Health Disparties Forum

Questions Related to Week 4 Readings:

1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”? 

Of course, more research is needed to know for sure whether this mechanism is relevant in humans, but it sure seems like it could be.  It is well known that human babies need touch and interaction with caregivers for appropriate physical, cognitive, and psychological development.  My guess would be that the behaviors most analogous to licking and grooming in rats are holding, patting, stroking, kissing, and talking/singing to the neonate.

1. Gruenewald, in contrast, emphasize the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain. 

I think the Gruenewald findings are somewhat unrelated to the Weaver findings.  Although both are looking at stress in adults, Weaver is talking quite specifically about epigenetic effects of a specific type of interaction during a sensitive window in very early development in a controlled setting, while Gruenewald is attempting to look at cumulative effects on many biomarkers of a much wider range of uncontrolled factors affecting the individual’s environment over longer (but less specified) periods.  The developmental component of Gruenewald is just events during “childhood” or “growing up”, whereas Weaver is quite specific on the importance of narrow developmental windows of time in early life but doesn’t take into account anything about the adult environment.  The predictor variables, measures, and outcomes in the two papers just aren’t similar enough to really argue broadly for or against consistency.

To me the two papers seem mostly like apples and oranges, but the one place where the results do seem a little inconsistent is the way in which Weaver’s findings imply that early adversity necessarily leads to lifelong increased stress, whereas Gruenewald finds that in fact there is less allostatic load for the upwardly mobile than the downwardly mobile.

1. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

I believe that gene-by environment interactions are likely to have significant contributions to racial/ethnic, socioeconomic, and geographic disparities.  It makes sense to me that the way in which genetic expression is affected by individual experience of the environment is what is most salient to outcomes; neither genes nor environment alone can predict outcomes because it is the interaction that is important, and specifically the impact of the environmental experiences on genetic expression.  Since there will be a range of genetic profiles in any population (even if seemingly homogeneous in terms of race/ethnicity, socioeconomic circumstances, or geographic location), the individual impact of the gene-environment interaction will differ.  However, across populations poor environments are likely to lead to a proportionately larger number of individuals with poorer outcomes due to the interaction and thus to disparities in populations.  These disparities also likely tend to get passed down over generations as those parents who are most negatively impacted by the vulnerable gene-poor environment combination are also the most likely to provide stressful prenatal maternal environments for their offspring as well as staying in and/or recreating stressful external environments which will then be experienced by their offspring. 

1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”? 

This mechanism is relevant in human beings although research such as Weaver et al would be impossible to conduct in humans however there is data that in infants, maternal postpartum behavior has long term effects on infant’ physiological, cognitive, social, emotional, behavioral growth.  Immediate post partum is also considered an important period for neonate and maternal bonding.

Behaviors that are analogous to maternal licking and grooming are contact and touch, voice , gazing and response to cues expressed by the infants.

1. Gruenewald, in contrast, emphasizes the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain. 

Gruenwald paper measures multisystem allostatic load with an index of several physiological biomarkers as related to life course socioeconomic adversity. Weaver paper is pertaining to epigenetic changes by maternal behavior in very limited period of time in a controlled experiment. It is pertaining to  brief period of time when the epigenetic changes occur and can be reversed at least in the experiment by demethylation.

Greuenwald paper relied on retrospective assessment of childhood SES and did not have an accurate representation of childhood adversity. It will be impossible from this study to draw any inference about neonatal period and its subsequent effects.

I think the studies are unrelated .

1. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

Genes X environment interaction is an important determinant of racial/ethnic, socioeconomic and geographic dimensions. For examples racial/ethnic and socioeconomic discrimination can accelerate aging process and early onset of diseases and higher mortality. Shortening of chromosomal telomeres is one biological process that is described which leads to early aging and higher age specific mortality.

Another effect of environment to consider is child development.

