E2 ModerateModerate confidencePEM not requiredCross-SectionalPeer-reviewedMachine draft
Standard · 3 min
Comparing autonomic nervous system function in patients with functional somatic syndromes, stress-related syndromes and healthy controls.
Van Den Houte, Maaike, Ramakers, Indra, Van Oudenhove, Lukas et al. · Journal of psychosomatic research · 2025 · DOI
Quick Summary
This study measured how the nervous system responds to stress in people with ME/CFS and similar conditions, compared to healthy people. Researchers found that patients with ME/CFS and stress-related conditions had their 'stress response system' stuck in overdrive even at rest, and this system didn't properly calm down after stress passed. These findings suggest that autonomic nervous system dysfunction—an imbalance in the automatic systems that control heart rate and other vital functions—may be a common feature across these conditions.
Why It Matters
This study provides objective physiological evidence that ME/CFS involves measurable autonomic nervous system dysfunction, validating patient experiences of abnormal stress responses and poor recovery. Understanding that ANS dysregulation is transdiagnostic—shared across ME/CFS and stress-related syndromes—may guide development of targeted treatments addressing the underlying nervous system imbalance.
Observed Findings
Resting heart rate and skin conductance were higher in both patient groups compared to healthy controls (effect sizes 0.50–0.97).
Heart rate variability was reduced in both patient groups at rest and during recovery phases (effect sizes 0.91–0.98).
Skin conductance response to psychosocial stress was larger in FSS compared to healthy controls (d = 0.71).
Both patient groups showed blunted heart rate increase during stress and slower heart rate recovery afterward compared to controls.
Peripheral skin temperature showed no significant differences between groups.
Inferred Conclusions
Sympathetic nervous system dominance—indicating the stress response system is chronically overactive—is a transdiagnostic feature in both functional somatic syndromes and stress-related syndromes.
Impaired parasympathetic (recovery) function, reflected in reduced HRV during recovery phases, represents a key ANS dysfunction in both patient groups.
ANS dysfunction is present even at baseline rest, suggesting a trait-like abnormality rather than only an exaggerated response to acute stress.
Remaining Questions
Does ANS dysfunction precede symptom onset, develop during illness, or fluctuate with disease severity over time?
What This Study Does Not Prove
This cross-sectional study cannot establish whether ANS dysfunction causes ME/CFS symptoms, results from them, or reflects a shared underlying mechanism. It does not prove that ANS dysfunction is the primary pathology in ME/CFS, nor does it demonstrate that normalizing ANS function would resolve disease symptoms. The study also cannot determine if these ANS patterns are stable over time or change with disease progression.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Can ANS-targeted interventions (such as vagal stimulation or specific breathing techniques) improve symptoms in ME/CFS patients?
What underlying biological mechanisms drive the ANS dysregulation—viral infection, immune dysfunction, central nervous system changes, or other factors?
Do different ME/CFS subtypes or disease stages show different patterns of ANS dysfunction?