Unknown,Transcriptomics,Genomics,Proteomics

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Leukocyte gene expression variation as a function of chronic caregiving stress

ABSTRACT: This study explored how chronic stress influences the activity of signaling pathways that regulate inflammation in the human monocyte transcriptome. The sample consisted of 33 adults caring for a family member with glioblastoma, a terminal brain cancer, and 47 control subjects whose lives were free of major stressors. The subjects were assessed on four occasions across an eight-month period. Relative to controls, caregivers’ monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor in monocytes. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys anti-inflammatory signals to monocytes. These transcriptional disparities were not attributable to demographic or behavioral confounds. They also were not attributable to differences in diurnal cortisol output, or the abundance of glucocorticoid receptor expressed by monocytes. In ex vivo studies of monocytes stimulated with the bacterial product lipopolysaccharide, caregivers showed increased production of the pro-inflammatory cytokine interleukin-6, and were less sensitive to cortisol-mediated inhibition of this response. These findings suggest a scenario wherein chronic stressors engender functional changes that hamper monocytes’ capacity to transduce cortisol’s anti-inflammatory signals. These changes occur in parallel with, and perhaps enable, greater inflammatory signaling via nuclear-factor kappa B. The resulting inflammatory milieu could serve as a pathogenic mechanism through which chronic stressors like caregiving accentuate vulnerability to later health problems. series type: Risk prediction Individual differences in basal leukocyte gene expression profiles as a function of chronic caregiving stress Characteristics included in statistical analyses of gene expression data are provided in each sample records. Please note that educational attainment is scored as following; 0=less than high school, 1=high school diploma or equivalent, 2=associate's degree, 3=bachelor's degree, 4=masters degree, 5=doctoral degree

ORGANISM(S): Homo sapiens

SUBMITTER: Steve Cole

PROVIDER: E-GEOD-52319 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Individual differences in basal leukocyte gene expression profiles as a function of child's and parent's perception of family stress, and as a function of parent's psychological well-being. Gene expression profiling was carried out on peripheral blood mononuclear cell mRNA samples collected from 273 individuals (129 parent:child pairs + 15 parent-or-child) who were also assessed on their perceptions of family stress (both parent's and child's perception). Each dyad is labeled by a case ID, with p suffix indicating parent's gene expression profile and c suffix indicating child's gene expression profile. Variations in gene expression are analyzed as a function of both parent's perception of family stress and child's perception of family stress (using UCLA Life Stress Interview, as previously described: Hammen C (1991) Generation of stress in the course of unipolar depression. J Abnorm Psychol 100:555-561; Adrian C, Hammen C (1993) Stress Exposure and Stress Generation in Children of Depressed Mothers. Journal of Consulting and Clinical Psychology 61:354-359; Rudolph KD, Hammen C (1999) Age and gender as determinants of stress exposure, generation, and reactions in youngsters: A transactional perspective. Child Development 70:660-677). Higher values indicate greater levels of subjectively perceived family stress. Additional data are available for 107 parents who completed all 6 subscales of the Psychological Well-Being (PWB) Scale (Ryff CD (1989) Happiness is everything, or is it? Explorations on the meaning of psychological well-being. J. Pers Soc. Psychol 57: 1069-1081), resulting in scores for PWB_Total (average score across all 6 subscales) as well as scores for subscales measuring Purpose in Life (PWB_Purpose), Environmental Mastery (PWB_Environmental_Mastery), Self-Acceptance (PWB_Self_Accept), Autonomy (PWB_Autonomy), Personal Growth (PWB_Growth), Positive Relations with Others (PWB_Relationship). Higher scores indicate greater psychological well being. Also available for those individuals are measures of age (years), male gender (0/1), ethnic group (1=White, 2=Chinese, 3=Indian, 4=Other Asian, 5=Other Ethnicity), Body Mass Index (kg/m^2), heavy alcohol consumption history (0/1), smoking history (0/1), and abundance of 8 mRNA transcripts indicating the relative prevalence of major leukocyte subsets (CD3E, CD3D, CD19, CD4, CD8A, FCGR3A, NCAM1, CD14). key word: Risk prediction

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Leukocyte gene expression variation as a function of chronic caregiving stress

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