Counties where auto plants close see significant spikes in fatal opioid overdoses within five years, according to newly published research from the University of Pennsylvania, suggesting a strong association between eroding economic opportunity and premature American deaths.

Published Monday in medical journal JAMA Internal Medicine, the study from researchers at the University of Pennsylvania and the Massachusetts General Hospital found that within five years of an auto plant closing, opioid overdose deaths among working-age adults were 85% higher than in counties where plants had not closed.

More than 130 people in the United States die each day from opioid overdoses, according to estimates from the National Institute on Drug Abuse.

“Major economic events, such as plant closures, can affect a person’s view of how their life might be in the future. These changes can have a profound effect on a person’s mental well-being, and could consequently influence the risk of substance use,” said Atheendar Venkataramani, the study’s lead author and an assistant professor in the University of Pennsylvania’s Perelman School of Medicine, said in a news release. “Our findings confirm the general intuition that declining economic opportunity may have played a significant role in driving the opioid crisis.”

Researchers looked at the counties where manufacturing represented the greatest share of local employment between 1999 and 2016, largely in the Midwest and South, which are also regions with the nation’s worst mortality rates. They also studied counties in “commuting zones” which fed into these labor markets. About 5.5 million manufacturing jobs were lost between 2000 and 2017, according to the Bureau of Labor Statistics, though recent years have seen some recovery. Opioid deaths rose sixfold in the same period, according to the National Institute on Drug Abuse.

While the 112 counties studied had a similar baseline of opioid overdose deaths at the beginning of the period studied, the 29 counties impacted by plant closures saw a more drastic increase in these fatalities within just two years. Within five years, death rates jumped by 8.6 deaths per 100,000 people in a county, an 85% increase compared to counties that didn’t experience closures, the study found. The problem was starkest for white, working-age men.

Although researchers were clear that the study did not show a causal relationship between plant closures and opioid overdose fatalities, their data speaks to the correlation between declining economic and social well-being and rising death rates among America’s working class. Research from Princeton University economists Anne Case and Angus Deaton found that overall deaths from suicide, drugs and alcohol, or “deaths of despair,” have risen steeply since 2000, especially for middle-aged white Americans without college or high school educations. The rise in these deaths has contributed to a drop-off in American life expectancy, which has declined each of the past three years.

“Mortality from deaths of despair far surpasses anything seen in America since the dawn of the 20th century,” a September report from the U.S. Congress Joint Economic Committee reads. “The recent increase has primarily been driven by an unprecedented epidemic of drug overdoses.”

Still, existing literature regarding premature death and diminished economic well-being, which has often hinged on broader economic indicators such as income and unemployment, has yielded mixed results. Researchers chose to focus on auto plant closures because they often come as a surprise to workers and have an acute and protracted impact, offering a chance to examine the ramifications of evaporating economic opportunities. They also noted that auto plant closures are often treated as emblematic of the wider decline in U.S. manufacturing in the past 20 years, a trend which has explicitly been associated with the opioid crisis.

“Our results are most relevant for the worsening population health trends in the industrial Midwest and South, regions that have experienced some of the largest increases in opioid overdose deaths and in which the automotive production and other manufacturing industries have long been economically and culturally significant,” Venkataramani said in the release.

Extensive research has shown that the opioid crisis has its roots in the late 1990s, when pharmaceutical companies convinced the medical community that addiction was not a risk with opioid pain relievers, leading doctors to prescribe them at far greater rates and ultimately to a disastrous rise in opioid abuse. Although prescribing rates have been falling since the 2010, opioid overdose deaths have continued to climb, suggesting the opioid epidemic’s stranglehold on the U.S. should also be analyzed through the forces that drive people to take them, the researchers said.

“While we as clinicians recognize and take very seriously the issue of overprescribing, our study reinforces that addressing the opioid overdose crisis in a meaningful way requires concurrent and complimentary approaches to diagnosing and treating substance use disorders in regions of the countries hardest hit by structural economic change,” Venkataramani said.