Inside ºÚÁÏÉç: Uncovering the Biology of Resilience — in the Brain, Gut, and Skin
Resilience has become a buzzword as a predictor of success in work, school, and life. This condition of mental toughness encompasses the qualities that enable a person who suffers hardship(s) to recover and thrive.
Martha Farah
"Resilience is a timeless topic because major stressors have a way of working themselves into human life, whether by losing your job and becoming homeless, being a victim of violent crime, losing a parent at a young age, fighting in battle, and so forth," said Martha Farah, Walter H. Annenberg Professor in Natural Sciences, director of the Center for ºÚÁÏÉç & Society at the University of Pennsylvania, and moderator of a ºÚÁÏÉç 2021 press conference titled, “Uncovering the Biological Blueprint of Stress Resilience."
Psychiatric disorders including mood disorders can be common after trauma — but not everyone experiences them. Neuroscientists are beginning to hone in on where and how these differences occur in the nervous system in order to help analyze, and perhaps promote, resilience.
Assessing the Skin-to-Brain Circuit in Social Touch
Social touch is critical for a whole host of skills, including cognition and attachment, during both childhood and adulthood. Social distancing during the COVID-19 pandemic caused a widespread dearth of social touch for many individuals quarantining alone. But how is touch experienced as different from other forms of non-human contact, and how does the brain process it?
Melanie Schaffler
It's known that the peripheral nervous system, particularly neurons in the skin, sense touch and send a signal to the spinal cord and brain for processing — but it's unclear where and how the "positive" aspect of social touch in particular is registered in this chain. Using a mouse model, scientists at the University of Pennsylvania isolated a small group of touch neurons (those that express the gene Mas-related G-protein coupled receptor B4, or MrgprB4) that when activated cause a rewarding sensation. To mimic social isolation or neglect, they eliminated these touch neurons at a young age and subsequently exposed the subjects to stress in adulthood. The researchers observed increased helplessness (i.e., depression-like) behavior including decreased self-care behavior in subjects with eliminated touch neurons.
Melanie Schaffler, PhD candidate and presenting author, said that activating peripheral neurons might eventually be an effective alternative treatment for conditions like depression. "Maybe it's time to start looking elsewhere: a drug that would target the peripheral nervous system would be especially beneficial in cases where social touch isn't really an option," she said. "What we have now is evidence that it is possible to manipulate touch neurons in the skin of mammals without physically touching them. This could change behavior and stress hormone levels."
Genetic Susceptibility and Response to Stress in Adolescence
Stress can lead to mental health issues, but particularly when the stress occurs in adolescence. What role do genes play in this process? Scientists at the Feinberg School of Medicine, Northwestern University, hypothesized that adolescent rats displaying passiveness and a tendency towards anxiety because of a genetic vulnerability would react to early stress with exaggerated effects as adults.
Eva E. Redei
The researchers used a mild stressor, a swim test, on the model in adolescence and then tested stress response in adulthood. Surprisingly, they found that even in genetically vulnerable models, this limited stress experience led to better stress coping in adulthood — in other words, that the genetic predisposition was less important than the small stressor they experienced — but that it was sex-dependent. Males showed increased object and spatial memory as well as active coping, whereas females showed a decrease of fear memory and passive coping.
Eva E. Redei, professor of psychiatry and presenting author, explained that their results indicate the amount of stress played a larger role than the genetic makeup of the model. "Since resilience is defined as a response to a challenge, no resilience can be achieved without coping with a challenge… Limited acute stress during development provided that challenge that potentially can lead to resilience," she said.
Gut-Brain Vulnerabilities in Stress-Related Disorders
Most people who are exposed to trauma, including witnessing or experiencing a life-threatening event, will not experience post-traumatic stress disorder (PTSD). Yet, millions of people do go on to suffer mental illness after trauma, and the exact mechanism that makes people vulnerable to these types of stress-related disorders is not yet clear. The bacteria and microbiota in the gut have a known bidirectional communication with the brain, which can play a role in PTSD and other disorders.
Esther Sabban
Does the gut play a role in making a subject more vulnerable or resilient to traumatic stress? Scientists at New York Medical College subjected a rat model to single prolonged stress (SPS) and then subsequent isolation for two weeks; using behavioral tests, they categorized the animals as either SPS resilient or SPS susceptible. The SPS-susceptible subjects had increased amounts of urinary adrenaline and more inflammation-associated bacteria before SPS and afterwards had shorter colon length (a sign of inflammation) and higher blood-brain permeability.
Esther Sabban, the Sidney E. Frank Distinguished Professor of Psychiatry and Behavioral Sciences and presenting author, explained that identifying stress susceptibility via the gut could have many potential applications to humans. "It might be possible to develop non-invasive fecal-urinary assays to determine the vulnerability to traumatic stress… It would allow us to narrow down the number of patients needed for preventive treatments or for clinical trials with preventive strategies."
Looking Forward
Even though this research is promising, more questions remain, including: how does the severity of a stressor particularly relate to resilience? Are particular behaviors correlated to particular stressors? How does training for resilience help?
Farah explained that, though there is promising resilience research in human subjects, this kind of animal research remains critical. "Sex differences that have been noted in resilience in humans might not be sex differences per se in any biological sense. They might be differences in the ways in which society has different kinds of expectations of men and women… to try to nail down these vital questions for understanding the mechanisms of resilience, we turn to animal research."
