Browsing by Subject "Behaviour"

Now showing 1 - 4 of 4
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    Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder
    (Springer Nature, 2022-08-03) Hesam-Shariati, Sonia; Overs, Bronwyn J.; Roberts, Gloria; Toma, Claudio; Watkeys, Oliver J.; Green, Melissa J.; Pierce, Kerrie D.; Edenberg, Howard J.; Wilcox, Holly C.; Stapp, Emma K.; McInnis, Melvin G.; Hulvershorn, Leslie A.; Nurnberger, John I.; Schofield, Peter R.; Mitchell, Philip B.; Fullerton, Janice M.; Medical and Molecular Genetics, School of Medicine
    Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS; n = 41) compared against the bottom two quintiles (Low-BD-PRS; n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. One differentially methylated probe (DMP) (cg00933603; p = 3.54 × 10-7) in VARS2, a mitochondrial aminoacyl-tRNA synthetase, remained significantly hypomethylated after multiple-testing correction. Overall, BD-PRS appeared to broadly impact epigenetic processes, with 1,183 genes mapped to nominal DMPs (p < 0.05); these displayed convergence with genes previously associated with BD, schizophrenia, chronotype, and risk taking. We tested poly-methylomic epigenetic profiles derived from nominal DMPs in two independent samples (n = 54 and n = 82, respectively), and conducted an exploratory evaluation of the effects of family environment, indexing cohesion and flexibility. This study highlights an important interplay between heritable risk and epigenetic factors, which warrant further exploration.
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    Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome
    (Springer Nature, 2022-10-26) Fulton, Sasha L.; Wenderski, Wendy; Lepack, Ashley E.; Eagle, Andrew L.; Fanutza, Tomas; Bastle, Ryan M.; Ramakrishnan, Aarthi; Hays, Emma C.; Neal, Arianna; Bendl, Jaroslav; Farrelly, Lorna A.; Al-Kachak, Amni; Lyu, Yang; Cetin, Bulent; Chan, Jennifer C.; Tran, Tina N.; Neve, Rachael L.; Roper, Randall J.; Brennand, Kristen J.; Roussos, Panos; Schimenti, John C.; Friedman, Allyson K.; Shen, Li; Blitzer, Robert D.; Robison, Alfred J.; Crabtree, Gerald R.; Maze, Ian; Biology, School of Science
    With an incidence of ~1 in 800 births, Down syndrome (DS) is the most common chromosomal condition linked to intellectual disability worldwide. While the genetic basis of DS has been identified as a triplication of chromosome 21 (HSA21), the genes encoded from HSA21 that directly contribute to cognitive deficits remain incompletely understood. Here, we found that the HSA21-encoded chromatin effector, BRWD1, was upregulated in neurons derived from iPS cells from an individual with Down syndrome and brain of trisomic mice. We showed that selective copy number restoration of Brwd1 in trisomic animals rescued deficits in hippocampal LTP, cognition and gene expression. We demonstrated that Brwd1 tightly binds the BAF chromatin remodeling complex, and that increased Brwd1 expression promotes BAF genomic mistargeting. Importantly, Brwd1 renormalization rescued aberrant BAF localization, along with associated changes in chromatin accessibility and gene expression. These findings establish BRWD1 as a key epigenomic mediator of normal neurodevelopment and an important contributor to DS-related phenotypes.
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    Tracking Patterns of Needs During a Telephone Follow-up Program for Family Caregivers of Persons with Stroke
    (Taylor and Francis, 2016-09) Bakas, Tamilyn; Jessup, Nenette M.; McLennon, Susan M.; Habermann, Barbara; Weaver, Michael T.; Morrison, Gwendolyn; Economics, School of Liberal Arts
    Purpose Programs that address stroke family caregiver needs and skill-building are recommended based on the literature and patient care guidelines for stroke rehabilitation. The purpose of this study was to explore patterns of perceived needs and skill-building during a stroke caregiver intervention program. Method Descriptive statistics were used to analyze data from 123 stroke caregivers enrolled in the intervention group of a randomized controlled clinical trial. Caregivers received 8 weekly telephone sessions, with a booster session a month later. At each session, the Caregiver Needs and Concerns Checklist (CNCC) was used to identify and prioritize current needs that were then addressed through skill-building strategies. Results Perceived needs changed over time. Information about stroke was the highest priority need during Session 1. Managing survivor emotions and behaviors was the highest priority for Sessions 2 through 4. Caregivers generally waited until Sessions 5 through 9 to address their own emotional and physical health needs. Physical and instrumental care needs were relatively low but stable across all 9 sessions. Skill-building was consistently high, though it peaked during Sessions 2 and 3. Conclusions Tracking patterns of needs and skill-building suggest appropriate timing for targeting different types of family caregiver support during stroke rehabilitation.
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    Understanding the decision to screen for lung cancer or not: A qualitative analysis
    (Wiley, 2019-12) Burke Draucker, Claire; Rawl, Susan M.; Vode, Emilee; Carter-Harris, Lisa; School of Nursing
    Background Although new screening programmes with low‐dose computed tomography (LDCT) for lung cancer have been implemented throughout the United States, screening uptake remains low and screening‐eligible persons' decisions to screen or not remain poorly understood. Objective To describe how current and former long‐term smokers explain their decisions regarding participation in lung cancer screening. Design Phone interviews using a semi‐structured interview guide were conducted to ask screening‐eligible persons to describe their decisions regarding screening with LDCT. The interviews were transcribed and analysed with conventional content analytic techniques. Setting and participants A subsample of 40 participants (20 who had screened and 20 who had not) were drawn from the sample of a survey study whose participants were recruited by Facebook targeted advertisements. Results The sample was divided into the following five groups based on their decisions regarding lung cancer screening participation: Group 1: no intention to be screened, Group 2: no deliberate consideration but somewhat open to being screened, Group 3: deliberate consideration but no definitive decision to be screened, Group 4: intention to be screened and Group 5: had been screened. Reasons for screening participation decisions are described for each group. Across groups, data revealed that screening‐eligible persons have a number of misconceptions regarding LDCT, including that a scan is needed only if one is symptomatic or has not had a chest x‐ray. A physician recommendation was a key influence on decisions to screen. Discussion and conclusions Education initiatives aimed at providers and long‐term smokers regarding LDCT is needed. Quality patient/provider communication is most likely to improve screening rates.