Bridging late-life depression and chronic somatic diseases: a network analysis
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ABSTRACT:
SUBMITTER: Triolo F
PROVIDER: S-EPMC8557204 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To use novel methods to examine age associations across an integrated brain network in healthy older adults (HOA) and individuals with late-life depression (LLD). Graph theory metrics describe the organizational configuration of both the global network and specified brain regions.Cross-sectional data were acquired. Graph theory was used to explore diffusion tensor imaging-derived white matter networks. Forty-eight HOA and 28 adults with LLD were recruited from the community. Global and local metrics in prefrontal, cingulate, and temporal regions were calculated. Group differences and associations with age were explored.Group differences were noted in local metrics of the right prefrontal and temporal regions, but no significant differences were observed on global metrics. Local (not global) metrics were associated with age differently across groups. For HOA, local metrics across all regions correlated with age, whereas in adults with LLD, correlations were only observed within temporal regions. In keeping with hypothesized regions impacted by LLD, stronger hubs in right temporal regions were observed among HOA, whereas LLD individuals were characterized by robust hubs in frontal regions.We demonstrate widespread age-related changes in local network properties among HOA with different and more restricted local changes in LLD. Although a preliminary analysis, different patterns of correlations in local networks coupled with equivalent global metrics may reflect altered local structural brain networks in patients with LLD.
| S-EPMC4327993 | biostudies-literature
Project description: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.
| S-EPMC5858586 | biostudies-literature
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.
| S-EPMC6880658 | biostudies-literature
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.
| S-EPMC3814948 | biostudies-literature
Project description:Patients with late-life depression (LLD) have a higher incident of developing dementia, especially individuals with memory deficits. However, little is known about the white matter characteristics of LLD with memory deficits (LLD-MD) in the human connectome, especially for the rich-club coefficient, which is an indicator that describes the organization pattern of hub in the network. To address this question, diffusion tensor imaging of 69 participants [15 LLD-MD patients; 24 patients with LLD with intact memory (LLD-IM); and 30 healthy controls (HC)] was applied to construct a brain network for each individual. A full-scale battery of neuropsychological tests were used for grouping, and evaluating executive function, processing speed and memory. Rich-club analysis and global network properties were utilized to describe the topological features in each group. Network-based statistics (NBS) were calculated to identify the impaired subnetwork in the LLD-MD group relative to that in the LLD-IM group. We found that compared with HC participants, patients with LLD (LLD-MD and LLD-IM) had relatively impaired rich-club organizations and rich-club connectivity. In addition, LLD-MD group exhibited lower feeder and local connective average strength than LLD-IM group. Furthermore, global network properties, such as the shortest path length, connective strength, efficiency and fault tolerant efficiency, were significantly decreased in the LLD-MD group relative to those in the LLD-IM and HC groups. According to NBS analysis, a subnetwork, including right cognitive control network (CCN) and corticostriatal circuits, were disrupted in LLD-MD patients. In conclusion, the disease effects of LLD were prevalent in rich-club organization. Feeder and local connections, especially in the subnetwork including right CCN and corticostriatal circuits, were further impaired in those with memory deficits. Global network properties were disrupted in LLD-MD patients relative to those in LLD-IM patients.
| S-EPMC5572942 | biostudies-literature
Project description:ObjectivesLate-life major depressive disorder (MDD) can be conceptualized as a complex dynamic system. However, it is not straightforward how to analyze the covarying depressive symptoms over time in case of sparse panel data. Dynamic time warping (DTW) analysis may yield symptom networks and dimensions both at the patient and group level.MethodsIn the Netherlands Study of Depression in Older People (NESDO) depressive symptoms were assessed every 6 months using the 30-item Inventory of Depressive Symptomatology (IDS) with up to 13 assessments per participant. Our sample consisted of 182 persons, aged ≥ 60 years, with an IDS total score of 26 or higher at baseline. Symptom networks dimensions, and centrality metrics were analyzed using DTW and Distatis analyses.ResultsThe mean age was 69.8 years (SD 7.1), with 69.0% females, and a mean IDS score of 38.0 (SD = 8.7). DTW enabled visualization of an idiographic symptom network in a single NESDO participant. In the group-level nomothetic approach, four depressive symptom dimensions were identified: "core symptoms", "lethargy/somatic", "sleep", and "appetite/atypical". Items of the "internalizing symptoms" dimension had the highest centrality, whose symptom changes over time were most similar to those changes of other symptoms.ConclusionsDTW revealed symptom networks and dimensions based on the within-person symptom changes in older MDD patients. Its centrality metrics signal the most influential symptoms, which may aid personalized care.
| S-EPMC9543072 | biostudies-literature
Project description:The amygdala, a crucial hub of the emotional processing neural system, has been implicated in late-life depression (LLD) pathophysiology. However, the overlapping and diverging amygdala network function abnormalities underlying two clinical LLD phenotypes (i.e., LLD alone and LLD with mild cognitive impairment [LLD-MCI]) are unknown. The aim of this study is to investigate the amygdala functional connectivity (FC) differences between LLD alone, LLD-MCI and healthy controls, and to examine the relationships between amygdala network dysfunction and symptom dimensions. A resting-state functional connectivity magnetic resonance imaging study was conducted to probe amygdala FC in a total of 63 elderly participants (LLD [n = 22], LLD-MCI [n = 15], and age- and gender-equated healthy older adults [n = 26]) using a seed-based voxelwise R-fcMRI approach. LLD-only adults showed increased FC in the posterior default mode and vermis, and diminished connections in the fronto-parietal, salience and temporal areas, relative to controls. The LLD-MCI participants showed diminished FC in the default mode, cognitive control, salience and visual regions, whereas increased FC was limited to lateral parietal cortex compared with healthy controls. The LLD-MCI group also showed diminished FC in the occipital and posterior default mode areas, relative to the LLD-only group. Distinct amygdala FC abnormalities that explain depressive and anxiety symptom severity, and executive functioning were identified. The amygdala FC impairments may distinguish LLD phenotypes. These functional network abnormalities may also explain the heterogeneity seen in the LLD clinical presentations.
