Australian researchers have identified a new subtype of depression – termed “circadian depression” – linked to disruptions in the body’s internal clock, which they believe is less responsive to traditional antidepressant treatments.
In a study published in British Journal of Psychiatry, involving clinical and genetic data from 11,380 Australians with mostly severe and recurrent depression, researchers identified circadian depression as affecting nearly a quarter (23%) of participants.
They suggest people affected by the subtype may benefit from treatments that target the body’s circadian rhythms, such as melatonin and light therapy.
While a link between mood disorders and disrupted daily rhythms has been known for some time, the researchers say the “study strengthens the evidence base for a circadian subtype of depression as a biologically valid and clinically useful phenotype of depression”.
The study’s first author, Dr Emiliana Tonini of the University of Sydney’s Brain and Mind Centre, said the researchers defined circadian depression as being in participants who showed at least three out of six features: experiencing a seasonal pattern of illness, delayed sleep timing, sleeping longer when depressed, being a night owl, waking feeling very tired, and social jetlag – when “their sleep when they go to bed during the week or when they work is very different from the weekend or when they are free to organise their day”.
“Individuals with circadian depression have more severe mental health symptoms,” Tonini said during a press briefing. “The age of onset of their depression was younger compared to those with non-circadian depression, but they also had more episodes and also more complex trajectories, more suicidality, more hypomanic and psychotic-like symptoms as well.”
The researchers also found that those with circadian depression had higher genetic risk for ADHD and mood disorders, “but also a series of metabolic and inflammatory markers”, Tonini said. “This is important because that indicates that circadian depression is not just depression with bad sleep, but actually there is an underlying biology that is quite distinct from other forms of depression.”
The researchers hope that being able to clinically diagnose circadian depression in future may help with more tailored treatments, particularly for young people seeking mental health support for the first time.
Prof Ian Hickie, a psychiatrist and co-director of the Brain and Mind Centre, said: “What is critical about being in this circadian type is its poor response to the standard therapies, those which are typically recommended in the guidelines.”
SSRIs and SNRIs, typical first-line antidepressant drugs, were less effective and had more side effects for people with the circadian subtype, the study found.
For those with circadian depression, “chronobiological treatments – things focused on the sleep-wake cycle, particularly … to do with morning light exposure, daylight activity, regularity of sleep-wake cycles, regularity of food schedules, is critical”, Hickie said.
In their study, the researchers noted that the participants were “were limited to those of genetically inferred European ancestry, which may limit generalisability”, and that “future studies are needed to replicate our findings in diverse samples”.
The director of the Monash Alfred Psychiatry Research Centre, Prof Jayashri Kulkarni, who was not involved in the research, described it as a “really well-conducted study”.
“They have got a polygenic risk score, which means that they’ve actually managed to tie certain types of depression to a specific genetic profile,” she said. “That will be important for onward treatment.”
The research did not take into account the hormonal impacts of menopause, Kulkarni added, “which is predominantly one of the things that women describe as causing sleep disturbance … That would be another factor that might be worth considering.”
Prof Andrew Coogan, a behavioural neuroscientist at Maynooth University in Ireland, said: “We have known for a long time that major depression is linked to changes in the body clock that make people later to bed and later to rise so the findings are not overly surprising.”
He cited a “lack of detail as to how the cluster of features of, and the criteria for, the proposed circadian subtype of depression was arrived at”.
“The results of this exploratory study are best interpreted as initial if interesting findings that warrant further examination,” he said.
