Complementing the work of colleagues across Marquette, neuroscience research and outreach could help heal generational trauma and bolster resilience in people affected by chronic stress.
By Jesse Lee and Tracy Staedter
“There’s a lot that needs to be healed in Milwaukee,” said Oprah Winfrey, reporting from the city for 60 Minutes on CBS in 2018.
What prompted Winfrey’s visit was research showing that legions of children exposed to conditions common in the city’s poor neighborhoods — hunger, evictions, homelessness, violence, abuse and neglect — struggle with long-term effects of chronic trauma, much like military veterans diagnosed with post-traumatic stress disorder.
The segment built on an award-winning series in the Milwaukee Journal Sentinel, “A Time to Heal” by John Schmid, that chronicled both the economic issues driving generational trauma and the health effects of chronic stress. Schmid deemed trauma a “public health crisis.”
Rather than focusing primarily on end conditions — such as school attainment, substance abuse or post-prison re-entry — as often happens in our communities, Schmid, Winfrey and the experts they consulted cited the need for a more fundamental approach: trauma-informed care that focuses on a person’s experiences before trying to address their behavior. It asks not “What’s wrong with you?” but “What have you endured?”
Since that flurry of media coverage, Milwaukee-based researchers, community leaders, care providers and advocates have explored methods for healing childhood trauma and building resilience. Milwaukee now has an organization marshaling community resources in response to what many call a “21st century epidemic.” Known as SWIM, short for Scaling Wellness in Milwaukee, it was founded in 2018 with a boost from Marquette President Michael R. Lovell and his wife, Amy Lovell, a nonprofit leader in mental health. In 2019, Dr. Emily Mazzulla, clinical assistant professor of psychology, became Marquette’s director of SWIM Collaboration and Innovation, helping Marquette community members plug into the work of the coalition.
“There’s a lot that needs to be healed in Milwaukee.”
Buoyed by the institutional and community-based commitment to trauma response, Marquette faculty members are carving out important roles on the issue. Researchers in the College of Health Sciences have studied the neurobiological effects of stress and trauma in animals — how chronic stress can literally change brain chemistry, creating predispositions for conditions such as addiction and mental illness. Faculty from the college, including Dr. Paul Gasser, associate professor of biomedical sciences, Dr. Robert Wheeler, associate professor of biomedical sciences, and Dr. Marieke Gilmartin, assistant professor of biomedical sciences, are advancing science relating to trauma and sharing their expertise on how chronic stress can change brain chemistry. Their work complements that of other Marquette faculty including Dr. Amy Van Hecke, professor of psychology in the Klingler College of Arts and Sciences and executive co-director of the Next Step Clinic, which she co-founded to address the mental health and developmental needs of Milwaukee’s underserved children and families. She’s joined by Dr. Karisse Callender, assistant professor of counselor education and counseling psychology in the College of Education, who has researched trauma-informed approaches to substance abuse treatment.
In the case of neuroscience researchers, interest in the issue began in the lab — and broadened from there. “As scientists, the interest in this initially came from how stress affects the brain as a biomedical disorder,” says Dr. William E. Cullinan, dean of the College of Health Sciences. “But what it’s really sparked an interest in is addressing this trauma epidemic in different ways.”
Cullinan says that includes forming community partnerships, educating students, and engaging in collaboration with social scientists and clinicians to address trauma by identifying predictors of resilience in communities, which can then lead to better health outcomes. As new collaborations emerge that bridge academic disciplines and engage SWIM partners, hope follows for improved therapies that improve brain function and coping behaviors to bring the healing the city desperately needs.
Stress Hormones and Brain Chemistry
A main research focus among faculty in the College of Health Sciences is to study how stress hormones, in particular cortisol, cause changes in the brain that can “produce functional deficits in terms of how people process information and learn,” says Cullinan.
Existing studies from across the globe already show strong evidence that living in an impoverished environment or one riddled with violence or neglect can have a negative effect on brain function in general and on brain development in children. Two regions are of interest — the prefrontal cortex, which acts as a gatekeeper for impulsive behavior, controlling emotions and decision making, and the amygdala, the brain’s fear center, regulating responses to fear and stress, says Cullinan. In populations affected by chronic stress and trauma, research has shown that the prefrontal cortex literally shrinks, limiting its ability to regulate impulsive behaviors and leading to potentially dangerous decision-making abilities and emotional responses. And unfortunately, the effects of chronic stress, potentially including elevated cortisol levels, are likely inherited.
Armed with this knowledge, scientists from the College of Health Sciences investigate the influence stress hormones have on brain chemistry in animal studies to better understand these neurobiological changes. A recent study from Gasser’s laboratory showed that stress levels of cortisol interact with dopamine, a chemical neurotransmitter in the brain involved in the regulation of reward and motivation, to increase cocaine-seeking behavior. This may explain why people who have suffered trauma may be higher at risk for drug addiction and relapse.
