Researchers Propose 'Circadian Depression' as a Distinct Body-Clock Subtype

Australian researchers say a distinct form of depression tied to the body's internal clock may affect roughly one in four people with severe or recurrent illness, and that it may respond poorly to standard antidepressants. The proposed subtype, called "circadian depression," was described in a study published Oct. 21 in The British Journal of Psychiatry.

The team suggests that treatments aimed at the sleep-wake cycle, such as melatonin and bright light therapy, could help these patients. Outside experts told the outlets covering the work that the idea is promising but still needs more testing before it changes clinical practice.

How the researchers defined the subtype

The team, based at the University of Sydney, analyzed data from 11,380 adults ages 18 to 90 in the Australian Genetics of Depression Study, according to Live Science. The study looks at how genes and life experiences shape depression and the response to treatment. The Guardian reported that most participants had severe and recurrent depression.

Participants counted as having the circadian subtype if they showed at least three of six features: a seasonal pattern to their mood, late sleep timing, sleeping longer when depressed, night-owl habits, waking up very tired, and social jet lag. Social jet lag is a mismatch between sleep schedules on workdays and on free days.

By that definition, 2,604 people fit the subtype, according to Live Science. The Guardian put the share at 23% of participants, and ScienceAlert described it as about 1 in 4. The concept was first set out in 2021, Live Science reported.

What set the group apart

Compared with other participants, the circadian group was younger and developed depression earlier, at around 19 versus about 23, Live Science reported. The group skewed female. Dr. Emiliana Tonini, the study's first author, said at a press briefing, as quoted by the Guardian, that these participants had more severe symptoms, more episodes, more complex trajectories, and more suicidality, along with more hypomanic and psychotic-like symptoms.

The team also calculated polygenic risk scores, which add up the effects of many small genetic variants. According to Live Science, the circadian group had a higher genetic risk for depression, anxiety, ADHD and bipolar disorder. They also had a higher genetic risk for higher body weight, insulin resistance, inflammation, insomnia and late sleep habits. Tonini said the findings show the condition is "not just depression with bad sleep," pointing to an underlying biology distinct from other forms.

ScienceAlert reported some overlap with atypical depression, but about 1,400 cases met the criteria for atypical depression without the circadian subtype. The researchers read that as a sign the two may be separate.

Why it matters for people with depression

The study found that people in the circadian group reported less benefit from SSRIs and SNRIs, the usual first-line antidepressants, and more side effects, including drowsiness, nausea, anxiety and weight gain. Dr. Ian Hickie, co-director of the University of Sydney's Brain and Mind Centre, told reporters that a poor response to guideline-recommended therapies is the critical feature of this type.

For these patients, Hickie said, treatments built around the body clock are important. He named morning light exposure, daytime activity, and regular sleep and meal schedules. Jacob Crouse, a researcher on the team, said clinicians should consider light therapy and melatonin much earlier for people with this presentation, according to ScienceAlert. Crouse also said that people for whom antidepressants are not working should talk to their clinician about their individual circumstances.

The researchers hope that a formal diagnosis would eventually allow more tailored care, particularly for young people seeking help for the first time, the Guardian reported.

Why experts urge caution

The subtype is a proposal, not an established diagnosis. Brant Hasler, a sleep researcher at the University of Pittsburgh who was not involved, noted that the study relied on participants' own reports of their sleep. Such reports correlate only modestly with direct measures of circadian timing, such as melatonin in saliva, he told Live Science. Someone can see themselves as an evening person and still have a body clock that is not physiologically delayed, he said.

Dr. Ruth Benca of Wake Forest University School of Medicine, also not involved, said that if circadian disruption is a core mechanism, treatments that ignore it may be less effective. She added that it may not be the only reason. People with more pronounced circadian disturbances often have more severe illness and other psychiatric conditions, which can contribute to treatment resistance, she said.

Andrew Coogan, a behavioral neuroscientist at Maynooth University in Ireland, said the link between depression and a shifted body clock has been known for a long time, so the findings are not especially surprising. He cited a lack of detail on how the six features and criteria were chosen, and called the results "initial if interesting findings."

Jayashri Kulkarni of the Monash Alfred Psychiatry Research Centre, also not involved, called it a well-conducted study and said linking depression types to a genetic profile could matter for future treatment. She noted that it did not account for the hormonal effects of menopause, which many women describe as a cause of sleep disturbance.

The authors acknowledged that participants were limited to those of genetically inferred European ancestry, which may limit how far the results apply. They said future studies should replicate the findings in more diverse samples.

Sources: Live Science, The Guardian, ScienceAlert