Prevalence of abandoned homes in the neighborhood and thymic function

Prevalence of abandoned homes in the neighborhood and thymic function Biomarker Network Meeting 3/30/16 Elizabeth McClure, MS Lydia Feinstein, PhD Sara Ferrando-Martínez, PhD Manuel Leal, MD PhD Sandro Galea, MD DrPH Allison Aiello, PhD 1

Detroit Neighborhood Environment During the recession, Detroit experienced one of the highest foreclosure rates in the country (Rooney, 2008) 2

Detroit Neighborhood Health Study Population-based cohort study of predominantly African American adults living in Detroit, Michigan 5 study waves & 4 in-home blood draws (2008-2013) Neighborhood assessment and phone survey: health status, social network, trauma, mental health, substance use, and sociodemographics Thymic function assessed in wave 4 3

Study Rationale More work needed to understand biological mechanisms between social context and disease distributions (Steptoe & Marmot, 2002) Immune system is a significant biological factor on the pathway (Steptoe, 2012) Neighborhood characteristics and immune function have not been examined in community-based cohorts 4

Conceptual Model Poor neighborhood quality Poor social cohesion Chronic stress Diminished immune function Negative health outcomes 5

Employment Status Neighborhood Prevalence of Abandoned Homes Thymic Function Gender Age 6

Employment Status Neighborhood Prevalence of Abandoned Homes Social Cohesion Thymic Function Gender Age 7

Thymic Function Thymus is the main organ for de novo naïve T cell production Thymic function plays essential role quality of immune response (Steptoe, 2012) 8

Thymic Function Sensitive to Stress Stress may reduce thymic output of naïve T-cells, evidence largely limited to acute stressors animal studies (Gruver & Sempowski, 2008) Stress-induced thymic atrophy compromises immune system 9

Study Measures Thymic Function Two measures of thymic output of naïve T-cells: 1. Number of signal joint T-cell receptor excision circles (sj-trec) 2. Ratio of signal joint to beta T-cell receptor excision circles (sj/beta-trec ratio) (Ferrando-Martinez et al, 2010) 10

Study Measures Abandoned Homes Proliferation of abandoned homes has become an important source of stress in Detroit Trained raters assessed block group segments presence of abandoned homes Score was aggregated to a percentage in the neighborhood 11

Study Measures Social Cohesion Respondents rated agreement with a series of statements on neighborhood cohesion (1=strongly agree, 5=strongly disagree) Summed for composite score (high score indicates poor cohesion) 12

Analysis 1. Neighborhood prevalence of abandoned homes thymic function 2. Neighborhood prevalence of abandoned homes social cohesion thymic function Two-level linear regressions to estimate variance between and within neighborhoods on sj-trec and sj/beta-trec ratio values Individual respondents nested within neighborhoods 13

Results Descriptive N=277 Measure Description Age Median: 56 (IQR: 47, 67) Female 61% Employed 35% sj-trec Median: 3244.0 (IQR: 1454.7, 7180.2) sj/beta-trec Median: 5.47 (IQR: 1.0, 18.8) Neighborhood with abandoned homes Median: 34 (IQR: 21, 44) 14

Results Abandoned Homes Presence of Abandoned Homes 4-19% 19.1-28% 28.1-39% 39.1-46% 46.1-61% 15

β (95% Confidence Interval) 0.75 Neighborhood Characteristics and Log sjtrec 0.5 0.25 0-0.25-0.5 **p<0.05-0.75 Neighborhood prevalence of abandoned homes main effect Social cohesion main effect** Neighborhood prevalence of abandoned homes, adjusting for social cohesion 16

β (95% Confidence Interval) 0.75 Neighborhood Characteristics and Log sj/beta-trec 0.5 0.25 0-0.25-0.5-0.75 **p<0.05 Neighborhood prevalence of abandoned homes main effect** Social cohesion main effect** Neighborhood prevalence of abandoned homes, adjusting for social cohesion 17

Discussion Findings suggest increases in neighborhood vacancy may influence immune function at the population level Provide support for social cohesion mediating relationship sj/beta-trec measure has been found to be associated with mortality in older adults (Ferrando-Martinez et al, 2013) sjtrec associated with other markers of inflammation in DNHS Further studies needed examining potential stress mechanisms for this link 18

