New research may change the way many people with depression are treated

New Australian-led research, published today in The British Journal of Psychiatry, may fundamentally change the way many people with depression are treated.

The study of 11,380 adults diagnosed with depression identified a new subtype caused by circadian rhythm disruption, called circadian depression. Our circadian rhythm, or body clock, controls our daily functions, including sleep and wakefulness, our immune, hormone and metabolic systems, and our ability to focus and mood.

When our body clock is out of alignment with our behaviours, it affects every system.

“Mood is a consequence, not the cause, as is concentration,” says Professor Ian Hickie, co-director of the Brain and Mind Centre at the University of Sydney and a clinical psychiatrist.

The study also found a higher risk of bipolar and ADHD among the circadian subtype, which affected one-quarter of participants and about one in three younger people with depression.

Standard treatment such as selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT) may be ineffective, and SSRIs may even prove harmful for this cohort, the researchers said.

The critical difference in treatment

Sleep disturbance is “almost universal” among people with depression, says Hickie. But circadian disruption goes beyond poor sleep.

Those with circadian depression completed questionnaires and reported at least three of six criteria: seasonal changes in their illness (such as worsening mood in winter and mania in spring); sleeping for long periods during depressive episodes; feeling groggy in the morning; being a night owl; waking up late; and experiencing social jet lag (a mismatch between the time they go to bed and wake up during the week compared with the weekend).

There has been evidence of circadian disruption in depression since the 1960s, but it was believed that if you fixed the depression, those issues would be resolved. This new research challenges that notion.

“Our fundamental starting position is, for significant part of the population – about 30 per cent of those with depression – it’s the other way around,” says Hickie.

“It’s the disturbed body clock that is actually driving the depression. If it’s not attended to, you won’t fix the episode of depression, and you won’t prevent its longer-term recurrence.”

The “critical difference” is in treatment choices, he adds: “The most commonly recommended treatments – cognitive behavioral therapy and, particularly, SSRIs – not only do they not work, they make the circadian type worse.”

Experts believe it has to do with light, the most important factor in setting our body clock each day.

Healthy light patterns, such as bright light during the day and low or no light at night, are associated with a lower risk of depression and other mental illnesses.

“We found in our work that young people with emerging mood disorders seem to be less sensitive to light,” explained the lead author Dr Emiliana Tonini.

This plays out in how people often describe their depression.

“They are three times more likely to use darkness metaphors if they have severe depression,” says Sean Cain, a professor of circadian biology in the College of Medicine and Public Health at Flinders University, who was not involved in the study.

“We think that the circadian system is a brightness detection system, and that people experience depression as a feeling of darkness because this brightness detection system isn’t working.”

SSRIs increase circadian sensitivity to light, which can be useful if people get light at the right time. For night owls, however, who are exposed to bright light late at night, this enhanced sensitivity can exacerbate circadian disruption. Potentially, this exacerbates their symptoms of depression.

Who is affected by the circadian subtype and why?

According to the new study, women, those with severe depression symptoms and those whose symptoms started during adolescence or early adulthood were the most commonly affected.

“The sleep-wake cycle changes radically during adolescence,” Hickie says.

The greater proportion of females experiencing it (80 per cent) is complicated by the fact that more women participated in the study. However, hormonal and environmental changes, such as childbirth, play a role.

“The circadian subtype is particularly relevant to postnatal depression,” he says.

Genetic differences make some people more susceptible to environmental triggers such as adolescence, a new baby, shift work, an infection or regularly staying up late.

“Some of us are much more sensitive and essentially have much more unstable clocks … it’s the extent to which it can be perturbed and does not self-correct,” Hickie explains. “The biology’s fundamentally different, underpinned by differential genetics, but then dependent on environmental exposures.”

Professor Michael Berk, the chair of psychiatry at Deakin University and Barwon Health, says the study is “a very important start” in defining a new subtype, but that further study is needed before it can definitively inform clinical practice.

How it can be treated

Future research will explore whether circadian depression is more responsive to melatonin or melatonin-targeted antidepressants.

“Melatonin is not a sleep drug, it’s a timing drug, and it’s trying to regularise that timing signal,” Hickie says.

If used appropriately, there may still be a place for SSRIs.

“It is riskier,” says Cain, who is recruiting for a study investigating how the effect of SSRIs on light sensitivity impacts their success. “I wouldn’t discount it, but you need to be more careful about the light.”

Treatment would also involve behavioral approaches.

Tonini encourages people to map their sleep regularity and their light exposure to understand their rhythms.

Some smartwatches, such as the Apple Watch, detect time in daylight as well as sleep regularity. But people don’t necessarily need a tracker.

“Even just write it down. Track it over several days and bring that to your clinician to talk about it,” she says.

By waking within the same one-hour window each day, even on weekends, it is possible to improve sleep regularity.

“It’s much easier if you set the wake-up time,” says Hickie. “People tend to do the opposite. They’ll go to bed at 10 o’clock, and then they can’t go to sleep.”

Physical activity, natural daytime light, dim lights at night and stopping eating after the melatonin onset after dark may also help: “It interferes with your insulin regulation.”

“If you want to sleep better tonight, the amount of light exposure you have today and the physical activity will have much bigger impact than starting to worry about it at 10 o’clock at night,” Hickie says.

It’s good health advice for everyone but, Berk says: “It’s particularly useful for people with this pattern of problems.”

Hickie says the research is “fundamental” to effective early intervention: “This offers for the first time, really strong, big study, and really strong genetic evidence in support of it.”

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