Edward Hopper, Summer Evening, 1947
Broken biological clocks contribute to 1 in 4 cases of depression, and they don’t respond as well to SSRIs
STUDY: Tonini E et al, medRxiv 2026
STUDY TYPE: Cross-sectional study
FUNDING: National Health and Medical Research Council of Australia, Wellcome Trust, private philanthropy
Background
The biological clock has well known links to bipolar disorder, but new research connects it to unipolar depression as well:
- Night owls (circadian phase delay) are more likely to have depression
- Symptoms of jet lag overlap with depression, and social jet lag, where night owls sleep in on weekends and wake up too early on weekdays, is one pathway to depression
- Circadian rhythm therapies – from light therapy to social rhythm therapy – treat unipolar depression
In this study, Australian researchers propose a “circadian” subtype defined by at least three of:
- Oversleeping (hypersomnia) during episodes
- Heavy morning grogginess
- Night owl (evening chronotype or phase delay)
- Going to bed late (late sleep timing)
- Seasonal mood changes
- Sleeping much later on days off (social jet lag)
(Yes, there’s some overlap in those criteria)
The Study
- 11,380 Australian adults with mostly severe, recurrent depression
- Cross sectional comparisons of clinical course, self-rated antidepressant response, and genetic risk scores
Results
1 in 4 met criteria for the circadian subtype (23%). They were younger, more often female, and had their first depression earlier (age 19 vs 23).
They also reported more:
- Bipolar features: Hypomanic and psychotic-like experiences
- Suicidal thoughts and psychological distress
- Physical complaints and weight gain during episodes
- Fatigue and low physical activity
They rated SSRIs and SNRIs as less helpful and reported more side effects on them, although these antidepressant links were modest. Tricyclics and mirtazapine worked about the same in both groups.
The circadian group carried higher genetic risk for evening chronotype, ADHD, bipolar disorder, obesity, insulin resistance, and inflammation. Those effects were small (odds ratios near 1.1).
Limitations
Cross-sectional data built on self-report. It is exploratory, not definitive.
Practice Implications
- Watch for younger patients with depression who sleep late, get depressed in winter, and gets little from serotonergic antidepressants.
- Screen these patients for bipolar before adding another antidepressant, consider light therapy for depression and, to reduce night owl tendencies, low dose melatonin (0.5 mg) or dark therapy 2-3 hours before bed or dark therapy at night.
- The Depression and Bipolar Workbook features circadian-driven behavior therapies.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
