A quarter of depression cases are caused by people’s body clocks being out of whack, a large study suggests. This newly identified “circadian depression” responds poorly to standard antidepressants, but might be eased by taking melatonin or adopting behavioural strategies, like going outside in the early morning sun.
“The coordination of [your body clocks] underpins your mood, your metabolism, your concentration, your sleep-wake cycle and many other key factors,” says Ian Hickie at the University of Sydney. “When it’s well, you feel really well, you get up in the morning full of energy. When it’s off, you feel jet-lagged all the time, you feel tired, you feel exhausted, you gain weight, you can’t concentrate, you sleep poorly and your behaviour changes.”
Hickie and his colleagues asked more than 10,000 people in Australia with severe, recurrent depression to fill out surveys about their sleep patterns and other characteristics, such as whether their symptoms change seasonally. The participants also provided saliva samples for DNA analysis.
Of these participants, 23 per cent were identified as having circadian depression. This meant they exhibited at least three of six signs of body clock dysregulation: being an “evening type”, going to sleep later than most people, feeling very tired when getting up regardless of sleep duration, sleeping more during bouts of depression, sleeping in late on non-work days, and experiencing strong seasonal changes in mood, energy, sleep and appetite. “It’s not only about the quantity or the amount of sleep, it’s really about the rhythm and the regularity of sleep,” says team member Emiliana Tonini, also at the University of Sydney.
Those with circadian depression tended to have more severe symptoms than those with non-circadian depression, including more suicidal thoughts. They also developed symptoms at an earlier age – the average age of onset was 18 in the circadian-depression group and 23 in the non-circadian group.
Body clock dysregulation and the resulting mood disturbances may be caused by genetic factors, the study found. The participants with circadian depression were more likely to have genetic variants linked to sleep problems, higher body weight, inflammatory markers and ADHD. “There is an underlying biology that is quite distinct from other forms of depression,” says Tonini.
Another contributing factor may be our modern lifestyles, says Hickie. Our body clocks need to be reset each morning by light exposure to maintain steady, 24-hour rhythms and can be destabilised by artificial light exposure at times when we would have historically been in the dark, he says. “We live in the 21st century, which says, you know, ‘Stay inside, be on a computer all day, avoid the light and then stay up at night and expose yourself to light’”. This is “a complete reverse of what we’re built for”.
The participants identified as having circadian depression reported less efficacy and more side effects when they took common antidepressants like selective serotonin reuptake inhibitors. This may be because these SSRIs target a form of depression related to the neurotransmitter serotonin.
The researchers are about to launch a clinical trial to investigate whether taking a synthetic form of the hormone melatonin, which regulates sleep-wake cycles, might be more effective for treating circadian depression. They previously found that an antidepressant called agomelatine, which mimics melatonin’s effects in the brain, improved sleep and reduced general depression.
The trial will also explore whether behavioural strategies for body clock regulation reduce depression. These include waking up at the same time every morning around sunrise and going outside, spending time outside again in the middle of the day when the sun is brightest, and having regular mealtimes and exercise times during daylight hours.
Once it gets dark, Hickie recommends not eating large meals, exercising or being exposed to bright lights. “They are all the wrong signals,” he says.
Aside from helping with depression, rejigging body clocks may also reduce inflammation and promote healthy weight, says Hickie. He hopes that, in the future, early identification of circadian depression will allow people to be treated more effectively and spare them from taking medications that are inappropriate for them. “If you get on the right track first off, you’re more likely to get out of the hole you’re in and more likely to have better longer-term mental health, but also physical health,” he says.
The findings are “really useful because they advance the field in terms of understanding the whole circadian rhythm aspect of depression and how it might be related to biological measures like genetics and inflammatory markers”, says Colleen Loo at the University of New South Wales in Sydney.
However, more research is needed before circadian depression can be formally recognised as a new subtype of depression, says Loo. “As a clinical psychiatrist, I don’t think it’s time for us to say, ‘Right, based on this, we’re going to say that, if you have these symptoms, we should treat you with this medication rather than that medication,’” she says.
Nevertheless, people with depression could consider trying melatonin and behavioural strategies in addition to their current treatments if they believe their body clocks aren’t functioning optimally, says Loo. Melatonin is available only on prescription in the UK and Australia, but not in the US. “Melatonin is a safe medication and things like low lighting before bed is sensible anyway,” says Loo. “All clinicians should be talking to patients about these things if they have sleep disturbances.”
Need a listening ear? UK Samaritans: 116123; US 988 Suicide & Crisis Lifeline: 988; hotlines in other countries.