Amygdala network dysfunction in late-life depression phenotypes: Relationships with symptom dimensions.
Ontology highlight
ABSTRACT:
SUBMITTER: Li W
PROVIDER: S-EPMC4605880 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Publications
Amygdala network dysfunction in late-life depression phenotypes: Relationships with symptom dimensions.
Li Wenjun W Ward B Douglas BD Xie Chunming C Jones Jennifer L JL Antuono Piero G PG Li Shi-Jiang SJ Goveas Joseph S JS
Journal of psychiatric research 20150909
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 re ...[more]
Similar Datasets
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: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:ObjectiveTo identify cognitive phenotypes in late-life depression (LLD) and describe relationships with sociodemographic and clinical characteristics.DesignObservational cohort study.SettingBaseline data from participants recruited via clinical referrals and community advertisements who enrolled in two separate studies.ParticipantsNon-demented adults with LLD (n = 120; mean age = 66.73 ± 5.35 years) and non-depressed elders (n = 56; mean age = 67.95 ± 6.34 years).MeasurementsAll completed a neuropsychological battery, and individual cognitive test scores were standardized across the entire sample without correcting for demographics. Five empirically derived cognitive domain composites were created, and cluster analytic approaches (hierarchical, k-means) were independently conducted to classify cognitive patterns in the depressed cohort only. Baseline sociodemographic and clinical characteristics were then compared across groups.ResultsA three-cluster solution best reflected the data, including "High Normal" (n = 47), "Reduced Normal" (n = 35), and "Low Executive Function" (n = 37) groups. The "High Normal" group was younger, more educated, predominantly Caucasian, and had fewer vascular risk factors and higher Mini-Mental Status Examination compared to "Low Executive Function" group. No differences were observed on other sociodemographic or clinical characteristics. Exploration of the "High Normal" group found two subgroups that only differed in attention/working memory performance and length of the current depressive episode.ConclusionsThree cognitive phenotypes in LLD were identified that slightly differed in sociodemographic and disease-specific variables, but not in the quality of specific symptoms reported. Future work on these cognitive phenotypes will examine relationships to treatment response, vulnerability to cognitive decline, and neuroimaging markers to help disentangle the heterogeneity seen in this patient population.
| S-EPMC9797624 | biostudies-literature
Project description:ObjectiveLate-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined.MethodsIn a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function.ResultsDepressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups.ConclusionConsistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.
| S-EPMC5600662 | biostudies-literature
Project description:While depression is a leading cause of disability, prior investigations of depression have been limited by studying correlates in isolation. A data-driven approach was applied to identify out-of-sample predictors of current depression from adults (N = 217) sampled on a continuum of no depression to clinical levels. The current study used elastic net regularized regression and predictors from sociodemographic, self-report, polygenic scores, resting electroencephalography, pupillometry, actigraphy, and cognitive tasks to classify individuals into currently depressed (MDE), psychiatric control (PC), and no current psychopathology (NP) groups, as well as predicting symptom severity and lifetime MDE. Cross-validated models explained 20.6% of the out-of-fold deviance for the classification of MDEs versus PC, 33.2% of the deviance for MDE versus NP, but -0.6% of the deviance between PC and NP. Additionally, predictors accounted for 25.7% of the out-of-fold variance in anhedonia severity, 65.7% of the variance in depression severity, and 12.9% of the deviance in lifetime depression (yes/no). Self-referent processing, anhedonia, and psychosocial functioning emerged as important differentiators of MDE and PC groups. Findings highlight the advantages of using psychiatric control groups to isolate factors specific to depression.
