Their problem may not simply be how much they sleep or how poorly, but when their internal clock tells them to.
In an analysis of 11,380 Australians with a history of depression, researchers identified 2,604 people, or 23 percent, whose sleep habits and symptoms fit a proposed new subtype of depression called circadian depression.
Someone whose internal clock runs late may feel wide awake at midnight but exhausted at 8 a.m.
Within this proposed subset, depression had begun at an average age of 18.7 in the circadian group, versus 23.2 among the others.
Some independent experts outside the study question whether the so-called circadian depression group is biologically distinct.
Credit: ZME Science.
For some people with depression, every day feels like waking up with jet lag but without the flight. They sleep longer, wake exhausted, and find themselves most alert when the rest of the world is winding down. Their problem may not simply be how much they sleep or how poorly, but when their internal clock tells them to.
In an analysis of 11,380 Australians with a history of depression, researchers identified 2,604 people, or 23 percent, whose sleep habits and symptoms fit a proposed new subtype of depression called circadian depression. The patients developed depression younger, experienced more severe symptoms, and found common antidepressants less helpful.
In other words, a large portion of the population may experience depression due to their body’s internal clock, which perhaps is not in sync with the tune of modern life, rather than due to anxiety.
Our internal timekeeping systems, or circadian clocks, respond to light and help regulate sleep, appetite, alertness and mood.
“When it’s off, you feel jet-lagged all the time,” Ian Hickie, a University of Sydney psychiatrist and senior author of the study, told ScienceAlert.
Why look at the body clock?
Depression can look strikingly different from one patient to another. Some cannot sleep; others sleep excessively. Some lose their appetite; others gain weight. Yet psychiatrists often begin treatment with similar medications, sometimes trying several before finding one that helps.
Only about 30% of patients experience full relief from their very first antidepressant medication. Around one-third of people do not respond to standard antidepressant drugs overall.
Researchers at the University of Sydney wanted to investigate whether a subset of patients might share a particular vulnerability owed to disruption of their internal clocks.
The investigation goes well beyond poor sleep making people miserable. Someone whose internal clock runs late may feel wide awake at midnight but exhausted at 8 a.m. When school or work demands an earlier schedule, the mismatch can resemble living in a different time zone without ever traveling.
To investigate, the team examined questionnaires and genetic data from the Australian Genetics of Depression Study. The 11,380 participants predominantly had severe or recurring depression.
Researchers looked for six clues: a strong preference for evenings, unusually late sleep timing, sleeping more than usual during depression, feeling very tired on waking, seasonal changes in mood and behavior, and social jet lag.
The latter refers to the discrepancy between biological time, determined by our internal body clock, and social times, mainly dictated by social obligations such as school or work. Someone might force themselves awake at 7 a.m. during the week but naturally sleep until 11 a.m. on weekends.
Participants who met at least three of the six criteria entered the circadian group. The most common combination involved excessive sleep during depression, pronounced morning exhaustion and an evening preference.
What made these patients different?
Within this proposed subset, depression had begun at an average age of 18.7 in the circadian group, versus 23.2 among the others.
More than half reported at least ten depressive episodes, compared with just over a third of other patients with more typical depression. They also reported greater psychological distress, more suicidal thinking and more experiences resembling mania or psychosis.
This may be mostly related to genes. Participants in the circadian group had somewhat higher inherited risk scores for ADHD, bipolar disorder and depression, alongside traits associated with inflammation and insulin resistance.
Some symptoms overlapped with atypical depression, a recognized subset that can involve excessive sleeping and weight gain. But more than 1,400 participants with atypical depression did not meet the circadian criteria.
That suggests the two groups are not interchangeable, despite the overlap sometimes.
A new target for treatment?
People in the circadian group rated two common antidepressant classes, SSRIs and SNRIs, as somewhat less effective and reported more side effects.
Previously, research linked evening chronotypes to poorer antidepressant responses. Separately, clinical trials have suggested that bright-light therapy can help some people with depression. Another review of 58 studies found evidence linking improvements in mood to better circadian alignment, particularly among people with delayed internal clocks.
Co-author Jacob Crouse argues that clock-focused treatments, including light therapy and melatonin, deserve consideration earlier in care.
“Because circadian depression is linked to people’s internal body clock, treatments targeting the circadian rhythm, such as light therapy and melatonin, may be much more relevant, and clinicians should reach for these much earlier in people with this presentation,” he said. But no trial has yet shown that people selected by these six criteria benefit more from such treatments
For now, circadian depression remains a promising proposal rather than an established diagnosis. Its practical message is simpler: when depression persists despite treatment, the timing of someone’s sleep may deserve as much attention as its duration.
Some independent experts outside the study question whether the so-called circadian depression group is biologically distinct. Finding genetic markers for late sleeping, for instance, is less surprising when late sleeping helped define the group.
“That means these genetic associations do not independently establish a distinct biological subtype of depression,” Ronan Lordan of the Royal College of Surgeons in Ireland told the Science Media Centre.
The practical lesson is not to replace antidepressants with melatonin or a light box. It is to take sleep timing seriously when assessing depression, particularly when treatment fails, and to discuss possible interventions with a clinician.
The findings were reported in The British Journal of Psychiatry.
