A group of sleep and circadian researchers from the University of Sydney, Harvard Medical School, the National Institute of Mental Health, and six other institutions has formally proposed that circadian rhythms and their behavioral outputs be included as biomarkers in the forthcoming DSM-6.
Published as a letter in the American Journal of Psychiatry, the proposal responds to recent work by Cuthbert and colleagues on the future of psychiatric nosology. The authors argue that circadian disruption is not merely a symptom of mental illness but a measurable, mechanistically grounded biological process that cuts across diagnostic categories.
Key points
Circadian rhythms regulate mood, cognition, sleep, energy, and social behavior through the master clock in the suprachiasmatic nucleus and downstream molecular oscillators in nearly every cell. Disruption, whether through genetic variation in clock genes, environmental misalignment (shift work, social jet lag), or disease-related pathophysiological changes, is consistently observed in depressive disorders, bipolar disorder, and other psychiatric conditions.
The letter proposes that behavioral outputs of the circadian system, including rest-activity rhythms measured by actigraphy, dim-light melatonin onset, daily mood and energy patterns, meet the criteria for biomarkers as defined in the NIMH Research Domain Criteria framework. These measures are non-invasive, scalable via wearables, and grounded in a well-characterized biology that spans genetics, neurobiology, and behavior.
Specific applications suggested include predicting lithium response in bipolar disorder, distinguishing bipolar depression from unipolar depression, and identifying circadian-based subtypes of major depressive disorder that may respond preferentially to chronotherapeutic interventions (light therapy, timed melatonin, sleep scheduling).
Why it matters
Psychiatric diagnosis remains entirely symptom-based. The inclusion of circadian biomarkers in DSM-6 would mark a shift toward biologically informed classification, not replacing clinical assessment but supplementing it with objective, dimensional measurements. For patients, this could mean more precise diagnosis, treatment selection based on circadian phenotype rather than trial-and-error, and a framework that positions sleep and circadian health as central to mental health care rather than peripheral.
Source
Crouse JJ, et al. Proposal for Circadian Rhythms and Their Behavioral Outputs as Biomarkers in DSM-6: Response to Cuthbert et al. Am J Psychiatry. 2026 Jun 18. DOI: 10.1176/appi.ajp.20260227. PMID: 42310503.