| S-EPMC8042639 | biostudies-literature
Project description:ImportanceKnowledge gaps persist regarding racial and ethnic variation in late-life depression, including differences in specific depressive symptoms and disparities in care.ObjectiveTo examine racial/ethnic differences in depression severity, symptom burden, and care.Design, setting, and participantsThis cross-sectional study included 25 503 of 25 871 community-dwelling older adults who participated in the Vitamin D and Omega-3 Trial (VITAL), a randomized trial of cancer and cardiovascular disease prevention conducted from November 2011 to December 2017. Data analysis was conducted from June to September 2018.ExposureRacial/ethnic group (ie, non-Hispanic white; black; Hispanic; Asian; and other, multiple, or unspecified race).Main outcomes and measuresDepressive symptoms, assessed using the Patient Health Questionnaire-8 (PHQ-8); participant-reported diagnosis, medication, and/or counseling for depression. Differences across racial/ethnic groups were evaluated using multivariable zero-inflated negative binomial regression to compare PHQ-8 scores and multivariable logistic regression to estimate odds of item-level symptom burden and odds of depression treatment among those with diagnosed depression.ResultsThere were 25 503 VITAL participants with adequate depression data (mean [SD] age, 67.1 [7.1] years) including 12 888 [50.5%] women, 17 828 [69.9%] non-Hispanic white participants, 5004 [19.6%] black participants, 1001 [3.9%] Hispanic participants, 377 [1.5%] Asian participants, and 1293 participants [5.1%] who were categorized in the other, multiple, or unspecified race group. After adjustment for sociodemographic, lifestyle, and health confounders, black participants had a 10% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (rate ratio [RR], 1.10; 95% CI, 1.04-1.17; P < .001); Hispanic participants had a 23% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (RR, 1.23; 95% CI, 1.10-1.38; P < .001); and participants in the other, multiple, or unspecified group had a 14% higher severity level of PHQ-8 scores compared with non-Hispanic white participants (RR, 1.14; 95% CI, 1.04-1.25; P = .007). Compared with non-Hispanic white participants, participants belonging to minority groups had 1.5-fold to 2-fold significantly higher fully adjusted odds of anhedonia (among black participants: odds ratio [OR], 1.76; 95% CI, 1.47-2.11; among Hispanic participants: OR, 1.96; 95% CI, 1.43-2.69), sadness (among black participants: OR, 1.31; 95% CI, 1.07-1.60; among Hispanic participants: OR, 2.09; 95% CI, 1.51-2.88), and psychomotor symptoms (among black participants: OR, 1.77; 95% CI, 1.31-2.39; among Hispanic participants: OR, 2.12; 95% CI, 1.28-3.50); multivariable-adjusted odds of sleep problems and guilt appeared higher among Hispanic vs non-Hispanic white participants (sleep: OR, 1.24; 95% CI, 1.01-1.52; guilt: 1.84; 95% CI, 1.31-2.59). Among those with clinically significant depressive symptoms (ie, PHQ-8 score ≥10) and/or those with diagnosed depression, black participants were 61% less likely to report any treatment (ie, medications and/or counseling) than non-Hispanic white participants after adjusting for confounders (adjusted OR, 0.39; 95% CI, 0.27-0.56).Conclusions and relevanceIn this cross-sectional study, significant racial and ethnic differences in late-life depression severity, item-level symptom burden, and depression care were observed after adjustment for numerous confounders. These findings suggest a need for further examination of novel patient-level and clinician-level factors underlying these associations.
| S-EPMC7325738 | 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:The clinical presentation of late-life depression is highly heterogeneous and likely influenced by the co-presence of somatic diseases. Using a network approach, this study aims to explore how depressive symptoms are interconnected with each other, as well as with different measures of somatic disease burden in older adults. We examined cross-sectional data on 2860 individuals aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, Stockholm. The severity of sixteen depressive symptoms was clinically assessed with the Comprehensive Psychopathological Rating Scale. We combined data from individual clinical assessment and health-registers to construct eight system-specific disease clusters (cardiovascular, neurological, gastrointestinal, metabolic, musculoskeletal, respiratory, sensory, and unclassified), along with a measure of overall somatic burden. The interconnection among depressive symptoms, and with disease clusters was explored through networks based on Spearman partial correlations. Bridge centrality index and network loadings were employed to identify depressive symptoms directly connecting disease clusters and depression. Sadness, pessimism, anxiety, and suicidal thoughts were the most interconnected symptoms of the depression network, while somatic symptoms of depression were less interconnected. In the network integrating depressive symptoms with disease clusters, suicidal thoughts, reduced appetite, and cognitive difficulties constituted the most consistent bridge connections. The same bridge symptoms emerged when considering an overall measure of somatic disease burden. Suicidal thoughts, reduced appetite, and cognitive difficulties may play a key role in the interconnection between late-life depression and somatic diseases. If confirmed in longitudinal studies, these bridging symptoms could constitute potential targets in the prevention of late-life depression.
| S-EPMC8557204 | biostudies-literature
Project description:BackgroundCognitive impairment and depression often co-occur in older adults, but it is not clear whether depression is a risk factor for cognitive decline, a psychological reaction to cognitive decline, or whether changes in depressive symptoms correlate with changes in cognitive performance over time. The co-morbid manifestation of depression and cognitive impairment may reflect either a causal effect or a common cause, depending on the specific symptoms experienced and the cognitive functions affected.MethodThe study sample comprised 1506 community-dwelling older adults aged ⩾65 years from the Longitudinal Aging Study Amsterdam (LASA). We conducted cross-domain latent growth curve analyses to examine longitudinal associations between late-life depression dimensions (i.e. depressed affect, positive affect, and somatic symptoms) and specific domains of cognitive functioning (i.e. processing speed, inductive reasoning, immediate recall, and delayed recall).ResultsPoorer delayed recall performance at baseline predicted a steeper increase in depressed affect over time. Steeper decline in processing speed correlated with a steeper increase in somatic symptoms of depression over time.ConclusionsOur findings suggest a prospective association between memory function and depressed affect, whereby older adults may experience an increase in depressed affect in reaction to poor memory function. Somatic symptoms of depression increased concurrently with declining processing speed, which may reflect common neurodegenerative processes. Our findings do not support the hypothesis that depression symptoms may be a risk factor for cognitive decline in the general population. These findings have potential implications for the treatment of late-life depression and for the prognosis of cognitive outcomes.
| S-EPMC5426346 | biostudies-literature