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Cited by 9Sleep and related disordersCircadian rhythm and melatoninTreatment of Major Depression

One-year actigraphy study of sleep and rest-activity rhythms as markers of relapse in depression

Open access
Tonon, Andre C., Nexha, Adile, Cunningham, Jasmyn E. A., d’Eon, Jason, Chakrabarty, Trisha, Farzan, Faranak, Foster, Jane A., Harkness, Kate L. +16 more·2026·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2025.4453
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Abstract

Importance: Given its recurrent nature and burden, major depressive disorder (MDD) warrants reliable methods of relapse prediction. Objective: To determine whether actigraphy-derived parameters, measured over 1 to 2 years, are associated with relapse. Design, Setting, and Participants: This was an observational cohort study with data collection from July 2016 to January 2019. The setting was multicentric. A referred sample of participants from outpatient psychiatric and primary care clinics across Canada were followed up for 1 to 2 years. Participants had a diagnosis of MDD and Montgomery-Åsberg Depression Rating Scale (MADRS) score less than or equal to 14 at baseline. Exposures: Actigraphy-derived parameters measured over 1 to 2 years. Main Outcome and Measures: The primary outcome was relapse, defined as any of the following: MADRS score greater than or equal to 22 for 2 consecutive weeks, psychiatric hospitalization, emergence of suicidal intent or behavior, or antidepressant treatment escalation—all adjudicated by an independent panel. Continuous actigraphy data were averaged every 2 weeks. Results: From a referred sample of 102 adults, 93 participants (mean [SD] age, 39.1 [12.7] years; 58 female [62%]) contributed approximately 32 000 complete actigraphy days (median, 46 weeks). In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; P < .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; P = .01), and higher nighttime activity (HR, 1.86; 95% CI, 1.32-2.62; P < .001) were associated with relapse. In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04-2.98; P = .04) and lower RA (HR, 0.45; 95% CI, 0.21-0.97; P = .046) were associated with relapse, with RA remaining significant even after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; P = .04). Actigraphy significantly differentiated individuals experiencing relapse from those with an ultrastable (MADRS score <14 throughout) and unstable (transient MADRS score, 14-22 without relapse) clinical course. Conclusions and Relevance: Actigraphy measures of sleep phase variability and daily activity amplitude were associated with depressive relapse, supporting actigraphy as a potential scalable biomarker to identify high-risk individuals and enable timely, personalized relapse prevention in MDD.

AI snapshot

Written from the paper’s full text.

TL;DR

In a multicentre observational cohort of adults with remitted major depressive disorder followed for 1–2 years, actigraphy-derived sleep and rest-activity rhythm parameters were associated with depressive relapse. Lower relative amplitude and greater sleep phase variability emerged as the most robust markers, with relative amplitude remaining significant after adjustment for concurrent depressive symptoms.

Key findings

  • In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (HR, 0.46; 95% CI, 0.28–0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29–0.70; P < .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38–0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12–2.80; P = .01), and higher nighttime activity (HR, 1.86; 95% CI, 1.32–2.62; P < .001) were associated with relapse.
  • In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04–2.98; P = .04) and lower RA (HR, 0.45; 95% CI, 0.21–0.97; P = .046) were associated with relapse; RA remained significant after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36–0.98; P = .04).
  • Actigraphy significantly differentiated individuals who relapsed from those with an ultrastable clinical course (MADRS score <14 throughout) and an unstable course (transient MADRS score 14–22 without relapse).

Methods

  • Design: observational, multicentre cohort study with data collection from July 2016 to January 2019; participants followed up for 1 to 2 years.
  • Sample: referred sample from outpatient psychiatric and primary care clinics across Canada; 102 adults with MDD and baseline MADRS ≤14, of whom 93 (mean [SD] age, 39.1 [12.7] years; 58 female [62%]) contributed approximately 32,000 complete actigraphy days (median, 46 weeks).
  • Analysis: actigraphy-derived parameters averaged every 2 weeks; relapse (MADRS ≥22 for 2 consecutive weeks, psychiatric hospitalization, emergence of suicidal intent or behavior, or antidepressant treatment escalation, adjudicated by an independent panel) modelled with Cox models adjusted for age, sex, season, and baseline MADRS, plus time-varying models.

Limitations

  • Not stated in the paper (the available text is the abstract and record; no limitations section is included).
  • Evident from the text: the sample was a referred clinical sample, which may limit generalizability; the abstract does not report model discrimination, calibration, or a validation sample, so the predictive performance of actigraphy as a scalable biomarker is not quantified here.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jamapsychiatry.2025.4453

Cites

58 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

  • Findingown data
    § Abstract

    Baseline higher nighttime activity is associated with relapse in Cox models adjusted for age, sex, season, and baseline MADRS score (HR, 1.86; 95% CI, 1.32-2.62; P < .001).

    “In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; P < .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; P = .01), and higher nighttime activity (HR, 1.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Baseline lower relative amplitude (RA) is associated with relapse in Cox models adjusted for age, sex, season, and baseline MADRS score (HR, 0.45; 95% CI, 0.29-0.70; P < .001).

    “In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; P < .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; P = .01), and higher nighttime activity (HR, 1.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Greater composite phase deviation is associated with relapse in time-varying models (HR, 1.76; 95% CI, 1.04-2.98; P = .04).

    “In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04-2.98; P = .04) and lower RA (HR, 0.45; 95% CI, 0.21-0.97; P = .046) were associated with relapse, with RA remaining significant even after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; P = .04).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Lower relative amplitude (RA) remains significantly associated with relapse after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; P = .04).

    “In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04-2.98; P = .04) and lower RA (HR, 0.45; 95% CI, 0.21-0.97; P = .046) were associated with relapse, with RA remaining significant even after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; P = .04).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract

    Baseline higher wake after sleep onset is associated with relapse in Cox models adjusted for age, sex, season, and baseline MADRS score (HR, 1.77; 95% CI, 1.12-2.80; P = .01).

    “In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; P < .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; P = .01), and higher nighttime activity (HR, 1.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 2

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Abstract

    Relapse was adjudicated by an independent panel.

    “all adjudicated by an independent panel”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data
    § Abstract

    Cox models were adjusted for age, sex, season, and baseline MADRS score.

    “In Cox models adjusted for age, sex, season, and baseline MADRS score”
    Quote in the paperSubstantial claim
2 of 2

  • The paper relies on this without support.

    Major depressive disorder is recurrent and burdensome.

    “Given its recurrent nature and burden, major depressive disorder (MDD) warrants reliable methods of relapse prediction.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The extracted medians showed substantial heterogeneity, ranging from very early relapse in severe or treatment-resistant samples with medians between 53 and 90 days to substantially longer intervals in maintenance-treated populations (218-294 days).

    “The extracted medians showed substantial heterogeneity, ranging from very early relapse in severe or treatment−resistant samples with medians between 53 and 90 days (14, 21, 23, 38) to substantially longer intervals in maintenance−treated populations (218–294 days) (33, 40, 45).”

    From Administrative criteria in the relapse of depressive disorder: a critical appraisal (2026) · cites this paper as [45]

    Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

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Authors
Tonon, A. C., Nexha, A., Cunningham, J. E. A., d’Eon, J., Chakrabarty, T., Farzan, F., Foster, J. A., Harkness, K. L., Hassel, S., Ho, K., Lam, R. W., Milev, R., Minuzzi, L., Müller, D. J., Nunes, A., Parikh, S. V., Quilty, L. C., Rotzinger, S., Soares, C. N., Taylor, V. H., Turecki, G., Uher, R., Kennedy, S. H., & Frey, B. N.
Affiliations
  • Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
  • McMaster University (CA)
  • Dalhousie University (CA)
  • University of British Columbia (CA)
  • Simon Fraser University (CA)
  • The University of Texas Southwestern Medical Center (US)
  • Queen's University (CA)
  • University of Calgary (CA)
  • St. Joseph’s Healthcare Hamilton (CA)
  • University of Toronto (CA)
  • University of Michigan (US)
  • Centre for Addiction and Mental Health (CA)
  • McGill University (CA)
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2026-04-01
Volume
83
Issue
4
Pages
379
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2025.4453
OpenAlex
W7128591209
Semantic Scholar
24c8bf47bd26ad70550fbb0df57e8d87e3030877
Cited by
9
References
58
Citations by year
2026: 9
FWCI
69.01
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
actigraphy, sleep-wake cycle, rest-activity rhythm, depression relapse, major depressive disorder, recurrence prediction, sleep regularity, relative amplitude, sleep efficiency, wake after sleep onset, nighttime activity, seasonal variation, seasonal affective disorder
MeSH terms
Adult, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Recurrence, Rest, Sleep, Cohort Studies, Actigraphy

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