Nicki Bush, PhD
Examinations of the Environment-Biology interplay across Early Development
Overview of Dr. Bush’s Work: As an HSS Fellow, Dr. Bush is integrating insights from social epidemiology, sociology, clinical psychology, and developmental psychobiology to clarify the etiology of children’s mental and physical health outcomes and subsequent adult health. By integrating these fields and employing longitudinal and multilevel methods, her work investigates the relations among social determinants and health and the biological mediators and moderators of those effects. Her existing work is an initial step towards elucidating the interplay of biology and context in youth development, as physiological systems mature and social environments change.
For example, her finding that low family SES predicts muted responses in young children’s physiological reactivity over time is important, because it highlights how and when social disadvantage alters children’s biological stress response systems and points to early causes for maladaptive mental and physical health trajectories. She intends to expand this work by clarifying the mechanisms by which the SES effect is occurring. More generally, Dr. Bush aims to understand how children’s biology is shaped by a range of social determinants and how these biological changes then might serve as mechanisms for later cognitive (e.g. coping style, failure to anticipate consequences), affective (e.g. depression, anxiety), and/or behavioral (e.g. impulsivity, addiction, violence) responses to stress and adversity. Concurrently, she is expanding her examination of contextual risk effects (e.g. SES, neighborhood, or family adversity) by infusing her models with a new understanding of biology (physiology, genetics, epigenetics) throughout early development, including the prenatal period. She hopes that the training and research collaborations from the HSS fellowship will help her to contribute to the formulation of effective community-based interventions and policies to address health disparities throughout the life course.
Dr. Bush’s academic and clinical training has focused on identifying risks for poor health among children in disadvantaged communities and developing interventions to ameliorate those risks. Her work with foster children, low-income communities, and chronically mentally ill adults revealed the powerful effects of social disadvantage on health. “I was struck simultaneously by individual variation in vulnerability and resiliency to contextual adversity and by the power of social environments to exacerbate or protect individuals from risk.”
Dr. Bush’s early research examined multiple levels of influence within a developmental ecological framework, seeking to advance understanding of how individual differences in temperament modulate the child mental health effects of socioeconomic, parental, and environmental risk (e.g. Bush, Lengua & Colder, in press; Lengua, Bush, Kovacs, Long, Trancik, 2008). Results from Dr. Bush’s dissertation demonstrated that the relation between neighborhood characteristics and adolescent health-risk behaviors (delinquency, smoking, and substance abuse) depended upon adolescents’ temperaments. For example, living in highly stressful, disadvantaged neighborhoods was more strongly related to initial levels of delinquent behavior for youth higher in sensation-seeking and those lower in fearfulness. Further, although attachment to neighborhood predicted a lower likelihood of delinquency, this protection occurred only among youth lower in fear (Bush, Lengua, Hawkins, under review).
Interested in the parallels between temperament and physiological stress responses, Dr. Bush completed a two-year combined postdoctoral fellowship in Health Psychology and Developmental Psychobiology, which focused on the interaction of biology and social context in the prediction of health. Using a novel approach to physiological reactivity data collection with children that may improve the measurement of biological stress responses (Bush, Alkon, Obradovic, Stamperdahl, Boyce, under revision), Dr. Bush and colleagues have examined ways in which children’s biological stress reactivity interacts with social determinants to affect health. For example, they have found that high stress reactivity was associated with more maladaptive outcomes in the context of high adversity but with better adaptation in the context of low adversity—findings that corroborate a reconceptualization of reactivity as biological sensitivity to context by showing that high reactivity can both hinder and promote adaptive functioning (Obradovic, Bush, Stamperdahl, Adler, & Boyce, 2010).
Focus of the Fellowship
Because many adult health problems generally have their origins in childhood, Dr. Bush is developing a program of research focused on examination of bioecological processes across the lifespan, identifying critical periods in development in which an intervention might alter individual trajectories. Using socioeconomically and ethnically diverse longitudinal samples of children, Dr. Bush aims to bridge a macro-level perspective on socioeconomic effects with a micro-level examination of biobehavioral predispositions to psychopathology, focusing on developmental periods in which youth are particularly vulnerable to social contextual influences.
