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

One in four depressed people may suffer from “circadian depression,” in which disruptions to the body’s internal clock contribute to a person’s mental illness, according to a large demographic and genetic study.¹ published today in the British Journal of Psychiatry.

The study found that people with circadian depression, characterized by sleep disturbances, lack of energy and reduced physical activity during the day, tended to have more severe symptoms that started 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 while the findings contribute to clinicians’ understanding of the possible causes of depression, they are preliminary and additional evidence is needed before circadian depression can be formally recognized as a disorder or treatment guidelines changed.

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

Previous studies have linked a disrupted circadian rhythm to depression². The internal 24-hour clock, controlled in the brain, regulates the sleep-wake cycle, hormones and digestion. A disrupted body clock can cause jet lag, weight gain, and lack of concentration and sleep. The latest study sought to establish circadian depression as a subtype and identify the main symptoms.

The study took the field “even further” by 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. “This is a very 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 a quarter, or 2,604 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 a preference for staying up late. Seasonality (when changes in light and day length affect mood), sleep delay, and social jet lag (a mismatch between a person’s biological clock and their social schedule) have also been proposed as criteria. Researchers determined that experiencing at least three of these would classify a person as suffering from 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 this could mean people with circadian depression are more likely to have their depression symptoms triggered by disruptions to their circadian rhythm or changes to the sleep-wake cycle, such as after daylight saving time or having a child.

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

Tonini says the team hopes that identifying whether a person’s circadian rhythm contributes to their depression will help clinicians suggest treatments that are more likely to work. It’s common for people to try multiple antidepressants before their symptoms are effectively treated – and up to 68% of people see no improvement in their symptoms after receiving standard antidepressants.³.