If for example we take the weaver paper in account and consider the effect of maternal behavior in neonatal period, it has the potential to cause significant developmental problems by epigenetic changes (GxE effect). Other factor to consider is a cumulative exposure to hardships and even environmental exposure during childhood.

Lower socio-economic status is associated with higher basal cortisol level in children ages 6-10 years, which can lead to reduce cognitive trajectory.

Both genes and interaction with environment influence the neurodevelopment and health, and continue to do so over a lifetime.

However, there are other upstream causes of disparities, which include but are not limited access to care, neighborhood and society, policies.

Mariya Samoylova

4/18/15

SES wk 4 homework

1. Weaver et al, maternal behavior effect during specific time in young rat’s life influencing glucocorticoid receptor gene expression. Is this mechanism relevant in humans? If so, what behaviors are most analogous to “maternal licking and grooming”?

This mechanism or something like it is probably relevant to humans. There’s plenty of examples where early childhood experiences influence development and later health outcomes. I think there’s also some evidence suggesting that breast (vs. bottle)-feeding has favorable effect on metabolism.  Maybe very early childhood “licking and grooming” is the unmeasured confounder here. There’s plenty of important confounders in these situations that make it difficult to study the effect of a particular behavior on the expression a particular gene, but it’s a reasonable hypothesis.

Equivalent behaviors would be stroking, kissing, cuddling, cooing.

1. Gruenewald: cumulative effects of SES adversity on a multi-system allostatic load measure. Are these findings consistent with the Weaver findings?

I think one sets the context for the other. A mechanism similar to that in the Weaver findings could be contributing to the Gruenewald findings, though it’s a very small part of a lifetime of experiences. The Weaver findings raise the possibility that there could be a number of environmental and social factors influencing the expression of genes important to physical functioning, that are malleable over the course of one’s lifetime.

The question of whether these critical points are more concentrated in childhood/ can be attributed to maternal care at a specific time point is hard to answer based on the data we have. There’s clearly some effect of childhood SES (and possibly licking/grooming), as subjects in the low -> high group have higher allostatic load vs. high SES.

1. Hertzmann and Boyce: gene-by-environment interactions that influence developmental trajectories. To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

I am convinced by the reasoning of the GxE argument. However, I think that it is susceptible to the proximity trap, and should be discussed with care not to draw away from thinking of the structure of larger ecologic determinants of health outcomes (vs. focusing on mechanisms of their biologic action in the individual).

1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”? 

Infant parental bonding that occurs during the first weeks of an infant’s life has a significant effect on neurodevelopment / HPA axis and stress response. These behaviors include feeding, response to crying, soothing and physical affection, and sensory stimulation (sights, sounds and smells). It’s entirely possible that these behaviors alter long-term gene expression in infants. This is, of course, very difficult to study in humans. In the extreme, however, physical neglect has been correlated with developmental delay. It is probably not known whether human interactions in neonatal life affect the levels of methylation of DNA regulating HPA function.

2. Gruenewald, in contrast, emphasize the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain. 

The Weaver work focuses on the epigenetic effects of stress in the neonatal time period whereas the Gruenewald work focuses on the cumulative physiological effect of stress over a lifetime. It is possible that parental SES influences parent’s ability to spend time bonding with a new infant. Families with low SES may not have access to maternity and paternity leave, food and social support to take time to bond with an infant or may have increased risk of influences such as drugs and alcohol that prevent bonding. This, in turn could lead to direct physiological effects on neurodevelopment during the sensitive window of early infant. This could be viewed as an initial insult that primes the stress response via the HPA  axis functions and sets the HPA response to stress that will be seen through the lifetime. Adversity related to SES across the lifespan may contribute an accumulation of negative effect (allostatic load) which starts during the critical window of neonatal life but cascades throughout life. The allostatic load may be, in some part, determined by the initial HPA priming. The cortisol exposure may even have exponential effects during this and other critical windows of development.

