Conceptualizing Child Health Disparities: A Role for Developmental Neurogenomics AUTHOR: Darlene D. Francis, PhD abstract Department of Psychology, and School of Public Health, Helen Biological, psychological, and social processes interact over a lifetime Wills Neuroscience Institute, University of California, Berkeley, California to influence health and vulnerability to disease. Those interested in KEY WORDS studying and understanding how and why racial/ethnic and social dis- disparities, development, stress, epigenetics parities emerge need to focus on the intersection of these processes. ABBREVIATIONS Recent work exploring molecular epigenetic mechanisms of gene ex- SES—socioeconomic status pression (in humans as well and other mammalian systems) has pro- HPA—hypothalamic-pituitary-adrenal vided evidence demonstrating that the genome is subject to regulation CRF—corticotropin-releasing factor by surrounding contexts (eg, cytoplasmic, cellular, organismic, social). The views presented in this article are those of the author, not The developing stress axis is exquisitely sensitive to regulation by so- the organizations with which she is affiliated. cial forces represented at the level of the epigenome. Old assumptions www.pediatrics.org/cgi/doi/10.1542/peds.2009-1100G about an inert genome are simply incorrect. Epigenetic processes may doi:10.1542/peds.2009-1100G provide the missing link that will allow us to understand how social and Accepted for publication Jul 20, 2009 political conditions, along with individual subjective experiences, can Address correspondence to Darlene D. Francis, PhD, University directly alter gene expression and thereby contribute to observed so- of California, 3210 Tolman Hall, MC 1650, Berkeley, CA 94720- 1650. E-mail: [email protected] cial inequalities in health. Developmental neurogenomics may provide PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). the direct link between the biological and social/psychological worlds. These biological mechanisms of plasticity (at the level of gene expres- Copyright © 2009 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The author has indicated she has no sion and regulation) may play a profound role in how we conceptualize financial relationships relevant to this article to disclose. health inequalities by informing our concepts regarding the somati- zation or embodiment of social inequalities. Pediatrics 2009;124: S196–S202 S196 FRANCIS Downloaded from www.aappublications.org/news by guest on September 29, 2021 SUPPLEMENT ARTICLE Biological, psychological, and social expressed. Epigenetic processes may are transmitted across generations, processes interact over a lifetime to be the key to understanding how alleles are different “versions” of a influence health and vulnerability to forces distal to an individual, such as gene (they exist in 2 forms; dominant disease. A wealth of epidemiologic social and political conditions, along or recessive), and a given genotype is data have documented the relation- with more proximate individual (sub- related to an observable phenotype. ship between socioeconomic status jective) experiences can directly alter This view of genetics has expanded (SES) and health, with low-SES groups gene expression and thereby contrib- dramatically since the early 1900s, yet faring most poorly across multiple ute to observed social inequalities in most scientists who do not work at the health-outcome measures.1 The proba- health. The very recent and powerful level of the genome have had little or bilistic relationship between social new results demonstrating that the no exposure to recent findings in the phenomena and biological vulnerabil- epigenome is subject to environmental field. As a consequence, we remain ity seems to be in direct contrast to the regulation could provide the direct link saddled with the antiquated central commonly shared belief that the fixed between the biological and social or dogma that (1) the flow of information genome (or genotype) plays a larger psychological worlds. Understanding is unidirectional, from genes to envi- “deterministic” role in health out- how genes are differentially regulated ronment, and (2) biological vulnerabil- comes. Indeed, a common approach to by experience will play a profound role ities are classically inherited (in con- understanding disparities by explor- in how we conceptualize health ine- trast to being created by “vulnerable” ing “social” and “biological” factors as qualities by informing our concepts of environments or experience).2 This independent agents divorced from one the somatization or embodiment of so- limited perspective of the genome has another has been extremely limiting. cial inequalities. As our knowledge of had a large influence