Body clock disruptions contribute to one in four cases of depression, suggests large study

One in four people with depression could have ‘circadian depression’, in which disruptions to the body’s internal clock contribute to a person’s mental illness, according to a large population and genetics study¹ published today in the British Journal of Psychiatry.

The study found that people with circadian depression, which is characterized by disrupted sleep, low energy and reduced physical activity during the day, tended to have more severe symptoms that start at a younger age than those with other forms of depression. They also tended to be female and less likely to respond to conventional antidepressants.

Researchers in the field say that although the findings add to clinicians understanding of the possible causes of depression, they are preliminary and more evidence is needed before circadian depression can be formally recognized as a disorder or treatment guidelines are changed.

Major depressive disorder is the second most common mental-health disorder globally, but its severity and response to treatment can vary substantially between individuals. Although research has sought the underlying mechanisms to explain these differences, this has had a limited impact on prognosis and treatment so far, say the authors.

Previous studies have linked a disrupted circadian rhythm to depression. The 24-hour internal clock, which is controlled in the brain, regulates the sleep–wake cycle, hormones and digestion. A disrupted body clock can make people feel jet-lagged, gain weight, and have poor concentration and sleep. The latest study sought to establish circadian depression as a subtype and identify key symptoms.

The study has taken the field “one step further” to uncovering the underlying biological mechanisms in some people with depression, says Colleen Loo, a clinical psychiatrist and researcher at the University of New South Wales in Sydney, Australia. “It’s a really useful contribution to the science of understanding depression,” she says.

One in four

The study of 11,380 people of European ancestry with severe depression found that nearly one-quarter — 2604 people — met at least three of the study’s six proposed criteria for circadian depression. These include excessive daytime sleepiness, feeling tired in the morning and preferring to stay up late. Seasonality (when changes in light and the length of the day affect mood), delayed sleep and social jet lag (a mismatch between a person’s biological clock and their social schedule) were also proposed criteria. The researchers determined that meeting at least three would classify a person as having this type of depression.

The team found that circadian depression was associated with higher genetic risk factors for attention deficit hyperactivity disorder and other mood disorders, such as anxiety and major depressive disorder. Co-author Emiliana Tonini, a circadian researcher at the University of Sydney, says that this could mean that people with circadian depression are more likely to have their depression symptoms triggered by disruptions to their circadian rhythm or sleep–wake cycle changes, such as after daylight saving time or having a child.

They also found that circadian depression was linked to an increased risk of inflammation and disrupted metabolism. Co-author Jacob Crouse, also a circadian researcher at the University of Sydney, says that the findings suggest that metabolic dysfunction could affect a person’s mood, energy levels and sleep.

Tonini says that the team hopes that identifying whether a person’s circadian rhythm is contributing to their depression will help clinicians to suggest treatments that are more likely to work. It is common for people to try multiple antidepressants before their symptoms are effectively treated — and up to 68% of people do not see an improvement in symptoms after receiving standard antidepressants².