 3. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

Certain allelic variations may predispose people to physical traits but a complex interplay of environmental and genetic factors influence development. For instance, Hertzmann et al give the low MAOA allele as an example. A polymorphism in this allele may predispose individuals to aggressive behavior but maltreatment in childhood was also necessary for individuals with the low MAOA allele to develop aggressive behavior. In this same way, certain socially defined racial or ethnic groups, or groups defined by geographic location, may have also have a clustering of genetic polymorphisms that predispose that group to certain diseases or traits. The physical effects of stress on physiology over a lifetime experienced by people with low SES, the effects of poverty and the experience of discrimination, most likely all contribute to catalyzing the development of disease. The physiologic effects of acute and chronic stress that result from social and environmental stressors, most likely interact with genetics to contribute to disparities between members of socially defined racial categories.

1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”? 

Yes. I think some studies have examined this effect in infants. From what I understand, they suggest Weaver’s findings likely apply to humans as well, in that maternal behavior shapes the stress response system in developing children. I imagine the behaviors most analogous to licking and grooming, and which influence stress reactivity, would be how responsive the caretaker is to the infant when s/he cries. For example, I would think that if the infant experiences a consistently rapid and soothing response (eg holding, bouncing, feeding), it would support the development of low reactivity to stress. Other analogous behaviors might be playing with and talking to the infant.

 2. Gruenewald, in contrast, emphasize the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain. 

I think Gruenewald’s and Weaver’s findings could coexist. Someone could experience Weaver’s epigenetic effects during the early stage of life and develop a reactive stress response system that puts them at greater risk of poor health outcomes. If this person then experienced SES adversity across the life span, this adversity might compound early life effects to produce a particularly high allostatic load (ie Gruenewald’s “always low SES” group). Following Gruenewald’s findings, if this same person were upwardly mobile, they might have had a lower allostatic load, but not as low as it would have had they been of consistently high SES. This suggests that early life adversity has lasting negative effects – which could potentially align with Weaver’s epigenetic mechanism.

 3. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

I think that gene x environment interactions do contribute to major health disparities along all of these dimensions. Race, SES, and geography determine our environmental exposures across the life course. During the developmental stage, these exposures may influence gene expression and our resulting vulnerability to disease – which may be exacerbated by continued negative exposures throughout life. 

1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”? 

I think this model has compelling components that may be applicable to humans. These components are comparable stress mechanisms (HPA axis etc), apparently parental bonding periods, and a long-standing history of work in comparative biology. Given these features, correlation between mouse models and human physiology it is worth at least considering. To me it makes sense that behavior would translate into genes and protein changes, after all, at some level everything we do has a biological component.  That biological component must somehow be encoded on genes and manifested through mechanistic changes in gene expression patterns such as methylation patterns. Though we don’t usually consider it, thoughts, poetry, attachment, love, cuddling, thoughts and actions all must have biological correlations to be manifest in a physical, physiological world. This model gives and explanation (to a point) of how the behaviors of one individual may affect another individual. To me it makes sense that there would also be certain periods of sensitivity to these types of behavior -- periods when the mount brain and physiology is more susceptible to the influential changes of stress or conversely bonding. This builds on the neuroplasticity model and corresponds to ideas of how we as humans learn anything. The behaviors likely most analogous to maternal licking and grooming are probably cuddling and kissing, maybe even stroking, massaging, or general hygiene such as bathing.

