Homework week 3

Homework week 3

by Tene -
Number of replies: 1

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 believe that there are some parallels between the animal study described by Weaver et al and human development. Weaver et al define a critical period of development (the first post-natal week of life) as being the only time that offspring have to develop a defined genetically-linked behavioral response to stress. Depending on the exposure during this first week of life, their stress response into adulthood is defined. In humans, I believe that whether a child is exposed to a nurturing environment of parental contact, holding the child, talking to the child, and environmental security/safety or not affects their developmental outcome. Infants and children raised in high stress, violence, and/or isolated (without human contact) environments are far more likely to have difficulty forming secure relationships and potentially connecting with others in adulthood. However, whereas the animal studies define a critical period as the first week of life, I believe in humans, this period is much longer and may extend from birth through the first few years of life potentially. The behaviors in humans that are most analogous to the maternal licking and grooming displayed in the animal studies include being held/physical touch, being talked to/introduced to language, and consistency of environment/stable parental presence.

 

2.  Provide a brief proposal for a study that would allow you to assess whether epigenetic modifications in humans in response to maternal behavior influence subsequent health of the human (feel free to choose any health or behavioral outcome you think you can do this with, e.g., dementia or depression or smoking). Bonus if you can explain how you would approach this if we assume that the relevant epigenetic changes are tissue specific and occur in the brain. 

A study to asses if epigenetic modifications in response to maternal behavior influence alcohol addiction in humans. This could be an observational study following singleton births. Participants and their parents would be enrolled at the time of birth. A daily log would be kept documenting # of hours per day the child is held by the parent(s), # of hours per day the child is talked/read to by the parent(s), and # of hours per day the child is in the same house/apartment/etc. as the parent(s). Participants would be followed for the first 2 years of life in this fashion. Then, starting at age 25, participants would again be contacted once every 5 years from age 25-40 during which time they would be asked questions about their alcohol consumption patterns.

In order to analyze if the epigenetic changes occur in the brain, the patients, once they reach adult age (the 25yo time point) would have functional MRI (fMRI) brain imaging performed once every 5 years and brain fMRI activity would be monitored when patients are asked questions about alcohol intake and consumption to see which parts of the brain and to what degree these areas show increased or decreased functional activity.

 

3. Gruenewald, in contrast to Weaver, 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. 

The Gruenewald findings of the importance of the cumulative effects of SES adversity on an allostatic load measure are consistent with the Weaver findings. Both researchers conclude that there is a physiologic change that occurs as the result of exposures during childhood development. Taken together, it can be concluded that the critical period of exposure for humans (Gruenewald) is longer than that of rats (Weaver). In addition, the exposure in humans is multifactorial (SES, education, etc) compared to rats (maternal grooming and licking). Both authors however, conclude that there are critical factors to which a child may be exposed during development that have the potential to alter their physiology into adulthood.

 

 4. 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?

Hertzmann and Boyce’s discussion of gene-by-environment interactions influencing developmental trajectories is an interested one. Taking this approach, it is suggested that an underlying genetic predisposition or genetic expression AND an environmental exposure is necessary for the phenotype to be exhibited. In this case, because many genetic variations are grouped among racial/ethnic groups, then those people of the vulnerable group who experience the necessary exposure would have a higher incidence of disease. However, when considering disparities along socioeconomic or geographic categories, since genetic variations are less likely to cluster in these ways, then only those groups with the vulnerable genetic profile would be affected and therefore, it may be less likely to see clustering of phenotype by socioeconomic or geographic stratification.

In reply to Tene

Re: Homework week 3

by Maria Glymour -

Thanks for these comments Tene.

I want to emphasize that GxE interactions can occur and contribute to health disparities even for genetic variants that do not have differential prevalence between groups.  If the environmental exposure is differentially distributed, then it doesn't matter if the frequency of the genetic factors is similar across groups: the people with the high-risk genetic allele will be differentially affected in the disadvantaged group.  

Maria