Coordinate-Based Network Mapping of Brain Structure in Major Depressive Disorder in Younger and Older Adults: A Systematic Review and Meta-Analysis

Zhukovsky, Peter; Anderson, John A. E.; Coughlan, Gillian; Mulsant, Benoit H.; Cipriani, Andrea; Voineskos, Aristotle N.

doi:10.1176/appi.ajp.2021.21010088

Cited by 49 publications

(34 citation statements)

References 57 publications

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“…Modern analysis confirmed previous findings implicating the left and right hippocampus and anterior cingulate in LLD and showed that late onset was significantly associated with widespread structural abnormalities in LLD (Zhukovsky et al 2021 ). Severe LLD showed no hippocampal volume loss but increased WM lesion volume over time, and it appeared that hippocampal atrophy and LLD are independent predictors for increased risk of dementia at long follow up (Gerritsen et al 2022 ).…”

Section: Structural Brain Abnormalities In Lldsupporting

confidence: 86%

“…Late onset of depression was associated with abnormalities in the anterior cingulate (Brodmann area 32) and dorsolateral prefrontal cortex (Brodmann area 9). These data highlight some unique circuitry relevant to LLD, which also may explain some of the risk for cognitive decline (Zhukovsky et al 2021 ). Recent evidence from a multi-site data set showed that LLD patients had alterations in nodal network metrics, which mainly involved the DMN and somatomotor network (SMN).…”

Section: Lld and Brain Circuit Disturbancesmentioning

confidence: 82%

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The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder

Ka¹

2023

J Neural Transm

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Depression is frequent in older individuals and is often associated with cognitive impairment and increasing risk of subsequent dementia. Late-life depression (LLD) has a negative impact on quality of life, yet the underlying pathobiology is still poorly understood. It is characterized by considerable heterogeneity in clinical manifestation, genetics, brain morphology, and function. Although its diagnosis is based on standard criteria, due to overlap with other age-related pathologies, the relationship between depression and dementia and the relevant structural and functional cerebral lesions are still controversial. LLD has been related to a variety of pathogenic mechanisms associated with the underlying age-related neurodegenerative and cerebrovascular processes. In addition to biochemical abnormalities, involving serotonergic and GABAergic systems, widespread disturbances of cortico-limbic, cortico-subcortical, and other essential brain networks, with disruption in the topological organization of mood- and cognition-related or other global connections are involved. Most recent lesion mapping has identified an altered network architecture with "depressive circuits" and "resilience tracts", thus confirming that depression is a brain network dysfunction disorder. Further pathogenic mechanisms including neuroinflammation, neuroimmune dysregulation, oxidative stress, neurotrophic and other pathogenic factors, such as β-amyloid (and tau) deposition are in discussion. Antidepressant therapies induce various changes in brain structure and function. Better insights into the complex pathobiology of LLD and new biomarkers will allow earlier and better diagnosis of this frequent and disabling psychopathological disorder, and further elucidation of its complex pathobiological basis is warranted in order to provide better prevention and treatment of depression in older individuals.

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Section: Structural Brain Abnormalities In Lldsupporting

confidence: 86%

Section: Lld and Brain Circuit Disturbancesmentioning

confidence: 82%

The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder

Ka¹

2023

J Neural Transm

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“…A recently published ALE (activation likelihood estimation) meta-analysis of 17 structural imaging studies with LLD patients reveals the most consistent pattern of decline to be located in the ACC and medial prefrontal cortex compared to age-matched healthy controls. The authors also applied a novel coordinate-based network mapping approach that additionally showed the involvement of frontoparietal control, dorsal attention, and visual networks, particularly in late-onset LLD ( Zhukovsky et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Consistent with structural alterations of networks mediating cognitive control, ( Tadayonnejad et al, 2014 ; Zhukovsky et al, 2021 ), patients with LLD often show severe deficits in executive functions such as cognitive flexibility, planning, response-inhibition or set-shifting ( Herrmann et al, 2007 ; Naismith et al, 2012 ), which led to the conceptualization of the ‘depression executive dysfunction syndrome’ ( Alexopoulos, 2019 ). Cognitive deficits, that also include impairments in processing speed as well as in learning and memory, are associated with a problematic prognostic and clinical perspective ( Alexopoulos et al, 2002 ).…”

Section: Introductionmentioning

confidence: 99%

“…Second, the PE is reflected in prefrontal engagement, particularly in the vmPFC/ventral ACC ( Brassen et al, 2011 ; Mather, 2016 ), which in turn is functionally altered in response to negative information in patients with LLD ( Brassen et al, 2008 ; Brassen et al, 2012 ; Aizenstein et al, 2011 ). Third, the structure of the vmPFC is relatively well preserved in healthy aging ( Fjell et al, 2009 ; Mather, 2016 ), whereas it is one of the key regions that exhibits structural and functional disruption in LLD ( Naismith et al, 2012 ; Zhukovsky et al, 2021 ). Fourth, higher-order cognitive functions appear to be involved, at least in part, in the development of a PE ( Fischer et al, 2010 ; Mather and Knight, 2005 ; Murty et al, 2009 ; Ritchey et al, 2011 ; Roalf et al, 2011 ; Sasse et al, 2014 ) and are needed for flexibly dealing with new challenges ( Friedman and Robbins, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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The need to change: Is there a critical role of midlife adaptation in mental health later in life?

Thams

Brassen

2023

eLife

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Although late-life depression (LLD) is a serious health problem and more common than dementia in people over 60, it is underdiagnosed and undertreated. The cognitive-emotional etiology of LLD is particularly poorly understood. This is in contrast to the now extensive literature from psychology and cognitive neuroscience on the characteristics of emotionally healthy aging. This research consistently shows a change in emotional processing in older adults that is modulated by prefrontal regulation. Lifespan theories explain this change in terms of neurocognitive adaptation to limited opportunities and resources that typically occur in the second half of life. Epidemiological data on an increase in well-being after a low point around age 50 suggest that the majority of people seem quite capable of making this adaptation, even though empirical evidence for a causal modulation of this so called ‘paradox of aging’ and for the role of the midlife dip is still lacking. Intriguingly, LLD is associated with deficits in emotional, cognitive, and prefrontal functions similar to those shown to be crucial for healthy adaptation. Suspected causes of these deficits, such as white matter lesions or affective instability, become apparent as early as midlife when internal and external changes as well as daily challenges set in. Based on these findings, we propose that some individuals who develop depression at older ages may not have been able to successfully implement self-regulatory adaptation at midlife. Here, we review the current evidence and theories on successful aging, the neurobiology of LLD, and well-being across the lifespan. Drawing on recent advances in lifespan theories, emotion regulation research, and cognitive neuroscience, we propose a model of successful versus unsuccessful adaptation that emphasizes the increasing need for implicit habitual control and resource-based regulatory choice during midlife.

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Brain Network Localization of Gray Matter Atrophy and Neurocognitive and Social Cognitive Dysfunction in Schizophrenia

Cheng,

Cai,

Liu

et al. 2025

Biological Psychiatry

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Coordinate-Based Network Mapping of Brain Structure in Major Depressive Disorder in Younger and Older Adults: A Systematic Review and Meta-Analysis

Cited by 49 publications

References 57 publications

The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder

The heterogeneity of late-life depression and its pathobiology: a brain network dysfunction disorder

The need to change: Is there a critical role of midlife adaptation in mental health later in life?

Brain Network Localization of Gray Matter Atrophy and Neurocognitive and Social Cognitive Dysfunction in Schizophrenia

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