Hostname: page-component-8448b6f56d-wq2xx Total loading time: 0 Render date: 2024-04-24T16:24:33.470Z Has data issue: false hasContentIssue false

Is serotonin transporter genotype associated with epigenetic susceptibility or vulnerability? Examination of the impact of socioeconomic status risk on African American youth

Published online by Cambridge University Press:  17 January 2014

Steven R. H. Beach*
Affiliation:
University of Georgia
Gene H. Brody
Affiliation:
University of Georgia
Man Kit Lei
Affiliation:
University of Georgia
Sangjin Kim
Affiliation:
University of Georgia
Juan Cui
Affiliation:
University of Georgia
Robert A. Philibert
Affiliation:
University of Iowa
*
Address correspondence and reprint requests to: Steven R. H. Beach, Center for Family Research, University of Georgia, 1095 College Station Road, Athens, GA 30602-4527; E-mail: srhbeach@uga.edu.

Abstract

We hypothesized that presence of the short allele in the promoter region of the serotonin transporter would moderate the effect of early cumulative socioeconomic status (SES) risk on epigenetic change among African American youth. Contrasting hypotheses regarding the shape of the interaction effect were generated using vulnerability and susceptibility frameworks and applied to data from a sample of 388 African American youth. Early cumulative SES risk assessed at 11–13 years based on parent report interacted with presence of the short allele to predict differential methylation assessed at age 19. Across multiple tests, a differential susceptibility perspective rather than a diathesis–stress framework best fit the data for genes associated with depression, consistently demonstrating greater epigenetic response to early cumulative SES risk among short allele carriers. A pattern consistent with greater impact among short allele carriers also was observed using all cytosine nucleotide–phosphate–guanine nucleotide sites across the genome that were differentially affected by early cumulative SES risk. We conclude that the short allele is associated with increased responsiveness to early cumulative SES risk among African American youth, leading to epigenetic divergence for depression-related genes in response to exposure to heightened SES risk among short allele carriers in a “for better” or “for worse” pattern.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Battaglia, M., Ogliari, A., Zanoni, A., Citterio, A., Pozzoli, U., Giorda, R., et al. (2005). Influence of the serotonin transporter promoter gene and shyness on children's cerebral responses to facial expressions. Archives of General Psychiatry, 62, 8594. doi:10.1001/archpsyc.62.1.85 CrossRefGoogle ScholarPubMed
Beach, S. R. H., Brody, G. H., Lei, M. K., Kim, S., Cui, J., & Philibert, R. A. (2013). Effects of cumulative early socio-economic stress on epigenetic reprogramming and depression among African American young adults. Unpublished manuscript, University of Georgia.Google Scholar
Beevers, C. G., Wells, T. T., Ellis, A. J., & McGeary, J. E. (2009). Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli. Journal of Abnormal Psychology, 118, 670681. doi:10.1037/a0016198 Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis–stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908. doi:10.1037/a0017376 Google Scholar
Boyce, W. T., & Ellis, B. J. (2005). Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and functions of stress reactivity. Development and Psychopathology, 17, 271301. doi:10.1017/S0954579405050145 Google Scholar
Bradley, S. L., Dodelzon, K., Sandhu, H. K., & Philibert, R. A. (2005). Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription. American Journal of Medical Genetics, 136B, 5861. doi:10.1002/ajmg.b.30185 Google Scholar
Braveman, P. A., Cubbin, C., Egerter, S., Willaims, D. R., & Pamuk, E. (2010). Socioeconomic disparities in health in the United States: What the patterns tell us. American Journal of Public Health, 1000, S186S196. doi:10.2105/AJPH.2009.166082 Google Scholar
Brody, G. H., Beach, S. R. H., Chen, Y. F., Obasi, E., Philibert, R. A., Kogan, S. M., et al. (2011). Perceived discrimination, serotonin transporter linked polymorphic region status, and the development of conduct problems. Development and Psychopathology, 23, 617627. doi:10.1017/S0954579411000046 Google Scholar
Brody, G. H., Murry, V. M., Gerrard, M., Gibbons, F. X., Molgaard, V., McNair, L. D., et al. (2004). The Strong African American Families program: Translating research into prevention programming. Child Development, 75, 900917. doi:10.1111/j.1467-8624.2004.00713.x CrossRefGoogle ScholarPubMed