1. Gruenewald, in contrast, emphasize the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain. 

Guenewald’s findings suggest that allostatic load is a composite summary of multiple SES adversity experiences and resulting biophysical stressors across the lifespan that can deleteriously affect health. The idea is that AL can accumulate over one’s life as a result of SES, environment exposures, psychosocial exposures, and behavioral exposures to influence biological systems and affect health.  Although in the introduction Guenewald, suggests that this model is entirely and uniquely different that models suggested by Weaver et al. I do not think they are contradictory. Rather, they are functioning on different scales. Whereas Weaver is interested in how social experiences (maternal licking and grooming) are relayed into biological traits through epigenetic mechanisms,  Guenewald et al. are looking at more of a birds eye view as to what the cumulative social and economic realities are manifest in health. Weaver et al. examines just one of the many possible mechanisms that Guenewald describes. The very focused view that Weaver et al. may not express the durability or profound “irreversibility” that Gruenewald is seeing because Weaver et al. are just looking at one of hundreds of possible influential activities that could potentially effect allostatic load.

1. Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

The gene x environment model is a compelling conceptualization for how to model how social experiences can become “biologically embedded” and influence health. It is more specific and well described than simply saying "it’s both genes and environment." But still is a bit "hand wavy" in its attribution to "environmental" and "stress influences" and how adversity changes health directly.  Genes x environment, tries to account for how the skeleton of the genome is mobilized by experiences to give specific health outcomes that shape what we see as the phrenology of SES. For example, the findings that stress can lead to decreased telomere length and ageing brings together baseline (genes) structure, and how that house and structure affect life and how it is lives (ageing). This could be borne out in other diseases as well. Someone may have a baseline risk fo diabetes, but because of social class and access to resources, that biological predilection for diabetes may not become manifest. While the reverse may also be true…that someone may have a genetic predilection that is enhanced by their environmental and social stressors, so fast food, stress, discrimination could enhance their likelihood to develop diabetes and modify its severity. 

1. Weaver et al propose that among rats, maternal behavior towards newborn pups influences their cortisol response to stress via epigenetic mechanisms that change the expression of glucocorticoid receptor gene for the rest of the pup’s life.  They argue that because epigenetic patterns are established at specific developmental periods, there is extreme time sensitivity to when the pup is exposed to particular maternal behaviors (licking and grooming, in this case), and maternal behavior before or after that sensitive period window is not as important.   Do you think this mechanism is relevant in humans?  If so, what behaviors are most analogous to “maternal licking and grooming”? 

I think that the mechanism posited by the others can be applicable to human development. Similar to how fetal development has time-sensitive windows, there may be time-sensitive periods in human development where maternal behaviors are influential. Potential behaviors similar to those studied in the rats in addition to what others have commented on might include breast feeding or act of breast feeding, other forms of mother-child contact such as cradling, that can influence the child’s epigenetics/gene expression.

1. Gruenewald, in contrast, emphasize the cumulative effects of SES adversity on a multi-system allostatic load measure.   Do you think that the Gruenewald findings are consistent, inconsistent, or unrelated to the Weaver findings?  Explain. 

I think the findings from Gruenwald are somewhat different/unrelated to the Weaver findings, in that the Weaver study proposes certain periods are more important than others; the Gruenwald findings posit the effects of negative circumstance over time lead to increased allostatic load, and this can lead to worsened health outcomes. I would think that both theories are plausible and not mutually exclusive of each other; perhaps the Weaver theory might influence one’s level of SES status, and the Gruenwald theory explains how cumulative effects over time alter the individuals’ change in SES situation over time.

1. 3.     Hertzmann and Boyce argue that “it is not genes or environment, nor is it genes and environment, but rather it is gene-by-environment interactions that influence developmental trajectories.”  To what extent do you think that GxE interactions can contribute to major disparities along racial/ethnic, socioeconomic, or geographic dimensions?

Gene by environment interactions likely contribute a lot to disparities along racial/ethnic, SES, or geographic lines. I thought the theory of gene x environment relationships through latency, cumulative effect, and pathway effects are all plausible to explain the widening of disparities. For example, lack of maternal behavior exposure may alter the HPA axis, and alter the individuals ability to deal with stress; followed by cumulative effects of institutional prejudice to increase allostatic load, and the pathways that result in poor education, job, etc, can create a cycle that worsens the disparity between this individual and another of different circumstances.