European Child & Adolescent Psychiatry

, Volume 28, Issue 4, pp 491–504 | