalities in patients vs controls may be consistent with one previous study using magnetization transfer imaging, which reported significantly lower magnetization ratios in the genu and splenium of the corpus callosum (Kumar et al, 2004). On the other hand, two diffusion tensor imaging studies have not found evidence of callosal abnormalities (Bae et al, 2006;Nobuhara et al, 2006) in depressed elders. In addition, one report employing Witelson's segmentation criteria of corpus callosum areas obtained from midsagittal MRI section in a mixed elderly population did not detect an association between callosal atrophy and mood disturbances (Ryberg et al, 2007).…”

Section: Discussionsupporting

confidence: 92%

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

Ballmaier

Kumar

Elderkin‐Thompson

et al. 2007

Neuropsychopharmacol

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There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are regionspecific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age ¼ 68.00, SD75.83), 22 patients with late-onset depression (mean age ¼ 74.50, SD78.09) and 34 elderly control subjects (mean age ¼ 72.38; SD76.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late-vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late-from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late-and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than earlyonset depression, with potentially important implications for research and therapy.

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Section: Discussionsupporting

confidence: 92%

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

Ballmaier

Kumar

Elderkin‐Thompson

et al. 2007

Neuropsychopharmacol

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“…The main finding of our study showed that white matter integrity in the right ALIC is significantly impaired in depressed subjects compared to non-depressed subjects as measured by FA. This finding of decreased integrity of the ALIC in depression complements the growing literature demonstrating white matter alterations in the prefrontal cortex in late-life depression (Taylor et al, 2001;Bae et al, 2006;Shimony et al, 2009;Mettenburg et al, 2012). The decrease of FA in the right ALIC may be explained by a trend towards significant increase in the radial diffusivity (an index of myelin integrity), without significant alterations in axial diffusivity.…”

Section: Discussionsupporting

confidence: 78%

White Matter Tract Integrity of Anterior Limb of Internal Capsule in Major Depression and Type 2 Diabetes

Zhang

Ajilore

Zhan³

et al. 2013

Neuropsychopharmacol

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A number of studies have shown an association between diabetes and depression. However, the underlying mechanisms are still unclear. Previous findings indicate a role for the prefrontal cortex and subcortical gray matter regions in type 2 diabetes and major depressive disorder (MDD). The purpose of this study was to examine the white matter integrity in the fibers that are part of the anterior limb of internal capsule (ALIC) in MDD and diabetic subjects using diffusion tensor imaging tractography. We studied 4 groups of subjects including 1) 42 healthy controls (HC), 2) 28 MDD subjects (MD), 3) 24 patients diagnosed with type 2 diabetes without depression (DC), and 4) 22 patients diagnosed with diabetes and depression (DD). Results revealed significantly decreased fractional anisotropy (FA; P ¼ .021) and a trend towards significant increase in radial diffusivity (RD; P ¼ .078) of the right ALIC in depressed subjects (MD þ DD) compared to non-depressed subjects (HC þ DC). While there were no significant diabetes effects or interactions between depression and diabetes, subjects with high depression ratings and high hemoglobin A1c levels had the lowest mean FA values in the right ALIC. In addition, we found a significant negative correlation between FA of the left ALIC with hemoglobin A1c in diabetic subjects (DC þ DD; P ¼ .016). Our study demonstrated novel findings of white matter abnormalities of the ALIC in depression and diabetes. These findings have implications for clinical manifestations of depression and diabetes as well as their pathophysiology.

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“…Numerous studies in the last two decades have described features of the vascular depression hypothesis in which hyperintense white matter lesions affecting dorsolateral prefrontal and anterior cingulate circuitry are integral to the development of depression in later life and are associated with both executive dysfunction and poor treatment outcome (Bae et al, 2006). This study found evidence of alterations of high energy phosphates, specifically decreased white matter total NTP (with a trend for decreased bNTP predominantly in the white matter), in older depressed subjects compared with older controls.…”

Section: Discussionmentioning

confidence: 99%

³¹Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression

Forester

Harper

Jensen

et al. 2009

Int J Geriat Psychiatry

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SUMMARYIntroduction We investigated tissue specific differences in markers of energy metabolism, including high energy phosphate compounds (beta and total NTP, PCr) and pH, in older adults with depression compared with healthy controls, before and after a 12-week treatment trial of sertraline. Methods Thirteen older adults, age !55, with Major Depressive Disorder (HAMD 17 score of !18) were recruited along with ten age-matched controls. The depression subjects had a pre-and post-treatment 4T 31 P-MRS scan using a threedimensional chemical shift imaging sequence. The extracted brain images were segmented into white matter (WM), gray matter (GM) and CSF. A linear mixed effects model analyzed the effects of pre-treatment and post-treatment depression on phosphorus metabolite concentration estimates (including calculated pH and Mg þþ ). Results Total tissue beta-NTP (À8%, t(18.66) ¼ 3.50; p ¼ 0.0024) and total tissue total NTP (À6%, t(17.41) ¼ 2.68; p ¼ 0.0156) were lower in subjects with geriatric depression compared with healthy controls. Total tissue levels of total-NTP changed significantly with treatment (À2%, t(14.84) ¼ À2.47; p ¼ 0.0259). Total NTP was reduced in the WM, but not the GM, in the pre-treatment depression group (t(51.65) ¼ 4.02; p ¼ 0.0002). Intracellular pH was higher in the GM of subjects with pre-treatment depression (t(1133.84) ¼ À2.10; p ¼ 0.0353) and decreased to approximate control levels after treatment (t(648.86) ¼ À2.53; p ¼ 0.0115). Discussion These findings demonstrate bioenergetic changes including tissue specific differences in 31 P-MRS metabolites in geriatric depression. Decreased white matter total NTP may reflect alterations in white matter function.

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Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex White Matter Alterations in Late-Life Depression

Cited by 264 publications

References 64 publications

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

White Matter Tract Integrity of Anterior Limb of Internal Capsule in Major Depression and Type 2 Diabetes

³¹Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression

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Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex White Matter Alterations in Late-Life Depression

Cited by 264 publications

References 64 publications

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

White Matter Tract Integrity of Anterior Limb of Internal Capsule in Major Depression and Type 2 Diabetes

31Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression

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³¹Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression