Researchers identify new ‘circadian depression’ subtype

Researchers at the University of Sydney’s Brain and Mind Centre looked at data from over 15,000 people with depression and found that a large number were affected by circadian disturbances, or ‘circadian depression.’ 

First author Dr Emiliana Tonini is a postdoctoral researcher in the Youth Mental Health and Technology team.

“In this large data set of Australians with depression, we defined circadian disturbance criteria that we think are markers of the potential circadian depression subtype,” said Dr Tonini.

“Examples include having a delayed sleep midpoint, being an evening chronotype, and having irregular sleep cycle,” she said.

Participants came from the Australian Genetics of Depression Study (AGDS), a nationwide cohort study exploring genetic and psychosocial factors influencing the aetiology of depressive disorders and antidepressant response.

“We found that 23% of people met our proposed criteria for circadian depression. 

“It’s roughly what we expected, but I was also surprised that it's a large proportion. 23% is definitely not insignificant.

“And these people also reported that conventional treatment didn't work that well for them. That's a very large proportion of individuals who might not be happy with their care.”

What is circadian depression?

Circadian depression is linked to the body’s 24-hour internal clock that regulates our sleep-wake cycle. 

It is characterised by being more resistant to treatment by common serotonin-based antidepressants (ie, SSRIs) but is more responsive to behavioural and medical therapies targeting the body clock’s unique brain circuits, such as melatonin, melatonin-targeted antidepressants and light therapy.

Co-author Dr Jacob Crouse is a senior research fellow with the team. 

“Almost all life on earth evolved under a stable 24-hour light-dark cycle,” said Dr Crouse.

“That was important for survival. It evolved to regulate most of our physiology and behaviour and regulates our health and wellbeing,” he said.

“The way that we live in modern life confuses the clock. It causes trouble for our energy, mood, and metabolism.”

Dr Ian Hickie is a co-author of the study.

“Ian Hickie has been working on the concept behind circadian disturbances being linked to mood for a long time; there's been a long progress,” said Dr Crouse.

“The team proposed circadian depression as a potential subtype a few years ago, and this study is an exploration of that hypothesis.”

“We know that treatments that improve circadian function, like bright light therapy, can improve depression.”

“A lot of the approaches to depression are very generic. Depression often is seen and treated as one, uniform disorder.”

“There is trial and error in people finding the correct medication.”

“We hope that by having this narrower subtype, informed by the underlying biology, we can look at personalising treatments to individuals, which might work better.”

How GPs and specialists can engage patients

Dr Tonini says that she hopes the new research will lead to more conversations about circadian rhythms.

“Something that we hear quite often from lived experience is that people don't necessarily talk about sleep that much with their clinicians,” she said.

“Sometimes they talk about sleep hygiene, but there's not much conversation around the circadian rhythm — this 24-hour period.”

“GPs [talking about] that circadian rhythm, the body clock, might play an important role.”

Dr Crouse noted that wearable devices, and finding out about your chronotype, can be a useful tool.

Interesting alignments within the depression subtype

Dr Tonini is most interested in the types of symptoms that align with the subtype.

“When comparing those with circadian depression to those who have any other form of depression, we found that [those who fit the circadian profile] have more severe clinical features.”

“The age of onset of depression was younger, and they also report a higher number of depressive episodes, more suicidality, or psychological distress, or somatic complaints. It’s a complex clinical trajectory.”

“We were able to look at a series of genetic risk scores for major mood disorders, including bipolar disorder, but also, for example, ADHD. And then also a series of metabolic and inflammatory markers.”

“We found that circadian depression was associated with higher genetic risk for these markers.”

“To me, that suggests that we are not only capturing depression with bad sleep, but there is a unique underlying biology that's unique to circadian depression.”

Dr Crouse said that this is not the final version of the profile. 

“We're keen to develop it more. I don't think it's ready for prime time to change clinical practice yet, but there's a huge focus on sleep, and sleep disturbance in the field.”

“It's also about what you do during the daytime, how much light exposure you get. We're keen to push this onto the radar.”

The study also found that circadian depression affected young women to a larger degree.

“We found that there were more women who met criteria for circadian depression. In general, women participate in this study more than men,” said Dr Tonini.

“But another thing is that we believe that individuals with circadian depression might have underlying vulnerability risk tied to their high genetic risk marker. And we think that the circadian depression subtype could be linked to postpartum depression as well.”

Circadian depression and bipolar disorder

The links between circadian disturbances and bipolar disorder seem significant.

“It's already been shown that in people who have bipolar disorder, have circadian disturbances as well,” said Dr Tonini.

“It's common for individuals with bipolar disorder to experience seasonality. So, their mood is changing, and their sleep, typically with the seasons. We don't know the proportion of individuals with bipolar disorder who might have a circadian subtype. It's a work that we want to take forward.”

“This information could help us predict who develops bipolar disorder among people who are presenting for depression.”

“There's a diagnostic delay of six to ten years for bipolar disorder after symptom onset. So, there's an important link there,” said Dr Crouse.

The team recently led an expert consensus study regarding what clinicians need to know about chronobiology and chronotherapy for bipolar disorder.

Dr Tonini is currently conducting a clinical trial looking at melatonin as adjunctive to normal treatment to see if melatonin improves depressive symptoms in young people who fit that circadian depression profile.

“We hope that this is going to draw attention to the circadian rhythm and its role in depression and that there's going to be more research on this. There's still so much to explore.”