Autonomic, endocrine, and inflammation profiles in functional neurological disorder: A systematic review and meta-analysis
Open accessAbstract
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.
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Hyperarousal is common in FND, exemplified by the observation of panic attack without panic in people with functional seizures, as well as increased sympathetic tone and abnormal startle responses in FND populations.
“Hyperarousal is common in FND; this is exemplified by the observation of 'panic attack without panic' in people with functional seizures, as well as increased sympathetic tone and abnormal startle responses in FND populations.21,46,164,165”
From A new science of emotion: implications for functional neurological disorder (2022) · cites this paper as [46]
The Discussion (page unavailable) reports increased autonomic arousal and more consistent markers of increased sympathetic tone in children and adolescents with FND, but emphasizes heterogeneous findings in adults. Results > Autonomic Findings (page unavailable) reports an increased startle-response probability in one study of functional movement disorder and no group difference in another. The paper does not report the cited observation of a ‘panic attack without panic’ in people with functional seizures, so it does not support that example or the unqualified generalization across FND populations. (LLM, conf=0.87)
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- Authors
- Paredes-Echeverri, S., Maggio, J., Bègue, I., Pick, S., Nicholson, T. R., & Perez, D. L.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Paredes-Echeverri, Sara
- Venue
- The Journal of Neuropsychiatry and Clinical Neurosciences
- Published
- 2022-02
- Volume
- 34
- Issue
- 1
- Pages
- 30-43
- ISSN
- 0895-0172 (ISSN-L)
- 1545-7222
- PMC
- PMC8813876
- OpenAlex
- W3175646162
- Semantic Scholar
- c8f678a43db8fb0e0424b92ef95d0651c0377a35
- Cited by
- 62
- References
- 94
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 21 · 2023: 9 · 2022: 5
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuropsychiatry (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- PubMed Central (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Medical Research Council (MR/V032771/1)
- National Institute of Mental Health (K23MH111983)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- conversion disorder, autonomic dysfunction, endocrine markers, inflammation, resting heart rate, heart rate variability, psychogenic non-epileptic seizures, epileptic seizures, children and adolescents, individual differences, neurobiological mechanisms
- MeSH terms
- Adolescent, Conversion Disorder, Humans, Inflammation, Nervous System Diseases, Seizures, Cohort Studies, Neuroimaging
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