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Physical fatigue is a central symptom linking psychological and functional domains in adults with chronic medical conditions, suggesting that targeting fatigue may improve mental health and functional outcomes.

In a baseline analysis of 825 adults with chronic medical conditions, network analysis identified three symptom clusters: mental health, fatigue/frailty, and quality of life, with physical fatigue as the most central node. The findings suggest that fatigue, demoralization, and frailty are interconnected drivers of symptom burden, and targeting fatigue may be a key strategy for improving outcomes.

Last updated: Aug 21, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score32/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Interconnections across physical, psychological, existential, and health-related quality of life patient-reported outcomes in adults with chronic medical conditions: Baseline findings from the eMPower randomized controlled trial.

observational

Johnson E, Hyde A, Vandermeer B, Isley S, Corrick S, Wright G, Ezekowitz J, Zheng Y, Lee-Baggley D, Minckler H, Spiers J, Spence JC, McNeely ML, Thompson S, Ismond K, Tymchuk S, Lai JC, Tandon P · PLOS mental health (2026)

Participants: N/A
Duration: Baseline cross-sectional (from a 12-week trial)
Intervention: No intervention was tested; this is a baseline cross-sectional analysis of the eMPower randomized controlled trial.
Outcome: Network structure of patient-reported outcomes including anxiety, depression, fatigue, frailty, demoralization, sleep disturbance, and quality of life.
Effect Size: N/A
Population: Adults aged ≥18 years with chronic medical conditions (mean age 55.6 ± 12.7 years, 84% female, n=825).

Result:

PubMed: 42616800DOI: 10.1371/journal.pmen.0000694

Mechanism Graph

Physical fatigue is the most central node in the symptom network
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It connects psychological symptoms (e.g., demoralization, depression) with functional domains (e.g., frailty, quality of life)
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Fatigue may act as a bridge that reinforces symptom clustering
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Targeting fatigue could disrupt the cycle and improve overall well-being

Limitations

  • ⚠Cross-sectional design prevents causal inference
  • ⚠Sample is predominantly female (84%), limiting generalizability
  • ⚠Network analysis is exploratory and may not replicate in other populations
  • ⚠Baseline data only; no longitudinal or intervention outcomes reported

Frequently Asked Questions

What is the most central symptom in chronic illness symptom networks?▼

Physical fatigue was identified as the most central node, linking psychological and functional domains.

How many participants were in the eMPower trial baseline analysis?▼

825 adults with chronic medical conditions.

What symptom clusters were found?▼

Three clusters: mental health, fatigue/frailty, and quality of life.

What does this mean for treatment?▼

Targeting fatigue may be an important strategy to improve mental health and functional outcomes in chronic illness.

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References

  1. 1.Johnson E, Hyde A, Vandermeer B, Isley S, Corrick S, Wright G, Ezekowitz J, Zheng Y, Lee-Baggley D, Minckler H, Spiers J, Spence JC, McNeely ML, Thompson S, Ismond K, Tymchuk S, Lai JC, Tandon P. "Interconnections across physical, psychological, existential, and health-related quality of life patient-reported outcomes in adults with chronic medical conditions: Baseline findings from the eMPower randomized controlled trial.." PLOS mental health, 2026. PMID: 42616800 DOI: 10.1371/journal.pmen.0000694
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.