One in Four People With Depression May Have Circadian Depression Linked to Body Clock Disruption, Study Finds

About one in four people with depression may have a form of the illness driven in part by disruptions to the body's internal clock, according to a large new study that researchers say could eventually help doctors choose more effective treatments.

The study, published in the British Journal of Psychiatry, describes what its authors call "circadian depression," a subtype marked by disrupted sleep, low energy and reduced physical activity during the day. People who fit the profile tended to have more severe symptoms, developed depression at a younger age and were less likely to respond to standard antidepressants.

Experts not involved in the research said the findings are an important step toward understanding the biology of depression, but cautioned that they are preliminary. More evidence is needed, they said, before circadian depression can be formally recognized as a distinct disorder or before treatment guidelines change.

What the researchers found

The research team, which included circadian researchers Emiliana Tonini and Jacob Crouse of the University of Sydney, analyzed data from 11,380 people of European ancestry with severe depression.

Participants were assessed against six proposed criteria linked to disruption of the body's internal clock: excessive daytime sleepiness, morning tiredness, a preference for staying up late, seasonal patterns in mood, delayed sleep and "social jet lag," the mismatch between a person's natural sleep timing and the schedule imposed by work or social obligations.

People who met at least three of the six criteria were classified as having circadian depression. Nearly a quarter of participants, 2,604 people, met that threshold.

Compared with people with other forms of depression, those with the circadian subtype had more severe symptoms and an earlier age of onset. They were also more likely to be female and less likely to improve on conventional antidepressants.

Genetic and biological clues

The study also examined genetic and biological markers, offering clues about what may set circadian depression apart.

People with the circadian subtype had higher genetic risk for attention-deficit/hyperactivity disorder and for other mood disorders, including anxiety and major depressive disorder. They also showed signs of an increased risk of inflammation and disrupted metabolism.

Those findings suggest the condition may involve a distinct mix of biological processes, rather than simply being depression accompanied by poor sleep.

Why it matters for treatment

Depression is among the most common mental health conditions worldwide and a leading cause of disability. Yet many patients do not get better with the first treatments they try.

A 2021 review cited by the researchers found that up to 68% of people do not improve with standard antidepressants. Patients often cycle through several medications over months before finding one that works, if they find one at all.

Tonini said the team hopes that identifying when the body clock is involved will help clinicians select treatments that are more likely to work for individual patients.

That could eventually include therapies aimed directly at the body's internal clock, although the study itself did not test specific treatments.

Outside experts see promise

Colleen Loo, a clinical psychiatrist and researcher at the University of New South Wales in Sydney who was not involved in the study, said the research takes the field "one step further" toward uncovering the biological mechanisms behind depression.

"It's a really useful contribution to the science of understanding depression," Loo said.

How the body clock works

The circadian rhythm is the roughly 24-hour internal cycle that regulates sleep and wakefulness, hormone release, body temperature, appetite and many other functions. It is governed by a master clock in the brain that responds largely to light and darkness.

When that rhythm falls out of sync with a person's daily life, through shift work, irregular sleep, late-night screen use or seasonal changes in daylight, it can affect mood, energy and concentration.

Scientists have long observed links between sleep problems and depression. Insomnia and oversleeping are both common symptoms of the illness, and people with sleep disorders face a higher risk of developing depression. Seasonal affective disorder, in which depression recurs during the darker months of the year, is one well-known example of how changes in light exposure can affect mood.

The new study builds on that work by attempting to define a specific group of patients for whom circadian disruption may be a central feature of their illness rather than a side effect.

Caution urged

Researchers in the field stressed that the findings do not yet change how depression should be diagnosed or treated.

The criteria used to define circadian depression are still being proposed and tested, and the study was limited to people of European ancestry with severe depression. It is not yet clear whether the findings apply to people with milder illness or from other backgrounds.

Because much of the analysis relied on associations, the study also cannot show whether disruptions to the body clock cause depression, result from it or both.

Experts said further research, including clinical trials, will be needed to determine whether treating circadian disruption improves outcomes for this group of patients.

Practical steps

Health experts generally advise that people experiencing symptoms of depression speak with a doctor or mental health professional rather than attempt to self-diagnose.

Habits that support a stable body clock, such as keeping regular sleep and wake times, getting daylight exposure in the morning and limiting bright screens late at night, are widely recommended for overall health. But they are not a substitute for professional care for people with depression.

For now, researchers say the concept of circadian depression offers a promising new way of thinking about a complex illness, one that may eventually lead to more personalized care for the millions of people who live with it.