Carver, C. S., Johnson, S. L., & Joormann, J. (2008). Serotonergic function, two-mode models of self-regulation, and vulnerability to depression: What depression has in common with impulsive aggression. Psychological Bulletin, 134, 912943. doi:10.1037/a0013740 CrossRefGoogle ScholarPubMed
Carver, C. S., Johnson, S. L., Joormann, J., LeMoult, J., & Cuccaro, M. L. (2011). Childhood adversity interacts separately with 5-HTTLPR and BDNF to predict lifetime depression diagnosis. Journal of Affective Disorders, 132, 8993. doi:10.1016/j.jad.2011.02.001 Google Scholar
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509527. doi:10.1176/appi.ajp.2010.09101452 Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386389.CrossRefGoogle ScholarPubMed
Champagne, D. L., Bagot, R. C., van Hasselt, F., Ramakers, G., Meaney, M. J., de Kloet, E. R., et al. (2008). Maternal care and hippocampal plasticity: Evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. Journal of Neuroscience, 28, 60376045.Google Scholar
Chen, E., Miller, G. E., Walker, H. A., Arevalo, J. M., Sung, C. Y., & Cole, S. W. (2008). Genome-wide transcriptional profiling linked to social class in asthma. Thorax, 64, 3843. doi:10.1136/thx.2007.095091 CrossRefGoogle ScholarPubMed
Cole, S. W. (2011). Social regulation of human gene expresssion. Current Directions in Psychological Science, 18, 132137. doi:10.1111/j.1467-8721.2009.01623.x Google Scholar
Conger, R. D., Wallace, L. E., Sun, Y., Simons, R. L., McLoyd, V. C., & Brody, G. H. (2002). Economic pressure in African American families: A replication and extension of the family stress model. Developmental Psychology, 38, 179193. doi:10.1037/0012-1649.38.2.179 Google Scholar
Crişan, L. G., Pană, S., Vulturar, R., Heilman, R. M., Szekely, R., Drugă, B., et al. (2009). Genetic contributions of the serotonin transporter to social learning of fear and economic decision making. Social Cognitive and Affective Neuroscience, 4, 399408. doi:10.1093/scan/nsp019 Google Scholar
Davies, M. N., Volta, M., Podsley, R., Lumon, K., Dixon, A., Lovestone, S., et al. (2012). Functional annotation of the human brain methylome identifies tissue specific epigenetic variation across brain and blood. Genome Biology, 13, R43. doi:10.1186/gb-2012-13-6-r43 Google Scholar
Dressler, W. W., Oths, K. S., & Gravlee, C. C. (2005). Race and ethnicity in public health research: Models to explain health disparities. Annual Review of Anthropology, 34, 231252. doi:10.1146/annurev.anthro.34.081804.120505 CrossRefGoogle Scholar
Eckhardt, F., Lewin, J., Cortese, R., Rakyan, V. K., Attwood, J., Burger, M., et al. (2006). DNA methylation profiling of human chromosomes 6, 20 and 22. Nature Genetics, 38, 13781385. doi:10.1038/ng1909 Google Scholar
Evans, G. W. (2003). A multimethodological analysis of cumulative risk and allostatic load among rural children. Developmental Psychology, 39, 924933. doi:10.1037/0012-1649.39.5.924 Google Scholar
Evans, G. W., Chen, E., Miller, G., & Seeman, T. (2012). How poverty gets under the skin: A life course perspective. In Maholmes, V. & King, R. B. (Eds.), The Oxford handbook of poverty and child development. New York: Oxford University Press.Google Scholar
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., et al. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences, 102, 1060410609. doi:10.1073/pnas.0500398102 Google Scholar
Hariri, A. R., Drabant, E. M., Munoz, K. E., Kolachana, B. S., Mattay, V. S., Egan, M. F., et al. (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry, 62, 146–152. Retrieved from http://archpsyc.ama-assn.org/cgi/content/abstract/62/2/146 Google Scholar
Hariri, A. R., & Holmes, A. (2006). Genetics of emotional regulation: The role of the serotonin transporter in neural function. Trends in Cognitive Science, 10, 182191. doi:10.1016/j.tics.2006.02.011 Google Scholar
Heinz, A., Braus, D. F., Smolka, M. N., Wrase, J., Puls, I., Hermann, D., et al. (2005). Amygdala–prefrontal coupling depends on a genetic variation of the serotonin transporter. Nature Neuroscience, 8, 2021. doi:10.1038/nn1366 Google Scholar
Isenberg, N., Silbersweig, D., Engelien, A., Emmerich, S., Malavade, K., Beattie, B., et al. (1999). Linguistic threat activates the human amygdala. Proceedings of the National Academy of Sciences, 19, 10456–10459. Retrieved from http://www.pnas.org/content/96/18/10456.abstract Google Scholar
Kanehisa, M., & Goto, S. (2000). KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research, 28, 2730. doi:10.1093/nar/28.1.27 CrossRefGoogle ScholarPubMed
Kim, S., & Brody, G. H. (2005). Longitudinal pathways to psychological adjustment among Black youth living in single-parent households. Journal of Family Psychology, 19, 305313. doi:10.1037/0893-3200.19.2.305 Google Scholar
