Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Winter;34(1):30-43.
doi: 10.1176/appi.neuropsych.21010025. Epub 2021 Oct 29.

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis

Sara Paredes-Echeverri  1 , Julie Maggio  1 , Indrit Bègue  1 , Susannah Pick  1 , Timothy R Nicholson  1 , David L Perez  1
Affiliations
Meta-Analysis

Autonomic, Endocrine, and Inflammation Profiles in Functional Neurological Disorder: A Systematic Review and Meta-Analysis

Sara Paredes-Echeverri et al. J Neuropsychiatry Clin Neurosci. 2022 Winter.

Erratum in

  • Correction to Paredes-Echeverri et al.
    [No authors listed] [No authors listed] J Neuropsychiatry Clin Neurosci. 2023 Summer;35(3):315. doi: 10.1176/appi.neuropsych.21010025correction. J Neuropsychiatry Clin Neurosci. 2023. PMID: 37448310 No abstract available.

Abstract

Objective: Functional neurological disorder (FND) is a core neuropsychiatric condition. To date, promising yet inconsistently identified neural circuit profiles have been observed in patients with FND, suggesting that gaps remain in our systems-level neurobiological understanding. As such, other important physiological variables, including autonomic, endocrine, and inflammation findings, need to be contextualized for a more complete mechanistic picture.

Methods: The investigators conducted a systematic review and meta-analysis of available case-control and cohort studies of FND. PubMed, PsycINFO, and Embase databases were searched for studies from January 1, 1900, to September 1, 2020, that investigated autonomic, endocrine, and inflammation markers in patients with FND. Sixty-six of 2,056 screened records were included in the review, representing 1,699 patients; data from 20 articles were used in the meta-analysis.

Results: Findings revealed that children and adolescents with FND, compared with healthy control subjects (HCs), have increased resting heart rate (HR); there is also a tendency toward reduced resting HR variability in patients with FND across the lifespan compared with HCs. In adults, peri-ictal HR differentiated patients with functional seizures from those with epileptic seizures. Other autonomic and endocrine profiles for patients with FND were heterogeneous, with several studies highlighting the importance of individual differences.

Conclusions: Inflammation research in FND remains in its early stages. Moving forward, there is a need for the use of larger sample sizes to consider the complex interplay between functional neurological symptoms and behavioral, psychological, autonomic, endocrine, inflammation, neuroimaging, and epigenetic/genetic data. More research is also needed to determine whether FND is mechanistically (and etiologically) similar or distinct across phenotypes.

Keywords: Conversion Disorder; Cortisol; Functional Neurological Disorder; Heart Rate; Inflammation; Psychogenic Nonepileptic Seizures.

PubMed Disclaimer

Conflict of interest statement

Disclosures / Conflicts of Interest:

D.L.P. has received honoraria for continuing medical education lectures in functional neurological disorder and is on the editorial board of Epilepsy & Behavior. All other authors do not report any disclosures / conflicts of interest.

