Why some people become addicted and others don’t

The opioid epidemic remains lethal, with nearly 100,000 Americans dying from opioid overdoses in the last year. 

Only about 10% of people who take opioids become addicted, and some of them struggle more than others to quit. Why some people become addicted and others don’t, and why some can quit and others cannot, is a major focus of addiction research. 

“Some factors underlying differences in vulnerability to opioid addiction could be related to genes or the way that genes are regulated across people. My lab is working to identify genetic predictors of vulnerability,” said neuroscientist Jonathan Gewirtz, who recently joined Arizona State University as a professor in the Department of Psychology.  

The Gewirtz lab is part of a nationwide translational research group studying the role genes play in opioid addiction. The Genetics and Epigenetics Cross-Cutting Research Team is sponsored by the National Institute on Drug Abuse and includes labs that use animal models and labs that study people.

The search for genetic markers of vulnerability to addiction

Genes can be thought of as instruction manuals for the body, and a recent study from the Gewirtz lab examined whether opioid addiction changes gene expression, or how the body interprets those instructions. The research team focused on the dorsomedial prefrontal cortex because drugs of addiction change both the connections among neurons and the overall function of this brain area. 

“We are screening for gene expression associated with opioid addiction vulnerability in brain areas, like the dorsomedial PFC, known to be dysregulated by addiction,” Gewirtz said.

Opioid use changed the expression of gene networks that are important for synaptic signaling — how neurons talk to each other — and for how the brain can rewire itself. 

The study also compared changes in gene expression across the female and male sex. Only 35% of genes impacted by opioid use were shared across the sexes, highlighting the importance of including both males and females in addiction research.

“These results underscore how important it is to understand how gene expression is critical to vulnerability to opioid addiction,” Gewirtz said. 

The biology of emotions

Gewirtz’s work on addiction is part of a larger goal to understand how the brain processes emotional states, and to contribute to translating findings from animal models into therapeutic targets for people. 

“I am interested in how emotional states are represented in the brain, how the brain induces them or is induced by them,” he said. 

Much of his research has focused on animal models of fear and anxiety, both of which are related to mental illness and drug addiction.