Children’s Physiologic Stress Reactivity. Her current work examines the impact of contextual factors on children’s biological stress responses as a possible mechanism underlying the robust inverse association between SES gradients and health. Preliminary findings from the Peers and Wellness Study (PAWS project) provide the first longitudinal evidence that SES factors induce physiological changes in early childhood. Specifically, low SES predicts muted stress regulatory responses over time for autonomic indices of the sympathetic nervous systems activation, the system that mobilizes biological resources during “fight-or-flight” responses to environmental threat. Understanding determinants of autonomic reactivity is particularly crucial, because its relation to long-term health problems might account for current trends in mental and physical health disparities.
Genetic and Epigenetic Processes. In the Fall of 2010, Dr. Bush will complete data collection on two projects that were funded through pilot grants from the Robert Wood Johnson Foundation. One study examines the ways in which variation in children’s genetic code (polymorphisms) moderates the effect of early experience on children’s mental health. The chances of developing a variety of diseases seem to depend on combinations of both genes and lifestyle, and increasing evidence from adult samples
is revealing that allelic variation can interact with early life stress to predict increased risk for depression and behavior problems. Studying these processes in childhood has the potential to improve understanding of these interactions and illuminate crucial points for intervention. Dr. Bush’s second study examines “epigenetics,” which refers to changes in the way our genes are expressed that result from lifestyle and environment, rather than changes to the DNA code. Her study will test associations between early childhood experiences and epigenetic changes (methylation patterns) with the aim of illuminating biological mechanisms for the effects of context on health. Dr. Bush will also integrate this genetic and epigenetic data with the comprehensive existing PAWS data set of child physiology and health measures to advance understanding of the associations among genetic code, epigenetic patterns, and differences in children’s stress hormones and heart rate reactivity. Research on genetics and epigenetics is accumulating at lightning speed and promises to shed light on questions like: what makes two people who experience the same thing react very differently in their bodies? and in what ways are adult health disparities rooted in early childhood experiences? Studying these processes early in life has great potential to advance understanding of what keeps children healthy and strategies to prevent mental and physical illnesses throughout the life course.
Prenatal Programming of Offspring Health. Dr. Bush’s latest research endeavor reaches far back in development. Converging evidence shows developmental processes in fetal and early postnatal life play a critical role in health risk behaviors and disease states. Moreover, these studies suggest possible common, underlying mechanisms related to maternal nutrition- and maternal-placental-fetal stress-related biology that mediate the effects of adverse intrauterine exposures on the development of brain and peripheral homeostatic and regulatory processes. These, in turn, underlie offspring’s subsequent physiologic reactivity, adiposity, addiction and unhealthy behaviors.
There are only a small number of prospective human studies to date to assess the effects of maternal nutrition, weight gain and stress exposure on offspring’s biological systems, and even fewer longitudinal studies with repeated assessments to capture developmental trajectories. To address this lack of research, UCSF RWJ leadership, Drs. Adler, Epel, and Laraia are conducting a randomized control trial to test the efficacy to two novel wellness interventions compared to a control group to reduce stress and promote optimal gestational weight gain during pregnancy. Through collaboration with this research team, Dr. Bush is piloting a longitudinal study of the prenatal programming effects of maternal stress and eating during pregnancy on offspring physiology, growth, and development. What is particularly exciting about this research is that it allows Dr. Bush to take advantage of the random assignment of maternal participants to assess the effects of reduction in prenatal stress and improvements in maternal weight control on a set of key offspring physical, behavioral and biological outcomes that are directly relevant to future disease risk.
Dr. Bush recently submitted a large-scale grant application to the NIH to fund this research. If funded, she will be able to follow this cohort of offspring prenatally and through their first three years of life. Her research group will examine the prenatal determinants of disease-relevant developmental trajectories, including 1) body composition, weight and BMI, and metabolic function, 2) physiologic stress reactivity and 3) neurobehavioral outcomes that are predictive of future health (child temperament, neuromotor development, and social functioning).