SC Connecticut News

A recent Yale study indicates that physical frailty may increase the risk of developing depression and could be a potential target for intervention. The research, published on May 23 in Nature Communications, highlights the need for routine assessment of physical frailty in clinical practice.

Physical frailty is identified by five indicators: weight loss, exhaustion, feelings of weakness, physical inactivity, and slow walking speed. This condition also raises the risk of bone fractures, hospitalization, lower quality of life, and premature death. Previous studies have suggested a link between physical frailty and declining mental health.

To explore this relationship further, Yale researchers utilized data from the UK Biobank, which includes health information from over 500,000 adults in the United Kingdom. They analyzed data from more than 350,000 individuals aged 37 to 73 who had undergone initial assessments between 2006 and 2010 and a follow-up approximately 12 years later.

Participants were categorized as non-frail (none of the five indicators), pre-frail (one or two indicators), or frail (three or more indicators). Researchers then examined how many participants were diagnosed with depression during their follow-up assessments.

The findings revealed that compared to non-frail individuals, those classified as pre-frail or frail were 1.6- and 3.2 times more likely to be diagnosed with depression after their first assessment. The likelihood of depression increased with greater severity of frailty.

"We also found this association was stronger in males and in middle-aged individuals — people younger than 65 — than it was for females or older individuals," said Rongtao Jiang, lead author of the study and a postdoctoral associate at Yale School of Medicine’s Department of Radiology and Biomedical Imaging.

The study also investigated factors contributing to the link between frailty and depression through "mediation analyses." This statistical approach examines whether a third factor influences the relationship between two factors—in this case, frailty and depression.

Researchers discovered that certain inflammatory markers—such as neutrophils and leukocytes (white blood cells) and C-reactive protein produced by the liver—mediated the relationship between frailty and depression. Additionally, reduced volume in five brain regions played a mediating role.

"This tells us that maybe the association between frailty and depression can occur through the regulation of inflammatory markers or brain volume," said Jiang. It is possible that frailty leads to inflammation in the brain and changes in brain structure, which subsequently result in depression. More research is needed to clarify this progression; however, these findings provide strong evidence connecting frailty with depression.

"Frailty may be a very important risk factor for the development of depression," Jiang noted. "Depression affects millions globally but lacks effective treatments or prevention strategies. This significant association suggests that modifying someone's frailty status might have important implications for preventing depression."

Incorporating routine assessments for physical frailty into healthcare visits could potentially reduce depression incidence by preventing or delaying its onset. "Assessing frailty is a relatively inexpensive and easy procedure," said Dustin Scheinost, associate professor of radiology and biomedical imaging at Yale School of Medicine and senior author of the study. "More research is needed, but it’s possible frailty might be a target for intervention."