Most people could tell you that neglect or abuse during childhood has lasting psychological effects, but it takes rigorous research to explain how that happens and to develop ways to help. That’s the focus of Kevin Bath, a Brown neuroscience researcher who joins the tenure-line ranks as assistant professor of cognitive, linguistic, and psychological sciences this fall.
Bath studies the physical impact of early life stress on brain development and the behavioral consequences of those early experiences. Stress, for example, suppresses both the levels and the activity of brain-derived neurotropic factor, a key chemical in neurodevelopment. Gene mutations and deficits in BDNF are associated with depression and anxiety in both humans and animals.
Ever mindful of the human relevance of the subject, Bath collaborates closely with several medical faculty and departmental colleagues who work with at-risk and affected children, but he also works with mouse models so that he can make detailed observations about behavior, brain structure, and biochemistry that aren’t attainable with people.
“We can see the biological basis in a very controlled setting under very strict conditions and hope this extrapolates out to the much more complex and complicated world of human life,” he said.
In his work, Bath has made some important findings. One is that a common mutation in the human BDNF gene, when recapitulated in mice, leads to the development of anxiety and depressive-like outcomes that mirror the increased risk for these problems in people. Also, as Bath and co-authors showed in Science in 2006, this mutation blunts the mouse response to common anti-depressant treatments, which suggests potential implications for understanding drug-resistant forms of depression if these results translate to humans.
In more recent work, Bath has found that many of the effects of this mutation emerge with age, in that mice develop pathological behavior as they reach adolescence. This has prompted Bath to focus on early development, how experience shapes the developmental profile of BDNF expression, and how adverse experiences, such as stress, may disturb typical development.
Another set of findings suggests that the effects of disturbances in BDNF also impact female behavioral development. While NIH director Francis Collins has lamented that most researchers overlook gender differences in animal models, Bath has made a point of exploring those differences. That work, too, has yielded important results. Previous studies in humans have suggested that mutations in BDNF are associated with anxiety and depression in males but not females. But Bath has shown that female mice with a mutation in the BDNF gene develop anxiety and depressive-like behaviors too, but that these outcomes arrive during adolescence and are highly sensitive to hormonal changes associated with the estrous cycle. That linkage may indicate that this mutation could be involved in mood disturbances associated with post-partum depression, peri-menopausal depression, or pre-menstrual dysthymic disorder.
A research resource
Bath’s research program has turned out to benefit many colleagues. Not long after he arrived at Brown in 2010 (with his wife Dima Amso, assistant professor of cognitive, linguistic, and psychological sciences), he began collaborating with Thomas Serre, an assistant professor in the department who had developed a system to automate the observation and tracking of mouse behavior.
By 2012, with support from the Carney Fund for Innovation, they had advanced the technology and its research applications far enough to open the lab as a research core across Brown’s academic medical center. Now several campus and hospital-based researchers use the lab.
The system allows for long-term observations of behavior in a conventional setting. For a mouse model of a movement disorder, a researcher can use the system to observe over time whether a drug helps the mouse move around better in its daily life.
Bath also facilitates the research of undergraduates in a class he teaches called the “Laboratory in Genes and Behavior.” He teaches mostly juniors and seniors how to design and conduct behavioral experiments and to think about the possible genetic underpinnings. The class’s work has even generated pilot data that he’s worked into his research program.
He also teaches a seminar, “The Neural Bases of Cognition.”
It is clear that although Bath’s work is fundamentally rooted in some serious and tragic issues, he has been enjoying the opportunity to do it within Brown’s close-knit brain science and medical community.
“It’s a great place to be with wonderful colleague and collaborators,” he said.