Kinnally, E. L., Capitanio, J. P., Leibel, R., Deng, L., LeDuc, C., Haghighi, F., et al. (2010). Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes, Brain, and Behavior, 9, 575582.Google Scholar
Koenen, K. C., Uddin, M., Chang, S.-C., Aiello, A. E., Wildman, D. E., Goldman, E., et al. (2011). SLC6A4 methylation modifies the effect of the nunber of traumatic events on risk for posttraumatic stress disorder. Depression and Anxiety, 28, 639647. doi: 10.1002/da.20825 Google Scholar
Maholmes, V., & King, R. B. (2012). The Oxford handbook of poverty and child development. New York: Oxford University Press.Google Scholar
Muthén, L. K., & Muthén, B. O. (2002). How to use a Monte Carlo study to decide on sample size and determine power. Structural Equation Modeling, 4, 599620.Google Scholar
Osinsky, R., Reuter, M., Küpper, Y., Schmitz, A., Kozyra, E., Alexander, N., et al. (2008). Variation in the serotonin transporter gene modulates selective attention to threat. Emotion, 8, 584588. doi:10.1037/a0012826 CrossRefGoogle ScholarPubMed
Plume, J. M., Beach, S. R. H., Brody, G. H., & Philibert, R. A. (2012). A cross-platform genome-wide comparison of the relationship of promoter DNA methylation to gene expression. Frontiers in Genetics: Epigenomics, 3, article 12. doi:10.3389/fgene.2012.00012 Google Scholar
Proctor, B. D., & Dalaker, J. (2003). Poverty in the United States: 2002 (Current Population Reports, P60-222). Washington, DC: US Bureau of the Census. Retrieved from http://www.dlc.org/documents/Census_2002_Poverty.pdf Google Scholar
Risch, N., Herell, R., Lehner, T., Liang, K. L., Eaves, L., Hoh, J., et al. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression. Journal of the American Medical Association, 23, 24622471. doi:10.1001/jama.2009.878 CrossRefGoogle Scholar
Roissman, G. I., Newman, D. A., Fraley, R. C., Haltigan, J. D., Groh, A. M., & Haydon, K. C. (2012). Distinguishing differential susceptibility from diathesis–stress: Recommendations for evaluating interaction effects. Development and Psychopathology, 24, 389409. doi:10.1017/S0954579412000065 Google Scholar
Rollins, B., Martin, M. V., Morgan, L., & Vawter, M. P. (2010). Analysis of whole genome biomarker expression in blood and brain. American Journal of Medical Genetics, 153B, 919936. doi:10.1002/ajmg.b.31062 Google Scholar
Rutter, M. L. (1993). Resilience: Some conceptual considerations. Journal of Adolescent Health, 14, 626631. doi:10.1016/1054-139X(93)90196-V Google Scholar
Sameroff, A. J. (1989). Models of developmental regulation: The environtype. In Cicchetti, D. (Ed.), The emergence of a discipline: Rochester symposia on developmental psychopathology (Vol. 1, pp. 4168). Hillsdale, NJ: Erlbaum.Google Scholar
Shumay, E., Logan, J., Volkow, N. D., & Fowler, J. S. (2012). Evidence that the methylation state of monamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men. Epigenetics, 7, 11511160. doi. 10.4161/epi.21976 Google Scholar
Starfield, B., Robertson, J., & Riley, A. W. (2002). Social class gradients and health in childhood. Ambulatory Pediatrics, 2, 238246.Google Scholar
Szyf, M., & Bick, J. (2013). DNA methylation: A mechanism for embedding early life experiences in the genome. Child Development, 84, 4957. doi:10.1111/j.1467-8624.2012.01793.x Google Scholar
Trollope, A. F., Gutierrez-Mecinas, M., Mifsud, K. R., Collins, A., Saunderson, E. A., & Reul, J. M. (2011). Stress, epigenetic control of gene expression and memory formation. Experimental Neurology. Advance online publication. doi:10.1016/j.expneurol.2011.03.022 Google Scholar
Tung, J., Barreiro, L. B., Johnson, Z. P., Hansen, K. D., Michopoulos, V., Toufexis, D., et al. (2012). Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proceedings of the National Academy of Sciences, 109, 64906495. doi:10.1073/pnas.1202734109 Google Scholar
Unternaehrer, E., Luers, P., Mill, J., Demster, E., Meyer, A. H., Staehli, S., et al. (2012). Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Translational Psychiatry, 2, e150.Google Scholar
Vijayendran, M., Cutrona, C., Beach, S. R. H., Brody, G. H., Russell, D., & Philibert, R. A. (2012). The relationship of the serotonin transporter (SLC6A4) extra long variant to gene expression in an African American sample. American Journal of Medical Genetics, 159B, 611612. doi:10.1002/ajmg.b.32054 Google Scholar
Werner, E. E., & Smith, R. S. (1982). Vulnerable but invincible: A study of resilient children. New York: McGraw–Hill.Google Scholar
Wilson, W. J. (1987). The truly disadvantaged: The inner city, the underclass, and public policy. Chicago: University of Chicago Press.Google Scholar
Zeeberg, B., Feng, W., Wang, G., Wang, M. D., Fojo, A. T., Sunshine, M., et al. (2003). GoMiner: A resource for biological interpretation of genomic and proteomic data. Genome Biology, 4, 18.Google Scholar