Acknowledgments R01DA022720 (Aiello) R01DA022720-S1 (GWAS supplement)(aiello) R01DA022720-S1 (Phen-X supplement)(aiello) RC1MH088283 (Aiello) 19

Questions? Elizabeth (Libby) McClure, MS Doctoral Student Department of Epidemiology University of North Carolina at Chapel Hill emcclure@unc.edu 20

References Dion ML, Bordi R, Zeidan J, Asaad R, Boulassel MR, Routy JP, Lederman MM, Sekaly RP, Cheynier R. (2007). Slow disease progression and robust therapy-mediated CD4+ T-cell recovery are associated with efficientthymopoiesis during HIV-1 infection. Blood. 109(7):2912-20. Dion ML, Poulin JF, Bordi R, Sylvestre M, Corsini R, Kettaf N, Dalloul A, Boulassel MR, Debré P, Routy JP, Grossman Z, Sékaly RP, Cheynier R. (2004). HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity. 21(6):757-68 Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ,Koup RA. (1998). Changes in thymic function with age and during the treatment of HIV infection. Nature. 396(6712):690-5. Ferrando-Martinez S, Franco JM, Hernandez A, Ordonez A, Gutierrez E, Abad A, Leal M. (2009). Thymopoiesis in elderly human is associated with systemic inflammatory status. Age. 31(2):87-97. Ferrando-Martinez S, Franco JM, Ruiz-Mateos E, Hernandez A, Ordonez A, Gutierrez E, Leal M. (2010). A reliable and simplified sj/beta-trec ratio quantification method for human thymic output measurement. J Immunol Methods. 352(1-2):111-7. Ferrando-Martinez S, Romero-Sanchez MC, Solana R, Delgado J, de la Rosa R, Munoz-Fernandez MA, Ruiz-Mateos E, Leal M. (2013). Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. Age. 35(1):251-9. Goldmann E, Aiello A, Uddin M, Delva J, Koenen KC, Gant LM, Galea S. (2011). Pervasive Exposure to Violence and Posttraumatic Stress Disorder in A Predominantly African American Urban Community: The Detroit Neighborhood Health Study. Journal of traumatic stress, 24(6): 747-751. Gruver AL, Sempowski GD. (2008). Cytokines, leptin, and stress-induced thymic atrophy. J Leukoc Biol. 84(4): 915 923. 21

References (cont.) Kawachi I, Berkman LF. (2003). Neighborhoods and health. New York: Oxford University Press. Lang PO, Govind S, Drame M, Aspinall R. (2013). Measuring the TREC ratio in dried blood spot samples: Intra- and inter-filter paper cards reproducibility. J Immun Meth, 389: 1-8/ Rooney, B. Rust and Sun Belt cities lean '07 foreclosures: Detroit, Stockton and Las Vegas are top activity centers for troubled homeowners, according to new study. 2008 [cited 2016 March 16]; Available from: http://money.cnn.com/2008/02/12/real_estate/realtytrac/index.htm. Steptoe A. (2012). Socioeconomic Status, Inflammation, and Immune Function. In: Segerstrom SC, ed. The Oxford Handbook of Psychoneuroimmunology. New York: Oxford University Press. Steptoe A, Marmot M. (2002). The role of psychobiological pathways in socio-economic inequalities in cardiovascular disease risk. Eur Heart J, 23(1): 13-25. 22

Appendix: More Information on Thymic Function Thymic function must be measured indirectly, as direct measurements are invasive Signal joint T-cell receptor excision circles (sj-trec) are DNA created in T-cells as they pass through the thymus (Douek et al, 1998) Number of sj-trec is a widely used quantification of thymic output (Dion et al, 2007) However, sj-trecs are diluted by proliferation of naïve T cells in peripheral blood (can have a reduction in sjtrecs with no reduction of thymic function) (Dion et al, 2004) Advantage of sj/beta-trec measure is estimation of intrathymic proliferation of T-cells, independent of peripheral activity (Dion et al, 2004; Ferrando-Martinez et al, 2010) 23

Appendix: Results sjtrec and sj/beta-trec 24

Results Main Regressions sjtrec β (95% CI) sj/beta-trec β (95% CI) Unadjusted -0.02 (-0.08, 0.1) -0.1 (-0.3, 0.01) Adjusted for age, sex, employment status -0.1 (-0.9, 0.2) -0.3 (-0.5, -0.09) 25