Sydney study proposes 'circadian' depression subtype with poorer response to common antidepressants

Researchers from the University of Sydney's Brain and Mind Centre have published a study in the British Journal of Psychiatry. It describes a proposed subtype of depression that they call "circadian depression" and link to disruption of the body's internal clock.

The study used clinical and genetic data from more than 10,000 Australians with depression. The Guardian gives the figure as 11,380 and says most had severe and recurrent depression. Medical Xpress describes participants as having severe, recurrent or persistent depression. According to Medical Xpress, the data came from the nationwide Australian Genetics of Depression Study.

The researchers classified nearly a quarter of participants as having the circadian subtype. The Guardian reports 23%. Medical Xpress reports nearly 25%, or 2,604 people.

According to the study, SSRIs and SNRIs, typical first-line antidepressants, were less effective and had more side effects in this group. These participants also had a younger age of onset and more severe symptoms, including more suicidality. They had higher genetic risk for ADHD and for inflammatory-related markers or health problems.

Features linked to the subtype include a seasonal pattern of illness, sleeping longer when depressed, waking very tired and being a night owl. According to The Guardian, participants were classified with the subtype if they showed at least three of six features, which also included delayed sleep timing and social jetlag.

According to The Guardian, the study notes it was limited to people of genetically inferred European ancestry and that replication in diverse samples is needed.

What is disputed

The reports differ on treatment. Medical Xpress states that the subtype is more responsive to body-clock therapies such as melatonin, melatonin-targeted antidepressants and light therapy. The Guardian reports only that the researchers suggest such treatments may help. The reports reviewed by Vocemundi do not describe any trial of circadian treatments in this group.

What each side says

The Guardian quoted first author Dr Emiliana Tonini as saying the subtype "is not just depression with bad sleep, but actually there is an underlying biology that is quite distinct from other forms of depression."

Prof Ian Hickie, co-director of the centre, was quoted by The Guardian as citing the subtype's "poor response to the standard therapies". Medical Xpress quoted co-senior author Dr Jacob Crouse as saying clinicians "should reach for these much earlier in people with this presentation", referring to light therapy and melatonin.

Prof Jayashri Kulkarni of the Monash Alfred Psychiatry Research Centre, who was not involved in the study, called it a "really well-conducted study", according to The Guardian. She noted it did not account for menopause-related hormonal effects on sleep. Prof Andrew Coogan of Maynooth University told The Guardian's readers, via its report, that the results are "best interpreted as initial if interesting findings that warrant further examination". He also pointed to a lack of detail on how the subtype's criteria were derived.

Analysis

If confirmed by further research, a circadian subtype could prompt clinicians to ask more about sleep timing and seasonal patterns when choosing treatment. That remains conditional. The reports reviewed by Vocemundi describe associations in a single, ancestry-limited sample, not a test of whether body-clock treatments work better. They also do not explain how treatment response was measured or how the classification threshold was chosen. Possible next steps include replication in more diverse populations and controlled trials of melatonin or light therapy in this group. Results could support, refine or weaken the proposed subtype.

Produced by the Vocemundi newsroom with AI assistance.