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. 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.
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. 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.
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 depression60095-0/fulltext). The trial will also explore whether behavioural strategies for body clock regulation reduce depression.
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