A Fourth of People With Severe Depression May Have a Body-Clock Subtype

Keypoints:

• A study of 11,380 people with severe depression appeared in The British Journal of Psychiatry on 21 October
• 2,604 people, about 23%, met at least three of six proposed criteria for "circadian depression"
• The group had earlier onset and more severe symptoms
• They also had a higher genetic risk for several conditions and late sleep habits
• Researchers plan to test melatonin and daily-routine changes

Researchers from Australia say a quarter of people with severe depression may share a body-clock subtype. They call it circadian depression. The study used data from 11,380 participants in the Australian Genetics of Depression Study. Of them, 2,604 met at least three of six criteria for the subtype. The concept was first proposed in 2021 by a team including Ian Hickie of the University of Sydney.

The six criteria center on timing. They include symptoms that change with the seasons as day length shifts, and a sleep midpoint that is later than in the general population. They also include social jet lag. That means a person's sleep midpoint on workdays differs by several hours from the midpoint on days off. Typical features are disrupted sleep, low energy and reduced activity during the day.

The group looked different from other participants. People in the circadian group had symptoms that started earlier in life and tended to be more severe. Their genetic profile also stood out. They carried a higher genetic risk for depression, anxiety, ADHD and bipolar disorder. They also had a higher genetic risk for higher body weight, insulin resistance, inflammation, insomnia and late sleep habits.

Treatment responses were reported differently. Participants in the circadian group said common antidepressants, such as selective serotonin reuptake inhibitors, helped them less. They also reported more side effects, including drowsiness, nausea, anxiety and weight gain. Co-author Emiliana Tonini of the University of Sydney said the findings show it is not just depression with bad sleep. The underlying biology appears distinct.

Experts urge caution. The participants were all of European ancestry, and treatment responses were self-reported. The subtype is not yet a formal diagnosis. More evidence is needed before treatment guidelines change. People taking antidepressants should not change their treatment because of this study, since the findings describe groups and not individuals.

The next step is testing. Hickie says light exposure, movement and eating patterns help regulate the body's 24-hour clock. Researchers plan trials of melatonin and routine changes for this group. If a body clock can shape how depression looks and responds to treatment, timing may belong in the diagnosis.