Elsevier

Biological Psychology

Volume 82, Issue 2, October 2009, Pages 101-110
Biological Psychology

Review article
As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders

https://doi.org/10.1016/j.biopsycho.2009.05.002Get rights and content

Abstract

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD) = −0.32, 95% CI −0.63 to −0.01, p = 0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry = 0.01, 95% CI −0.34 to 0.36, p = 0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.

Introduction

Functional somatic disorders (FSD) are syndromes of related complaints with no known underlying organic pathology. The ‘big three’ are chronic fatigue syndrome (CFS), fibromyalgia (FM) and irritable bowel syndrome (IBS) and it has been thought that their similarities outweigh their differences (Wessely et al., 1999). An important theory about the etiology of FSD is the chronic stress hypothesis: stress-sensitive personality traits, stressful life events and chronic difficulties have part in the development of FSD (van Houdenhove et al., 2005, Deary et al., 2007). Dysfunction of the autonomic nervous system (ANS) is a potential mechanism that connects psychosocial stress to FSD. It has been shown that the ANS is influenced by intense acute, repetitive and chronic psychosocial stress (Sloan et al., 1994, Dishman et al., 2000, Schommer et al., 2003). When the load of stressors in an individual is too large, when the ANS is chronically addressed, or when the capacity of the ANS to adjust is diminished, ANS dysfunction may develop (Chrousos and Gold, 1992). As the ANS innervates several organs, sensation and misinterpretation of generated peripheral physiological arousal due to dysfunction may contribute to experience of functional somatic symptoms (Sharpe and Bass, 1992, Rief and Barsky, 2005). A narrative review of 34 studies suggests that decreased parasympathetic nervous system (PNS) activity could be associated with presence of CFS, FM, and IBS, however, findings are not fully consistent (Tak and Rosmalen, 2007). It remains to be elucidated why it seems that the severity of PNS alterations varies both within and among the three FSD. Disparities in methodological study quality, such as biased selection of control subjects, no exclusion of cardio-active medication use, inaccurate PNS activity measures, and lack of adjustment for potential confounders may have contributed to the mixed findings.

The aims of the current study are to assess whether FSD are characterized by alterations in PNS activity and to examine whether this association is moderated by the type of FSD. Furthermore, we aim to study whether methodological study quality correlates with study findings. Usually, cardiac ANS function is non-invasively assessed by measurement of heart rate variability (HRV), a measure of interbeat interval fluctuations in heart rate. Commonly used indices are frequency domain and time domain measures. Due to unstandardized environmental influences, ambulatory HRV recordings during 24-h are not comparable with those of short duration in a situation (TFESC, 1996). Reliability of HRV measurements performed during interventions such as tilt or pharmacological stimulation is generally poorer than when measured at rest (Sandercock et al., 2005). Therefore, we selected only studies reporting on resting PNS activity in the frequency domain (HRV-HF), defined at 0.15–0.40 Hz, or in the time domain (the root mean square of differences between successive interbeat intervals (RMSSD)), both recommended as preferential PNS measures (TFESC, 1996). Short term HRV-HF and RMSSD have a clear physiological basis and are highly correlated (Berntson et al., 1997).

We present the first meta-analysis and systematic review of methodological study quality on the association between resting HRV and FSD.

Section snippets

Search strategy

Relevant articles were identified by searching the databases of Medline (1966–June 2007), Embase (1980–June 2007), PsycINFO (1960–June 2007) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982–June 2007). For searching Medline with the PubMed interface, a search string was formulated. The first component consisted of the FSD chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome and synonyms. The second component consisted of the terms autonomic nervous system,

Search results and description of studies

The search strategy identified a total of 271 references. Another six references were retrieved from searching reference lists. The consultation of experts about (un)published data did not lead to additional inclusion of articles. After applying inclusion criteria, 54 references were left for full text reading. Applying our exclusion criteria led to a further exclusion of 31 articles, with as most frequent reason double publication of data on the same subjects in different articles. In summary,

Discussion

The aims of the current study were to assess whether FSD are characterized by alterations in PNS activity and to examine whether this association was moderated by the type of FSD or influenced by methodological study quality. Meta-analysis of 14 published studies revealed lower PNS activity in FSD patients compared to controls that was not significantly moderated by type of FSD (i.e., CFS, FM or IBS). The reliability of all summary estimates in this meta-analysis is, however, significantly

Acknowledgements

We thank the experts (Dr. S. Elsenbruch, Prof. W. Orr, Prof. M.M. Heitkemper, Dr. R.L. Burr, Dr. K. Cain, Dr. M. Martinez-Lavin, and Dr. K. Yoshiuchi) for their contribution to the quality tool and Dr. Ir. A.M. van Roon for his methodological advices regarding heart rate variability measurements.

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