An epidemic of despair is disproportionately claiming the lives of rural white Americans in the prime of adulthood. And for a second year in a row, their deaths by drugs, drink and self-destruction have caused life expectancy in the United States to fall.

That milestone, suggests an editorial in a respected medical journal, marks a sustained reversal of close to a century of improving health for Americans. And it raises a puzzling mystery: What is causing the despair, and what will restore hope and health to these battered Americans?

The opioid epidemic, which claimed the lives of 64,000 Americans in 2015 alone, “is the tip of an iceberg,” a pair of public health scholars wrote in the journal BMJ.

In an even larger public health crisis unfolding in the United States, death rates from alcohol abuse and suicides have also seen sharp increases in recent years, wrote Steven Woolf of Virginia Commonwealth University and Laudan Aron of the Washington-based Urban Institute.

Between 1999 and 2014, the suicide rate rose by 24 percent. And mounting evidence has shown that deaths linked to alcohol abuse are rising as well among white Americans.

Nowhere are these trends more dramatic than in rural counties, where decades of social and economic changes have made the lives of white Americans less secure than their parents’, write Woolf and Aron.

About 15 percent of the nation’s population — some 46 million persons — lived in counties outside metropolitan areas in 2014. In a January 2017 analysis, the Centers for Disease Control and Prevention reported that those living in nonmetropolitan areas are more likely to smoke cigarettes, to be physically inactive and obese and to suffer from high blood pressure than are metropolitan county-dwellers.

Fully 18.1 percent of rural Americans lived in poverty, compared with 15.1 percent of those living in and around cities. And people in rural counties reported less access to health care and a lower quality of health care than do those in metropolitan counties.

In October, a study published in the American Journal of Public Health found that, while premature deaths were down among all American adults between 1999 and 2015, nine of 48 subgroups studied saw increases in early mortality.

The lives of non-Latino whites, largely in rural or small or medium metropolitan counties, were mostly being shortened by suicide, drug overdoses and liver disease — a condition closely linked to alcoholism.

That study’s data showed steep declines in deaths due to HIV infection, cardiovascular disease and motor vehicle crashes among African-Americans and Latinos and in urban and suburban areas.

But those declines were more modest or nonexistent among whites living in any setting. And they were offset by dramatic increases in drug overdoses and suicides in whites, no matter where their victims lived.

The authors of the BMJ essay note that the roughly 15-year run-up in drug deaths and suicides has not been seen in black Americans.

Woolf says it’s also possible that black Americans have some “resilience factor” that white Americans do not. Perhaps, he said, African-Americans’ response to the discrimination, structural disadvantages and health inequities they’ve long endured has buffered them from following whites down their path of self-destruction.

At the same time, the despair of whites is “unclear, complex, and not explained by opioids alone,” Woolf and Aron wrote. In once-thriving communities outside the nation’s metropolitan areas, industries have collapsed.

As steel mills and coal mines have closed, timber production has gone bust, and automation has left rural communities behind, their economies and their residents’ health have suffered.