on the theoreti- The ubiquitous study of gene ϫ envi- epigenetic processes grows, so too cal framework of many academic dis- ronment interactions provides a ready does our capacity to develop early-life ciplines. Table 1 shows the units of example. The assertion is made that interventions to prevent and mitigate study or focus for some classic aca- vulnerability for a given outcome mea- child health disparities. demic disciplines. sure is caused by the interaction of The number of genes predicted (by mo- genes with environments, the classic PLASTICITY OF THE GENOME lecular biologists and geneticists) to nature-versus-nurture debate. Inher- Ecological models and theories of hu- exist in the human genome was far ent in the framing of this equation is an man health that emphasize the inter- higher (ϳ150 000) than the number unacknowledged directionality; genes action of biological, behavioral, and reported (ϳ25 000) in the first draft of come first in time and environments environmental determinants are plen- the Human Genome Project report.3,4 then act on them, resulting in a given tiful. In reality, however, few truly mul- To provide an example, humans and vulnerability. Equally plausible but tilevel research programs or projects the worm Caenorhabditis elegans rarely explored at a molecular or translate at a practical level. For those have a similar number of genes, 20 000 mechanistic level is the hypothesis studying the genome, imagining the to 25 000, despite large differences in that environmental factors are acting ways in which social and societal organism size and complexity. Both on the genome to create differences in forces might alter how genes are reg- species have significantly fewer genes vulnerability (or resilience). The same ulated and expressed seems formida- than the corn plant, which has 40 000.5 variables are factored into the equa- ble. Conversely, those who are inter- Clearly, humans are greater than the tion; however, the function can now be ested in social disparities might find it sum of their genes. The emerging field ϫ described as an environment gene fantastical to assume that a working of epigenetics focuses on the study of interaction. knowledge of biological mechanisms, changes in gene expression that are Recent work exploring molecular epi- such as gene regulation and gene not caused by changes in DNA se- genetic mechanisms of gene expres- expression (ie, genomic plasticity), quence.6 The epigenome consists of sion (in humans and other mammalian might directly inform how they funda- DNA marks and modifications that con- systems) has provided evidence that mentally conceptualize the embodi- trol gene expression.7 The epigenome the genome is subject to regulation by ment of social experience. is innately plastic and can be pro- surrounding contexts (eg, cytoplas- For many social scientists a working grammed or reprogrammed by envi- mic, cellular, nutritional, organismic, knowledge of genetics is limited to a ronmental experiences such as nutri- and sociopolitical). Environments are classical mendelian perspective; genes tion and stress.8–10 These epigenetic capable of regulating how genes are are the physical units of heredity, they mechanisms provide the means PEDIATRICS Volume 124, Supplement 3, November 2009 S197 Downloaded from www.aappublications.org/news by guest on September 29, 2021 TABLE 1 Focus of Classic Academic Disciplines lead to impairments.14 Increased Academic Discipline Focus Environment “wear and tear” on an organism that is Genetics Gene transmission and genotypes Cell nucleus, DNA subjected to repeated challenge or Molecular and Gene-cell regulation System, cell, RNA, and DNA stress might chronically tax the HPA cellular biology Neuroscience Nervous system and neurons Brain axis and ultimately lead to disease vul- Medicine Individual diseases Individual person nerability (both mental and physical). Psychology and social Behavioral and individual differences Individual person or animal and social psychology space (SES, gender, race) DEVELOPMENTAL PLASTICITY OF Sociology Group processes Individuals in groups Ecology Organisms and their environment Physical world THE STRESS AXIS Public health Health protection, promotion, and Populations restoration The quality of early family-life events Public policy Effects of government decisions and Decision-making bodies can influence the health of human, indecision nonhuman primate, and other mam- malian offspring throughout their life- times. Rodent models provide the best through which social experiences can in mammals. This response governs demonstration of parental calibration fundamentally and profoundly alter the metabolic and cardiovascular re- of the developing stress axis in young the regulation and expression of