One in four people with severe depression may have a dysregulated body clock

Sam Hockey's mental health journey stretches across more than two decades.

A diagnosis of post-traumatic stress disorder and insomnia at age eight, after being trapped in a house fire,and then being "horribly bullied" in high school had a significant impact on his mental health.

"I overslept as a way of escapism but then I would also not wake up rested," he said.

"I had intense low energy, and when it came to school, my cognitive function wasn't great, then didn't have the mental or emotional capacity to really combat the bullying."

In hindsight, Mr Hockey said these sleep symptoms were the first signs he had circadian depression, a proposed new subtype of the mood disorder from experts at the University of Sydney's Brain and Mind Centre.

A new Australian study, published today in The British Journal of Psychiatry, suggests about one in four people with severe, recurrent or persistent depression, like Mr Hockey, have this subtype.

Researchers say the subtype is linked to the body's internal clock and people with it often report being a "night owl" or waking up feeling very tired.

Lead researcher Emiliana Tonini from the Brain and Mind Centre said the findings had implications for early intervention and treatment.

"Depression is not a uniform illness and understanding the characteristics of different subtypes means that we can give people earlier access to treatments that will be most effective for them," she said.

What is circadian depression?

According to the World Health Organization, about 322 million people globally have depression, a mood disorder which causes persistent sadness, emptiness or loss of interest in previously enjoyable activities.

In this new study, Dr Tonini and her team looked at clinical and genetic data from 11,380 Australians with severe, recurrent or persistent depression who took part in a long-running national depression study.

They found 2,604 people in this group met the criteria for circadian depression as they self-reported three or more of the following:

• Waking up very tired
• Being a "night owl"
• Experiencing a seasonal pattern of illness
• Sleeping later
• Sleeping more when depressed
• Experiencing "social jet lag" where sleep timings vary greatly between work days and free days

Patients with circadian depression also reported "more severe mental health symptoms" than those with non-circadian depression, Dr Tonini said.

This included an earlier age of onset, more severe symptoms like mania, suicidality, weight gain during mental health episodes and more complex mental health trajectories.

The research also suggests people with circadian depression may have a different genetic profile to those with non-circadian depression, including a higher genetic risk for attention deficit hyperactivity disorder (ADHD).

Philip Mitchell, scientia professor of psychiatry at the University of New South Wales who did not contribute to the research, said more research was needed before circadian depression could be classified as its own subtype.

"At the moment it's not reaching the bar where this could enter clinical practice, but I think this is very thought-provoking for the field," he said.

Professor Mitchell said there was overlap between the features of circadian depression and a recognised subtype called atypical depression, which indicated the need for a clearer distinction between the two.

And he added that more international research was needed to support the Australian findings.

How is sleep and depression connected?

The study suggests circadian depression is linked to the body's 24-hour internal clock which regulates the sleep-wake cycle.

Brain and Mind Centre co-director and clinical psychiatrist Ian Hickie said this internal clock underpinned "your mood, your metabolism, your concentration, your sleep-wake cycle and many other key factors as well".

Professor Hickie said light exposure, movement and eating patterns were important to help regulate the body's 24-hour internal clock, or circadian rhythm.

"It isn't just sleep, it's not just about sleeping better," he said.

Shanthakumar Wilson Rajaratnam, professor of sleep and circadian medicine at Monash University who did not contribute to the study, said a dysregulated circadian system could impact a range of different body systems, including cardiovascular function.

Criteria used to define circadian depression, such as being a "night owl" or waking up very tired, might not solely be driven by circadian dysfunction, he said.

Professor Rajaratnam said symptoms that might explain circadian dysfunction could also be explained by disturbed sleep.

"Symptoms and sleep complaints have a high degree of comorbidity and overlap with depression and mood disturbances," he said.

What does this mean for treatment?

According to this study, patients with circadian depression may be less responsive to traditional antidepressants.

However, Dr Tonini said this finding came from self-reported data, which meant more research was needed to test the efficacy of traditional antidepressants in this proposed subgroup.

She said targeted treatments —such as melatonin, melatonin-targeted antidepressants, light therapy and behavioural changes —may improve outcomes for patients with circadian depression.

More than two decades after his first mental health diagnosis, things have greatly improved for Mr Hockey.

As a youth lived-experience researcher with the Brain and Mind Centre, he was one of the co-authors on the new study.

He said that understanding more about his 24-hour internal clock earlier in life would have saved "a lot of grief, a lot of trouble, a lot of money, and hardship".

But learning about circadian patterns and making behavioural changes, such as putting his bedside light on a timer, had helped him regulate his body clock.

Professor Mitchell and Professor Rajaratnam agreed that there was enough evidence in this study to warrant asking patients with depression about their circadian patterns.

But this was in addition to, not instead of, traditional treatment options.

"It's important to address the sleep and circadian complaints in patients that are presenting with psychiatric disorders, including depression, as well as treating the depression symptoms," Professor Rajaratnam said.