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A person with depression might sleep much longer than usual and still wake up feeling exhausted. Later in the evening, when they want to go to bed, they may wake up shaky. Researchers are investigating whether patterns like these can help explain why antidepressants work better for some people than others.
The clue may lie in the body’s internal clock, which helps regulate when one sleeps, wakes, and feels alert.
An Australian study examined 11,380 people, mainly with severe or recurrent depression. About 23% met the researchers’ criteria for a proposed subtype called “circadian depression,” named after the body’s roughly 24-hour internal clock.
Participants needed at least three of six features, including being a night owl, sleeping longer during depression, morning fatigue and seasonal changes in mood or behavior. The other features involve the habit of sleeping and waking up later, and having different sleep schedules on working days and days off.
Compared to other participants, this group reported less benefit and more side effects from two common types of antidepressants, SSRIs and SNRIs, which affect how brain cells communicate through chemical messengers. However, some people with these sleep patterns still report benefiting from these medications.
The researchers also found genetic associations with late bedtimes, reduced sensitivity to insulin, the hormone that helps regulate blood sugar, and a protein involved in inflammation, the immune system’s response to injury or infection. These associations reflect inherited tendencies, rather than evidence that the participants actually had blood sugar problems or inflammation.
The results are preliminary. Participants recalled their symptoms and medication experiences, and those in the suggested group generally had more severe depression. The researchers did not measure their internal clock or establish cause and effect.
Some features overlap with recognized forms of depression, so it remains unclear whether this is a distinct subtype. All participants had European genetic ancestry, limiting the extent to which the findings can be applied. The 23% figure cannot therefore be assumed to represent everyone with depression.
How the body clock affects mood
The body clock coordinates roughly 24-hour cycles, known as circadian rhythms, that affect sleepiness, body temperature and hormones, the chemical messengers that help regulate the body. Light reaching the eye helps keep this clock aligned with day and night. Food and physical activity also provide timing cues.
When internal timing collides with daily demands, sleep can suffer. Someone whose clock is running late may feel alert at midnight but have to get up for work while their body is still expecting sleep. Being a night owl is not necessarily a problem. Persistent disorder is the concern.
Sleep and mental health can reinforce each other. Disturbed sleep can worsen depression, while depression and stress can disrupt sleep and daily routines.
One possible link involves the brain systems that regulate emotions and reward, including the ability to enjoy pleasurable experiences. Animal experiments suggest that disruption of the body clock can affect these systems and produce depressive-like behavior.
In small laboratory experiments, researchers changed the sleep schedules of shift workers and people who did not work shifts. When their sleep and wake times were out of step with their internal clocks, participants reported worse moods. They were not recruited because they had depression, and temporary low mood is different from clinical depression.
Conventional antidepressants may leave a timing problem untreated, but that remains a hypothesis. The Australian study did not test body-clock treatments, and its findings cannot determine whether someone with disrupted rhythms would benefit more from an alternative medicine.
Could light therapy help?
Light therapy involves sitting near a specially designed bright light box at a scheduled time, often in the morning. Morning light can shift a late running body clock earlier, helping one feel sleepy and wake up earlier.
Read more: Why morning blue light therapy could improve sleep and daily activity in older adults
The treatment is used for seasonal affective disorder, depression that follows a seasonal pattern, often during the dark months. Evidence suggests that it may also help with depression that does not have a seasonal pattern.
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A review of 11 clinical trials involving 858 people investigated bright light therapy for non-seasonal depression, including bipolar depression. Bipolar disorder involves depression alongside episodes of unusually elevated or irritable mood and increased energy.
In studies reporting remission, about 41% of people receiving bright light improved enough to fall below the threshold for depression, compared with 24% who received dim light or treatment without bright light.
But these studies did not select people with the proposed circadian subtype, so they cannot tell us whether this group benefits more. Light can also affect mood through brain pathways separate from the body clock.
Timing and medical guidance important. The light may fade the clock earlier or later depending on when it is used. People with bipolar disorder need special supervision, as light therapy can sometimes trigger unusually elevated or irritable mood.
Regular waking times, daytime activity and meals can also support daily rhythms. Melatonin, a hormone that rises in the evening and biologically signals night, can help to fade a delayed clock if carefully adjusted. However, studies have not established melatonin supplements as an effective depression treatment.
Towards more personalized treatment
Could measuring an internal clock help doctors choose treatments? Wrist-worn activity monitors can estimate sleep patterns, while saliva samples taken throughout the evening can show when melatonin begins to rise, providing a more direct measure of internal timing.
Researchers need to establish whether the proposed group really has different biological rhythms, then test whether the choice of treatment based on these measurements helps people recover faster.
For now, sleep patterns cannot reliably predict which antidepressants will work best, and the results do not provide a reason to change prescriptions without medical advice.
If future studies confirm a benefit, a prescription for depression may one day specify when to get the light as carefully as what medicine to take.