Figures

Figure 1.
Figure 1.. Flow Diagram of Article Selection.
FND, Functional Neurological Disorder.
Figure 2.
Figure 2.. Forest Plot of Baseline Heart Rate Mean Difference between Patients with Functional Neurological Disorder vs. Healthy Controls.
Panel A. Forest plot of baseline heart rate mean difference between functional neurological disorder vs. healthy control cohorts. Panel B. Forest plot of baseline heart rate mean difference between functional neurological disorder vs. healthy control cohorts, when the FND-seiz cohort in Demartini et al., 2016 is removed based on the sensitivity analysis results (see Supplementary Figure 1). FND, Functional Neurological Disorder; HC, Healthy Control; CI, Confidence Interval; Mean Diff, Mean Difference; θ, effect size; Q, homogeneity; H2, heterogeneity; I2, variation; τ2, variability; REML, restricted maximum likelihood model.
Figure 2.
Figure 2.. Forest Plot of Baseline Heart Rate Mean Difference between Patients with Functional Neurological Disorder vs. Healthy Controls.
Panel A. Forest plot of baseline heart rate mean difference between functional neurological disorder vs. healthy control cohorts. Panel B. Forest plot of baseline heart rate mean difference between functional neurological disorder vs. healthy control cohorts, when the FND-seiz cohort in Demartini et al., 2016 is removed based on the sensitivity analysis results (see Supplementary Figure 1). FND, Functional Neurological Disorder; HC, Healthy Control; CI, Confidence Interval; Mean Diff, Mean Difference; θ, effect size; Q, homogeneity; H2, heterogeneity; I2, variation; τ2, variability; REML, restricted maximum likelihood model.
Figure 3.
Figure 3.. Forest Plot of Peri-ictal Heart Rate Mean Difference between Patients with Functional Seizures vs. Epileptic Seizures.
FND, Functional Neurological Disorder; ES, Epileptic Seizures; CI, Confidence Interval; Mean Diff, Mean Difference; θ, effect size; Q, homogeneity; H2, heterogeneity; I2, variation; τ2, variability; REML, restricted maximum likelihood model.
Figure 4.
Figure 4.. Forest Plot of Baseline Heart Rate Variability Standardized Mean Difference between Patients with Functional Neurological Disorder vs. Healthy Controls.
FND, Functional Neurological Disorder; HC, Healthy Controls; rMSSD, Root Mean Square of Successive Differences; CI, Confidence Interval; St. Mean Diff, Standardized Mean Difference; θ, effect size; Q, homogeneity; H2, heterogeneity; I2, variation; τ2, variability; REML, restricted maximum likelihood model.
Figure 5.
Figure 5.. Forest Plot of Cortisol Standardized Mean Difference between Patients with Functional Neurological Disorder, Epilepsy and Healthy Controls.
Panel A. Forest plot of baseline cortisol standardized mean difference between functional neurological disorder patients and healthy controls. Panel B. Forest plot of baseline cortisol standardized mean difference between functional neurological disorder and epilepsy patients. FND, Functional Neurological Disorder; HC, Healthy Controls; ES, Epileptic Seizures; St. Mean Difference, Standardized Mean Difference; θ, effect size; Q, homogeneity; H2, heterogeneity; I2, variation; τ2, variability; REML, restricted maximum likelihood model.
Figure 5.
Figure 5.. Forest Plot of Cortisol Standardized Mean Difference between Patients with Functional Neurological Disorder, Epilepsy and Healthy Controls.
Panel A. Forest plot of baseline cortisol standardized mean difference between functional neurological disorder patients and healthy controls. Panel B. Forest plot of baseline cortisol standardized mean difference between functional neurological disorder and epilepsy patients. FND, Functional Neurological Disorder; HC, Healthy Controls; ES, Epileptic Seizures; St. Mean Difference, Standardized Mean Difference; θ, effect size; Q, homogeneity; H2, heterogeneity; I2, variation; τ2, variability; REML, restricted maximum likelihood model.
See this image and copyright information in PMC

References

    1. Perez DL, Aybek S, Popkirov S, Kozlowska K, Stephen CD, Anderson J, et al. A Review and Expert Opinion on the Neuropsychiatric Assessment of Motor Functional Neurological Disorders. J Neuropsychiatry Clin Neurosci. 2021;33(1):14–26. - PubMed
    1. Stone J, Carson A, Duncan R, Roberts R, Warlow C, Hibberd C, et al. Who is referred to neurology clinics?--the diagnoses made in 3781 new patients. Clin Neurol Neurosurg. 2010;112(9):747–51. - PubMed
    1. Stephen CD, Fung V, Lungu CI, Espay AJ. Assessment of Emergency Department and Inpatient Use and Costs in Adult and Pediatric Functional Neurological Disorders. JAMA Neurol. 2020. - PMC - PubMed
    1. Gelauff JM, Carson A, Ludwig L, Tijssen MAJ, Stone J. The prognosis of functional limb weakness: a 14-year case-control study. Brain. 2019;142(7):2137–48. - PubMed
    1. Baslet G, Bajestan SN, Aybek S, Modirrousta M, JP DCP, Cavanna A, et al. Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures: A Report From the American Neuropsychiatric Association Committee on Research. J Neuropsychiatry Clin Neurosci. 2021;33(1):27–42. - PubMed