Gasser’s team is also looking at whether cortisol affects cells in the brain called astrocytes, which support the healthy function of brain cells. Preliminary research from his team indicates that chronic cortisol interferes with and changes the functions of astrocytes in the brains of mice, which could provide clues to what’s going on humans.
“If you look at the brain of a person who has hypercortisolism — an overabundance of cortisol — the prefrontal cortex and other areas of the brain are smaller in those individuals,” Gasser says.
Some of those changes are persistent and are caused by alterations in which genes are turned on or off in brain cells. Called epigenetic changes, because they do not alter the DNA but how a DNA sequence is read, these changes may be reversible.
“This is an opportunity for scientific discovery to do the greatest good for our society,” says Wheeler.
Studying the Fear Response
Any living creature, from mouse to human, reacts to threat with a “fight or flight” response — a coordinated activation of physiological and behavioral responses designed for survival. Individuals living in conditions of high-level chronic stress spend more time in this state, which can be detrimental to long-term health. According to Gilmartin, who will become an associate professor with tenure this fall, chronic stress affects brain areas that normally serve to learn about threats and the situations or cues that predict them.
Gilmartin’s lab uses fear conditioning in animal models to better understand how these brain structures — the prefrontal cortex, hippocampus and amygdala — communicate with each other to learn to predict and adaptively respond to threat. The prefrontal cortex and amygdala are partners in adaptive fear responding, with the prefrontal cortex putting the brakes on fear once a threat has passed. However, stress alters the development of these brain areas, she says.
Experiments that Gilmartin conducts lend clues to these interactions. A rat hears a tone and then receives an aversive stimulus. After a few trials, the subject learns to associate the tone with the stimulus and the tone itself triggers a fear response in anticipation of the outcome. Gilmartin has found that neurons in the prefrontal cortex are more active during the tone and in anticipation of the shock, indicating a role in fear memory.
“Early life stress leads to accelerated amygdala development to deal with the constant stress at hand, which seems like a really good and adaptive response,” she says. “But the consequence is that, long term, you get a reduced ability of higher-order prefrontal networks to rein in that response, which ultimately leads to maladaptive fear.”
Predisposed to Illness
It’s not just the developing brain that’s vulnerable to trauma—adult brains are affected as well. Wheeler says trauma has severe and persistent effects well into adulthood and he concurs with Schmid’s characterization of trauma as a public health crisis. Wheeler’s research on animal models focuses on the way stress hormones actually reshape the brain through a process called “regressive neural plasticity.” Neural plasticity is the ability of neurons — transmitter cells within the nervous system or brain — to change or adapt their function and form based on environmental changes. In the case of negative environmental changes, like chronic stress or trauma, the brain undergoes regressive plasticity, losing activity in pathways that a healthy brain uses to regulate both behavior and hormonal release in response to stressors. This regressive plasticity thereby has a negative effect in the regulation of emotional processing and motivational influence, leading to issues like addiction and loss of impulse control. And this plasticity is constant, even into adulthood.
Because the mechanism by which trauma causes regressive neural plasticity is not clear, it’s difficult to show whether trauma-informed care can correct it, he says. But he and other scientists who study regressive neural plasticity think cortisol is a trigger. “A viable theory is that a therapeutic approach that regulates cortisol could be protective,” he says. “If we are correct, then behavioral therapeutic approaches that reduce the hypothalamic pituitary adrenal stress response would be effective in limiting the neuronal damage caused by elevated cortisol.”
In 2018, he started working with an interdisciplinary team that includes fellow College of Health Sciences faculty members Dr. Lucas Torres, professor of psychology, and Dr. Robert Smith, professor of history and director of the Center for Urban Research, Teaching and Outreach, to use their expertise from basic science and their deep knowledge of the area to inform community-wide interventions, including SWIM, in ways that could ultimately help people heal. With researchers from the Medical College of Wisconsin, University of Wisconsin-Milwaukee and the Social Development Commission, Milwaukee’s largest service provider for low-income community members, Wheeler and his colleagues aim to provide research expertise for measuring and analyzing known biological clues. They’ve discussed the possibility of setting up evidence-based research studies and collecting data, such as that from brain imaging and blood tests for cortisol levels to get a better handle on the ways in which concentrated poverty, community violence and structural racism contribute to health disparities and use that knowledge to determine whether interventions are working.
There is a lot of work to be done. Generations of stress and trauma, and the neurobiological effects suffered by people throughout those generations, will not be solved overnight, and the lasting effects of COVID-19 will take years to understand. But taking a multifaceted, community-based approach supported at the highest levels of Marquette leadership will help drive success.
“If we bring lots of people with diverse backgrounds together to tackle this problem, maybe we can make headway in fixing it,” says Wheeler.
