[5] Life expectancy in the United States declined further to 76.4 years in 2021, with the main drivers being the COVID-19 pandemic along with deaths from drug overdoses, suicides and liver disease.

[8] Emotional despair refers to feelings of sadness, irritability, loneliness and apathy and may partly impede the process of creating and nourishing interpersonal relationships.

Lastly, biological despair relates to dysfunction or dysregulation of the body's stress reactive system and/or to hormonal instability.

[7][9] Unstable mental health, depression, suicidal thoughts and addiction to drugs and alcohol affect people of every age, every ethnicity, and every demographic group in every country in the world.

[10] The AIDS epidemic in the US was brought under control; in 2018, only 37,968 people received an HIV diagnosis in the USA and its 6 dependent areas, which is an overall 7% decrease compared with the year 2014.

[12] Cardiovascular disease and cancer, the two biggest killers in middle age, are also on a decline,[9] even though the still growing problem with obesity remains uncontrolled.

Despite all of these satisfactory numbers, White non-Hispanic population exhibits an increase in premature deaths, especially in those caused by suicide, drug overdose and alcoholic liver disease.

For example, in 2015, drug, alcohol and suicide mortality was more than two times higher among US White non-Hispanics in comparison to people from the United Kingdom, Sweden or Australia.

In comparison to US Black non-Hispanics, the mortality and morbidity rates are still lower; nevertheless the gap between these groups is narrowing quickly and, for example, for people aged 30–34 the difference between these two ethnicities has almost completely diminished.

The factors that seem to exacerbate diseases of despair are not fully known, but they are generally recognized as including a worsening of economic inequality[17][18] and feeling of hopelessness about personal financial success.

[19] This increase in rates of mental distress and diseases of despair have been attributed to the flaws in contemporary capitalism and policies associated with the ideology of neoliberalism, which seeks to release markets from all restrictions and reduce or eliminate government assistance programs.

[20][21][22] The overall loss of employment in affected geographic regions, and stagnant wages and deteriorating working conditions along with the decline of labor unions and the welfare state, are widely hypothesized factors.

[9][27] They argue that the ultimate cause is the sense that life is meaningless, unsatisfying, or unfulfilling, rather than strictly the basic economic security that makes these higher order feelings more likely.

As such, other rich countries, while facing challenges associated with globalization and technological change, did not experience a "long-term stagnation of wages, nor an epidemic of deaths of despair.

"[28] Recent data show that diseases of despair pose a complex threat to modern society and that they are not correlated only to the economic strength of an individual.

Social connections, level of education, place of residence, medical condition, mental health, working opportunities, subjective perception of one's own future – all of these play a role in determining whether the individual will develop diseases of despair or not.

[31][32] Though certain health aspects like stress can be concurrent with the crisis, other biopsychosocial risk factors such as job loss, housing precarity, and food insecurity can manifest over time.

[37] Particularly in Milwaukee County, Wisconsin, it was found that the pandemic had remarkably escalated the number of monthly overdose deaths, due to opioids.

[37] In addition, it was found that the worst of these drug impacts seemed to primarily occur in poor and urban neighborhoods, especially affecting Black and Hispanic communities.

[37] After the COVID-19 pandemic hit, and following the stay-at-home order issued on March 23, 2020, the peak monthly overdose death total rose to 57, during the post-pandemic scenario.

[37] The Milwaukee County Medical Examiners' Office provided detailed death certificates of OODs, which included information on the drugs involved in the overdose.

[close paraphrasing] The urban tracts that experienced a 10,280% increment in OODs suffer from racial and economic segregation, concentrated poverty, and a lack of educational and employment opportunities.

Despite their high economic and social well-being, suburban tracts have still been affected by pandemic-related stress, which likely contributed to the increase in OODs.

[9] Starting in 1998, a rise in deaths of despair has resulted in an unexpected increase in the number of middle-aged White Americans dying (the age-specific mortality rate).

[40] The phrase diseases of despair has been criticized for medicalizing problems that are primarily social and economic, and for underplaying the role of specific drugs, such as OxyContin, in increasing deaths.