South SFV Today

In a world where adversity seems omnipresent, some individuals exhibit an uncanny ability to withstand even the most traumatic experiences without suffering lasting damage to their mental health. This trait, known as psychological resilience, is the subject of study for psychiatrist Victor Carrión, MD, the John A. Turner, MD, Endowed Professor for Child and Adolescent Psychiatry.

Carrión's research focuses on understanding how personality, social and family connections, physical health and genetics interact to shape resilience. "Over the past decades, I and others have done research to elucidate the impact of stress on brain structure and function," Carrión said. "One potential mechanism is the neurotoxic effects of the stress hormone cortisol. But we still don’t know much about the biological basis of resilience.”

To delve deeper into this question, Carrión has partnered with Alexander Urban, PhD, an associate professor of psychiatry and behavioral sciences and of genetics. They are using neural organoids — miniature cellular structures that mimic the human brain — to explore the molecular underpinnings of resilience.

The researchers are combining laboratory studies with a population study in Puerto Rico where students have experienced multiple natural disasters over the past decade. These traumatic events have left many students grappling with anxiety, depression and post-traumatic stress disorder.

Neural organoids provide a valuable tool for these studies because they can be grown from easily obtained skin or blood cells. This means they share the DNA sequences of the person from whom they are derived. Therefore any genetic variations that might affect mental health will be reflected in how cells in the organoid communicate and organize themselves.

Urban and his team are leveraging high-throughput sequencing technology to examine not only DNA sequences but also gene activity and epigenetic tags which influence gene expression in response to environmental cues.

This approach has been made possible by advancements in neural organoid technology developed by Sergiu Pasca, MD, Kenneth T. Norris, Jr. Professor II of Psychiatry and Behavioral Sciences. "I wanted to push the boundaries and make the human brain accessible so that we can transform psychiatry through molecular biology," Pasca said.

Urban and Carrión are now using these organoids to identify key genes involved in resilience and mental health, as well as environmentally influenced epigenetic tags that modulate those genes’ activity.

“Cortisol exposure allows us to model the effects of stress on these cells,” Carrión said. “What innate characteristics in a person’s brain confer resilience, and are there ways to intervene to help people struggling with post-traumatic stress or anxiety? The cortisol model allows us to study genes that are activated or deactivated when the cells are ‘stressed.’”

The researchers hope their work will lead to new interventions that can help individuals become more resilient. “Resilience and non-resilience aren’t binary states,” Carrión said. “They exist along a continuum of possible responses to environmental stress and trauma."

Ultimately, this research could go beyond understanding resilience and shed light on other conditions including schizophrenia or autism. "Most of us know about genes and our environment," Carrión concluded. "Finally, we are beginning to understand how stress directly impacts our genetic code and whether we can intervene to help people be more resilient.”