| S-EPMC4605880 | biostudies-literature
Project description:Prior studies have demonstrated dysfunctions within the core neurocognitive networks (the executive control [ECN], default mode [DMN] and salience [SN] networks) in late-life depression (LLD). Whether inter-network dysfunctional connectivity is present in LLD, and if such disruptions are associated with core symptom dimensions is unknown. A cross-sectional resting-state functional connectivity magnetic resonance imaging investigation was conducted of LLD (n = 39) and age- and gender-equated healthy comparison (HC) (n = 29) participants. Dual regression independent component analysis approach was used to identify components that represented the ECN, DMN and SN. The intrinsic inter-network connectivity was compared between LLD and HC participants and the relationship of inter-network connectivity abnormalities with dimensional measures was examined. Relative to HC participants, LLD subjects showed decreased inter-network connectivity between the bilateral ECN and default mode subcortical (thalamus, basal ganglia and ventral striatum) networks, and the left ECN and SN insula component; and increased inter-network connections between the left ECN and posterior DMN and salience (dorsal anterior cingulate) network components. Distinct inter-network connectivity abnormalities correlated with depression and anxiety severity, and executive dysfunction in LLD participants. LLD subjects also showed pronounced intra-network connectivity differences within the ECN, whereas fewer but significant DMN and SN disruptions were also detected. Investigating the intrinsic inter-network functional connectivity could provide a mechanistic framework to better understand the neural basis that underlies core symptom dimensions in LLD. Inter-network connectivity measures have the potential to be neuroimaging biomarkers of symptom dimensions comprising LLD, and may assist in developing symptom-specific treatment algorithms.
| S-EPMC5336398 | biostudies-literature
Project description:Job burnout, characterized by feelings of exhaustion, cynicism and reduced personal efficacy, has been defined as a risk state for the development of diseases, but its association with somatic diseases is underexplored. Study participants were 5671 respondents (mean age 44.1 years, range 18-70; 38.6% men) to an online survey of job burnout, using a mobile health web application. Respondents provided data on sociodemographic characteristics, symptoms of burnout, measured with the Maslach Burnout Inventory-General Survey, depressive symptoms, measured with the Profile of Mood States, and 11 categories of somatic diseases. Adjusting for age, sex, educational level, depressive symptoms, and all disease categories included, network analysis showed a significant association of high exhaustion with "high blood pressure" and a category of "other chronic somatic diseases". Low personal efficacy showed a significant association with "chronic lung diseases". In network analysis, clinically relevant depressive symptoms were also significantly associated with "high blood pressure", "other chronic somatic diseases" and "skin diseases". Logistic regression analysis confirmed these associations. Burnout dimensions were significantly associated with an increased risk for somatic diseases, independently of sociodemographic factors and clinically relevant depressive symptoms. This relationship seems particularly evident for the exhaustion dimension of job burnout.
| S-EPMC7595180 | biostudies-literature
Project description:Late-life depression (LLD), compared to depression at a young age, is more likely to have poor prognosis and high risk of progression to dementia. A recent systemic review and meta-analysis of the present antidepressants for LLD showed that the treatment response rate was 48% and the remission rate was only 33.7%, thus implying the need to improve the treatment with other approaches in the future. Recently, agents modulating the glutamatergic system have been tested for mental disorders such as schizophrenia, dementia, and depressive disorder. Ketamine, a noncompetitive NMDA receptor (NMDAR) antagonist, requires more evidence from randomized clinical trials (RCTs) to prove its efficacy and safety in treating LLD. The metabotropic receptors (mGluRs) of the glutamatergic system are family G-protein-coupled receptors, and inhibition of the Group II mGluRs subtypes (mGlu2 and mGlu3) was found to be as effective as ketamine in exerting rapid antidepressant activity in some animal studies. Inflammation has been thought to contribute to depression for a long time. The cytokine levels not only increase with age but also decrease serotonin. Regarding LLD, interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) released in vivo are likely to contribute to the reduced serotonin level. Brain-derived neurotrophic factor (BDNF), a growth factor and a modulator in the tropomyosin receptor kinase (Trk) family of tyrosine kinase receptors, probably declines quantitatively with age. Recent studies suggest that BDNF/TrkB decrement may contribute to learning deficits and memory impairment. In the process of aging, physiological changes in combination with geriatric diseases such as vascular diseases result in poorer prognosis of LLD in comparison with that of young-age depression. Treatments with present antidepressants have been generally unsatisfactory. Novel treatments such as anti-inflammatory agents or NMDAR agonists/antagonists require more studies in LLD. Last but not least, LLD and dementia, which share common pathways and interrelate reciprocally, are a great concern. If it is possible to enhance the treatment of LDD, dementia can be prevented or delated.
| S-EPMC8303929 | biostudies-literature