NEUROSCIENCE

Every day we face a myriad of stresses that can challenge our mental health—everything from our electronic devices bombarding us with information to global issues such as pandemics, mass shootings, war and climate change.

Our brains allow us to experience, interpret, interact with and change the world around us. And our brains manage to cope amazingly well with the many stresses and challenges we experience every day—most of the time.

But eventually, age and relentless overload exceed the brain’s ability to cope. What determines the tipping point between coping and crisis? And how can we prevent or treat mental health crises?

According to the World Health Organization, the three biggest influences on a person’s health are diet, exercise and social interaction.

We know a lot about the first two. Now, according to Salk researchers, it’s time to shine a light on the third. While social isolation has been linked to increased mood disorders, shortened life spans and worsened cancer and heart disease outcomes, we don’t know how.

COVID-19 quarantines highlighted the importance of social interaction. As people stayed home more often and isolated when sick, they clearly suffered in many ways. In one example of neuroscience research at Salk, scientists are now addressing a number of critical questions about the role social interaction and isolation play in our mental and physical health. Answers to these questions may ultimately pave the way for new ways to prevent or treat anxiety, depression, aggression and other mental health conditions.

Some causes of social isolation may be extrinsic—imposed upon us by a pandemic, say—but some are intrinsic, or self-imposed. For example, anxiety and autism spectrum disorders can be intrinsically isolating conditions. In contrast, children with a rare genetic condition known as Williams syndrome tend to be hyper-social—overly friendly and trusting, even with strangers.

Professor Rusty Gage and the late Professor Emerita Ursula Bellugi long studied autism spectrum disorders and Williams syndrome as two sides of the same coin. They used leading-edge stem cell technologies to re-create the conditions in the laboratory—essentially generating “mini-brains” in a dish that preserved each patient’s unique genetic background. This approach helped them connect specific genetic variations with visible changes in brain structure. By studying neurodivergent cases such as these, Salk scientists are providing new insights into the human social brain and the genetic changes that may predispose a person to social interaction or isolation.

Professor Kay Tye and collaborators have found that isolation impacts some of the same brain regions affected by hunger. In other words, while isolated, we may crave social interaction the way we crave food when we’re hungry.

Now Tye is using some of the world’s most advanced research tools to better understand the role social isolation plays in mental health. She is collecting a parts list and a wiring diagram to build a predictive model that details the brain circuitries that might explain, for example, why short-term isolation tends to end with pro-social behaviors, whereas long-term isolation more often results in withdrawal and anti-social behaviors.

Associate Professor Kenta Asahina studies genes and neurons that reduce anti-social behaviors, such as aggression, that often increase after social isolation. His group found that when fruit flies lose proteins that regulate gene expression in a small number of neurons, they act as though they were socially isolated even after they are allowed to interact with other flies. One possibility is that these proteins are necessary for restoring normal, pro-social behavioral patterns when an animal transitions from social isolation to a socially connected environment.

Flies are much simpler than humans, of course, but they are useful tools for unraveling molecular pathways involved in health and disease. Once researchers know which genes are involved in outcomes such as social isolation-related conditions, they can study those genetic counterparts in humans.

The sense of touch is a constant source of input from our environment, and it can have a large influence on how we interact with the world around us. When we’re startled by something we touch or feel, it may be a survival instinct, or it may be due to an internal state of fear or anxiety.

When rodents are socially isolated, their feelings of fear and anxiety are heightened, which can in turn change how the animals react to touch. Associate Professor Eiman Azim and his team are now identifying the parts of the brain that trigger this negative response, and they are exploring how manipulating those circuits might alleviate isolation-related stress and touch response.