Dataset Information

Disruption of amygdala-entorhinal-hippocampal network in late-life depression.

ABSTRACT: Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc.

SUBMITTER: Leal SL

PROVIDER: S-EPMC5858586 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Disruption of amygdala-entorhinal-hippocampal network in late-life depression.

Leal Stephanie L SL Noche Jessica A JA Murray Elizabeth A EA Yassa Michael A MA

Hippocampus 20170207 4

Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an e ...[more]

PMID: 28085210

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Project description:Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with medial temporal lobe structural abnormalities. However, the hippocampal functional connectivity (HFC) similarities and differences related to these syndromes when they occur alone or coexist are unclear. Resting-state functional connectivity MRI (R-fMRI) technique was used to measure left and right HFC in 72 elderly participants (LLD [n = 18], aMCI [n = 17], LLD with comorbid aMCI [n = 12], and healthy controls [n = 25]). The main and interactive relationships of LLD and aMCI on the HFC networks were determined, after controlling for age, gender, education and gray matter volumes. The effects of depressive symptoms and episodic memory deficits on the hippocampal functional connections also were assessed. While increased and decreased left and right HFC with several cortical and subcortical structures involved in mood regulation were related to LLD, aMCI was associated with globally diminished connectivity. Significant LLD-aMCI interactions on the right HFC networks were seen in the brain regions critical for emotion processing and higher-order cognitive functions. In the interactive brain regions, LLD and aMCI were associated with diminished hippocampal functional connections, whereas the comorbid group demonstrated enhanced connectivity. Main and interactive effects of depressive symptoms and episodic memory performance were also associated with bilateral HFC network abnormalities. In conclusion, these findings indicate that discrete hippocampal functional network abnormalities are associated with LLD and aMCI when they occur alone. However, when these conditions coexist, more pronounced vulnerabilities of the hippocampal networks occur, which may be a marker of disease severity and impending cognitive decline. By utilizing R-fMRI technique, this study provides novel insights into the neural mechanisms underlying LLD and aMCI in the functional network level.

Project description:Background: Depression and anxiety are the most common comorbid psychiatric disorders in the elderly. Psychiatrists have been reporting worsened depression symptoms and prognosis by comorbid anxiety symptoms. However, it is still unclear how anxiety affects the course of depression in the elderly. The aims of this study are (1) to identify the symptom network in late-life depression (LLD), and (2) to examine the role of anxiety in LLD with a network perspective. Methods: The study analyzed 776 community-based participants who were clinically diagnosed with depression and enrolled in Suwon Geriatric Mental Health Center. Network analysis was used to investigate the relationships between the symptoms of the Montgomery-Åsberg Depression Rating Scale (MADRS). The depression sample was divided into groups of low and high anxiety according to the Beck Anxiety Index. Propensity score matching (PSM) was used to minimize the effects of depression severity on the network. Network comparison test (NCT) were carried out to compare the global connectivity, global strength, and specific edge strength between the two subgroups. Results: Reported sadness, pessimistic thinking, and suicidal ideation are the core symptoms of LLD in terms of node strength. The MADRS sum score [mean (SD) 28.10 (9.19) vs 20.08 (7.11); P < .01] was much higher in the high anxiety group. The NCT before PSM showed the high anxiety group had significantly higher global strength (P < .01). However, the NCT after PSM did not reveal any statistical significance both in global structure (P = .46) and global strength (P = .26). A comparison between centrality indices showed a higher node strength of vegetative symptoms in the high anxiety group and this also remained after PSM. Conclusion: Based on the statistical analysis, anxiety worsens the severity of depression in the elderly. However, NCT after PSM revealed comorbid anxiety does not change the global structure and strength of the depression symptom network. Therefore, anxiety may affect LLD in a way of worsening the severity, rather than changing psychopathology. Additionally, the study revealed the centrality of vegetative symptoms was low in LLD but increased substantially in patients with comorbid anxiety.

Dataset Information

Disruption of amygdala-entorhinal-hippocampal network in late-life depression.

Publications

Disruption of amygdala-entorhinal-hippocampal network in late-life depression.

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