Disrupted orbitomedial prefrontal limbic network in individuals with later-life depression

Harada, Kazuaki; Matsuo, Koji; Nakashima, Mami; Hobara, Teruyuki; Higuchi, Naoko; Higuchi, Fumihiro; Nakano, Masayuki; Otsuki, Koji; Shibata, Tomohiko; Watanuki, Toshio; Matsubara, Takehiro; Fujita, Yusuke; Shimoji, Keigo; Yamagata, Hirotaka; Watanabe, Yoshifumi

doi:10.1016/j.jad.2016.06.031

Cited by 25 publications

(22 citation statements)

References 51 publications

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“…Structural abnormalities in LLD also involve gray matter reduction in the bilateral orbitofrontal and medial frontal cortex, subcallosal gyrus, hippocampus, parahippocampus, amygdala, insula, and anterior cingulate cortex, and cortical thinning and volume reduction in lentiform nucleus (for a review, see [31, 32, 126, 127]), indicating that these alterations within the fronto–striato–limbic network and disrupted orbitomedial prefrontal limbic network play a key role in the pathophysiology of VaDep [47, 128–132]. In very old adults with depression, loss of grey matter volume was most significant in the bilateral insula and anterior cerebral cortex, supporting a cerebrovascular pattern of LLD [133].…”

Section: Resultsmentioning

confidence: 99%

Vascular depression consensus report – a critical update

Aizenstein

Baskys

Boldrini

et al. 2016

BMC Med

187

145

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BackgroundVascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5th edition – a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term “MRI-defined vascular depression”.DiscussionThis diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal–subcortical–limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed.ConclusionThe multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

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Section: Resultsmentioning

confidence: 99%

Vascular depression consensus report – a critical update

Aizenstein

Baskys

Boldrini

et al. 2016

BMC Med

187

145

View full text Add to dashboard Cite

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“…Individuals with LLD vs. HC groups, showed disruption in white matter integrity in frontal-executive (Shimony et al, 2010;Yuan et al, 2010), and corticolimbic tracts (Shimony et al, 2010;Yuan et al, 2010;Harada et al, 2016). However, these studies have also found no significant difference between individuals with LLD and an HC group in other frontal-executive (Shimony et al, 2010;Yuan et al, 2010;Sexton et al, 2012a) and corticolimbic tracts (Yuan et al, 2010;Sexton et al, 2012a).…”

Section: Dwi Studies Using Roi Analysismentioning

confidence: 90%

“…Seven studies compared white matter integrity using ROI analysis of which six compared differences between individuals with LLD and an HC group, and one across individuals with LLD, aMCI, and LLD+aMCI, and an HC group (Li et al, 2014). Additionally, three studies conducted TBSS (Mettenburg et al, 2012;Sexton et al, 2012a;Harada et al, 2016), and tract-specific voxelwise analysis (Li et al, 2014) presented in the section DWI Studies Using TBSS.…”

Section: Dwi Studies Using Roi Analysismentioning

confidence: 99%

Evidence for Structural and Functional Alterations of Frontal-Executive and Corticolimbic Circuits in Late-Life Depression and Relationship to Mild Cognitive Impairment and Dementia: A Systematic Review

et al. 2020

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Depression is a risk factor for developing Alzheimer's disease and Related Dementia (ADRD). We conducted a systematic review between 2008 and October 2018, to evaluate the evidence for a conceptual mechanistic model linking depression and ADRD, focusing on frontal-executive and corticolimbic circuits. We focused on two neuroimaging modalities: diffusion-weighted imaging measuring white matter tract disruptions and resting-state functional MRI measuring alterations in network dynamics in late-life depression (LLD), mild cognitive impairment (MCI), and LLD+MCI vs. healthy control (HC) individuals. Our data synthesis revealed that in some but not all studies, impairment of both frontal-executive and corticolimbic circuits, as well as impairment of global brain topology was present in LLD, MCI, and LLD+MCI vs. HC groups. Further, posterior midline regions (posterior cingulate cortex and precuneus) appeared to have the most structural and functional alterations in all patient groups. Future cohort and longitudinal studies are required to address the heterogeneity of findings, and to clarify which subgroups of people with LLD are at highest risk for developing MCI and ADRD.

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“…Middle-aged and older patients (aged ≥50 years) and healthy participants were recruited according to a previous report 15, 55 . Briefly, patients were recruited from Yamaguchi University Hospital and referred by clinics and hospitals in the area, while healthy control participants (HC) were recruited using advertisements in the community.…”

Section: Methodsmentioning

confidence: 99%

Identification of commonly altered genes between in major depressive disorder and a mouse model of depression

Yamagata

Uchida

Matsuo

et al. 2017

Sci Rep

Self Cite

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The heterogeneity of depression (due to factors such as varying age of onset) may explain why biological markers of major depressive disorder (MDD) remain uncertain. We aimed to identify gene expression markers of MDD in leukocytes using microarray analysis. We analyzed gene expression profiles of patients with MDD (age ≥50, age of depression onset <50) (N = 10, depressed state; N = 13, remitted state). Seven-hundred and ninety-seven genes (558 upregulated, 239 downregulated when compared to those of 30 healthy subjects) were identified as potential markers for MDD. These genes were then cross-matched to microarray data obtained from a mouse model of depression (676 genes, 148 upregulated, 528 downregulated). Of the six common genes identified between patients and mice, five genes (SLC35A3, HIST1H2AL, YEATS4, ERLIN2, and PLPP5) were confirmed to be downregulated in patients with MDD by quantitative real-time polymerase chain reaction. Of these genes, HIST1H2AL was significantly decreased in a second set of independent subjects (age ≥20, age of onset <50) (N = 18, subjects with MDD in a depressed state; N = 19, healthy control participants). Taken together, our findings suggest that HIST1H2AL may be a biological marker of MDD.

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Disrupted orbitomedial prefrontal limbic network in individuals with later-life depression

Cited by 25 publications

References 51 publications

Vascular depression consensus report – a critical update

Vascular depression consensus report – a critical update

Evidence for Structural and Functional Alterations of Frontal-Executive and Corticolimbic Circuits in Late-Life Depression and Relationship to Mild Cognitive Impairment and Dementia: A Systematic Review

Identification of commonly altered genes between in major depressive disorder and a mouse model of depression

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