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Collaborative front emerges in neuroscience research on toxic stress

New studies spurred by collaborative funding put together by BIBS, Prince Neurosciences Institute

Photograph courtesy of Butler Hospital

Stephanie Parade, Ph.D., from Bradley Hospital, left, and Dr. Dr. Audrey Tyrka, from Butler Hospital, who are collaborating on neuroscience research that looks at the biology and the psychology of toxic stress.

By Richard Asinof
Posted 1/11/16
New collaborative research at Butler and Bradley hospitals is looking at both the biology and psychology in understanding the impacts of early life stress and maltreatment in children, linking neuroscience researchers in collaborative efforts.
What are the potential biological connections between early life stress and addiction? What are the similarities between changes in the brain from early life stress and lead poisoning? Can such understanding create a different kind of educational intervention strategy? What is the relationship between inflammation and early life stress? What are the next steps to take in developing a collaborative strategy to reduce toxic stress in Rhode Island? Are there interventions related to the biology of stress that can stop the cascading wave of stress hormones?
The working model of collaboration between hospital systems on neuroscience research poses an interesting question: what other kinds of collaborative interactions can be made to work in the health care delivery system in Rhode Island as an alternative to competition for scant resources? Are there monetary rewards that can become part of the new model of accountable entities that reward collaboration across hospital systems?

PROVIDENCE – The convergence of conversations around the development of collaborative strategies to combat toxic stress in Rhode Island keep expanding, particularly in the way that neuroscience researchers are now collaborating with each other on a number of different studies.

The studies are focused on the ways that early life stress can rewire the brain, working both in animal and human models, capturing the molecular and biological changes that occur as a result, tracking those changes across a broad study of children in Rhode Island, employing different kinds of imaging and tracking, and exploring the way that sympathetic parenting interventions can change the equation.

The neuroscience researchers are sharing results and data, spurred on in part by small pilot program grants for collaborative research made by the Brown Institute for Brain Studies and the Norman Prince Neurosciences Institute.

The major challenge is figuring out how best to integrate the findings of the neuroscience research into the discussions around policy implementation and interventions for toxic stress.

A serendipitous pathway
The pathway that ConvergenceRI has followed in exploring the neuroscience research now underway here in Rhode Island related to toxic stress has been one of extended conversations and serendipity.

An interview with Brown neuroscientist Chris Moore at Brown University about his work on bioluminescent optogenetics led to his recommendation that ConvergenceRI talk to a colleague, Kevin Bath, about Bath’s work on toxic stress. [See links to ConvergenceRI stories below.]

That, in turn, led ConvergenceRI to invite Bath to participate in the Oct. 28, 2015, gathering at Rhode Island College, where he was one of the expert panelists talking about how to develop a collaborative strategy to combat toxic stress in Rhode Island. [See link to ConvergenceRI story below.]

A few weeks later, after a talk given by Brown University President Christina Paxson about unpacking the racial disparities in health, Dr. Nicole Alexander-Scott, the director of the R.I. Department of Health, which had been one of the sponsors of the toxic stress gathering, introduced ConvergenceRI to Dima Amso, a Brown University developmental cognitive neuroscience researcher who directs the Developmental Cognitive Neuroscience Laboratory.

Amso explained that she was conducting research that is seeking to identify the influence of socioeconomic factors and genetics on early brain development in infants and children in Rhode Island.

Do you know Kevin Bath? ConvergenceRI asked.

“Yes, he’s my husband.”

That bit of serendipity led to an interview with Amso [See link to ConvergenceRI story below.]

During the interview, Amso talked about her collaboration with Dr. Audrey Tyrka, related to Tyrka’s work on the relationship between toxic stress in children who have been maltreated and the biological signals of early aging, focused on the shortening of telomores, which are found on DNA and protect the end of the chromosome from deterioration, or from fusion with neighboring chromosomes.

It was not surprising then, when the communications spokeswoman Sara Brandon at Butler Hospital called, asking if ConvergenceRI would be interested in talking with Tyrka, who is the director of Research and the director of the Laboratory for Clinical and Translational Neuroscience at Butler Hospital, and a professor of Psychiatry and Human Behavior at Brown Medical School.

For the interview, Tyrka was joined by Stephanie Parade, Ph.D., who is an assistant professor of research in the Department of Psychiatry and Human Behavior at Brown University, and staff psychologist at Bradley Research Center at Bradley Hospital.

ConvergenceRI: Can you describe the focus of your research?
I have spent a long time studying early life stress as a [precursor] of risk for psychiatric conditions.

