Dataset Information

Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

ABSTRACT: Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we performed genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n = 6,884) from three independent cohorts, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Health and Retirement Study (HRS), and the Indiana Memory and Aging Study (IMAS). Gene-based meta-analysis identified genome-wide significant associations (ANGPT4 and FAM110A, q-value = 0.026; GRM7-AS3 and LRFN5, q-value = 0.042). Pathway analysis revealed enrichment of association in 105 pathways, including multiple pathways related to ERK/MAPK signaling, GSK3 signaling in bipolar disorder, cell development, and immune activation and inflammation. GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder. The ERK/MAPK signaling pathway is a known target of antidepressant drugs and has important roles in neuronal plasticity, and GSK3 signaling has been previously implicated in Alzheimer's disease and as a promising therapeutic target for depression. Our results warrant further investigation in independent and larger cohorts and add to the growing understanding of the genetics and pathobiology of depressive symptoms in aging and neurodegenerative disorders. In particular, the genes and pathways demonstrating association with depressive symptoms may be potential therapeutic targets for these symptoms in older adults.

SUBMITTER: Nho K

PROVIDER: S-EPMC4398648 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

Nho Kwangsik K Ramanan Vijay K VK Horgusluoglu Emrin E Kim Sungeun S Inlow Mark H MH Risacher Shannon L SL McDonald Brenna C BC Farlow Martin R MR Foroud Tatiana M TM Gao Sujuan S Callahan Christopher M CM Hendrie Hugh C HC Niculescu Alexander B AB Saykin Andrew J AJ

Journal of Alzheimer's disease : JAD 20150101 4

Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we performed genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n = 6,884) from thre ...[more]

PMID: 25690665

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Project description:Older adults are more susceptible to higher inflammatory levels and depression. Moreover, diet may influence inflammation as well as depression but no previous study examined whether inflammatory dietary patterns are related to depression in an older population. To investigate the longitudinal association between inflammatory dietary patterns (using reduced rank regression (RRR)) and depressive symptoms in a population sample of Italian older adults.We included 827 participants (aged?65years) at baseline in 1998. Follow-up measurements were collected after 3, 6 and 9years. We used RRR to identify inflammatory dietary patterns at baseline. The Centre for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms by using continuous scores and depression by using a cut-off point (CES-D?20).We identified two inflammatory dietary patterns using different sets of response variables. Dietary pattern I was related to inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor ? and was characterized by high intakes of refined grains, sweet snacks, pasta and rice. After full adjustment for confounders, no longitudinal association was found when comparing extreme quartiles of this dietary pattern and depressive symptoms (Q1vs Q4, model 4: B=0.04, 95% CI: -0.06, 0.13) or depression (Q1vs Q4, model 4: OR=0.90, 95% CI: 0.55, 1.45). Dietary pattern II was related to inflammatory markers CRP, IL-18, IL-1?, IL-1 receptor antagonist and was characterized by high intakes of pasta, sugar-sweetened beverages, processed meat and chocolate and sweets. When comparing extreme quartiles, this dietary pattern was not longitudinally associated with depressive symptoms (Q1vs Q4, model 4: B=-0.04, 95% CI: -0.13, 0.05) but an inverse association was found for depression (Q1vs Q4, model 4: OR=0.56, 95% CI: 0.40, 0.94).Our study does not support the hypothesis that dietary patterns linked to inflammatory markers are associated with higher depressive symptoms and higher depression incidence. However, dietary intake in our population of older adults was quite homogeneous which makes it difficult to show clear associations.

Project description:BackgroundThe move away from investigating mental disorders as whole using sum scores to the analysis of symptom-level interactions using network analysis has provided new insights into comorbidities. The current study explored the dynamic interactions between depressive and anxiety symptoms in older Chinese adults with diabetes mellitus (DM) and identified central and bridge symptoms in the depression-anxiety network to provide potential targets for prevention and intervention for depression and anxiety.MethodsThis study used a cross-sectional design with data from the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A regularized partial correlation network for depressive and anxiety symptoms was estimated based on self-reported scales completed by 1685 older adults with DM aged 65 years or older. Depressive and anxiety symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) and the Seven-Item Generalized Anxiety Disorder Scale (GAD-7), respectively. Expected influence (EI) and bridge expected influence (BEI) indices were calculated for each symptom.ResultsAccording to cutoff scores indicating the presence of depression and anxiety, the prevalences of depression and anxiety in our sample were 52.9% and 12.8%, respectively. The comorbidity rate of depression and anxiety was 11.5%. The six edges with the strongest regularized partial correlations were between symptoms from the same disorder. "Feeling blue/depressed", "Nervousness or anxiety", "Uncontrollable worry", "Trouble relaxing", and "Worry too much" had the highest EI values. "Nervousness or anxiety" and "Everything was an effort" exhibited the highest BEI values.ConclusionCentral and bridge symptoms were highlighted in this study. Targeting these symptoms may be effective in preventing the comorbidity of depressive and anxiety symptoms and facilitate interventions in older Chinese adults with DM who are at risk for or currently have depressive and anxiety symptoms.

Dataset Information

Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

Publications

Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

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