ConvergenceRI: I read a paper of yours that looked at the shortening of telomeres and its relationship to early life stress. Can you explain what that is for the lay person?
Telomeres are biomarkers of cellular aging. They are located at the end of chromosomes, they shorten with each cellular division.

We have known for quite some time that things such as cigarette smoke can shorten telomeres. In the last decade, we have identified that psychological and social stress can also shorten telomeres.

We did a study several years ago, in 2009, on early life stress in children and the shortening of telomeres that was linked [to the development of ] cardiovascular disease and cancers, when telomeres get too short.

ConvergenceRI: Can you explain what that means?
When the telomere shortens, it can’t protect the DNA from erroneous replications that can lead to cancer.

We are now replicating that study in both adults and children, looking at maltreated preschool age children.

ConvergenceRI: What do you mean by maltreated?
We have a study of preschool-age children, roughly half of whom have been neglected or abused, working in partnership with DCYF.

All of the children are impoverished, with a sample of roughly 250 kids, studying their environment and experiences, symptoms and biology.

One of the things that we’re looking at is their telomeres.

It is a pilot study in collaboration with Dima Amso, to look at a subset of these children, including neural imaging. The results are very preliminary.

We are also studying a group of 290 healthy adults, without any medical conditions.

We are also looking at mitochrondria and the compensatory response to the impairment of mitochrondrial functions [related to early life stress].

It’s an exciting new area, and we’re planning some research, looking at this in our child study, looking at mitochrondia in humans, from blood and saliva samples.

ConvergenceRI: Are there other ongoing collaborations with neuroscience researchers?
We are also collaborating with Kevin Bath and his mouse models. His work is very exciting; it converges with other findings in neuro-imaging, starting to show the precocious development of neural cells and neural circuits – and precocious puberty.

We are looking to connect precocious development to telomere shortening and to mitochondria [changes].

When you look at the mouse models you can control a lot of things.

ConvergenceRI: What do you think is the best way to bring the work of neuroscientists into the broader policy discussions and interventions around toxic stress?
I really applaud your efforts; it’s really important.

Certainly, one of our aims is to understand the biology, to understand who is most at risk, and to then create better development interventions, preventions and treatments.

One of the other things that’s important particularly for public awareness and the policy makers [is to debunk] the idea that people can pull themselves up by their bootstraps, because the problems they face are embedded in their biology and their DNA.

We’re all responsible for making our lives better.

ConvergenceRI: What are the correlations between the changes in brain development as a result of toxic stress and the damage done by lead poisoning to the brain. Have you looked at their similarities?
I think that’s a really good point. In the child study, the families are all impoverished, there are probably some who have been exposed to high levels of lead.

There are a host of environmental exposures that can lead to cellular damage similar to high lead levels.

An epigenetics expert at Brown, as part of the Rhode Island child study, collected tissue samples from placentas from some 800 mothers, he was looking at heavy metal exposure.

He also collected [clipped] fingernails from children at three weeks to measure heavy metal exposure, looking at potential epigenetic effects.

We haven’t looked at lead poisoning specifically.

ConvergenceRI: What are the outcomes related to parenting and how that can change or mitigate the impacts of stress, in terms of your research?
Simple responsiveness in sensitive parenting, in the mother’s ability to be able to respond in an appropriate and consistent way, such as when an infant responds to being held, [can make a difference.]

[The findings suggest] that more sensitive parenting can serve as a buffer on their social and emotional development, and that adverse effects could be potentially modified by parental behavior.

A child who has experience some kind of maltreatment or trauma, with supportive care, can help facilitate a more positive response.

Another study I have going on right now is related to how domestic violence and maternal depression is linked to behavioral and psychological stress at six months of age.

One of the things were looking at with mothers is their own experience of early adversity, and how that’s linked with the outcomes in the babies’ health and development.

ConvergenceRI: What would like to see happen, in terms of convergence and collaboration?
It’s a little bit tricky to answer, we’re at a point in the clinical world, and the research world, where people are stretched so thin.

It’s a changing environment, with ACOs coming in and with electronic health record systems.

In Rhode Island, there is an incredible burden of mental illness, both on the clinical and research side; funding is terrible.

For the project we did with Dima Amso on cognition and for the one we're proposing Kevin Bath, the funding mechanism is a collaborative grant with the Brown Institute for Brain Science and the Norman Prince Neurosciences Institute.

This grant mechanism encourages work between researchers across departments, both hospital-based and campus-based. In addition, there is a lot of cross-fertilization work between our group, in particular with Dr. Parade and Dr. Ron Seifer, with the Department of Health and other agencies. We are working to further develop these collaborations.

PARADE: There is a lot of cross-fertilization work with the Department of Health and other agencies.


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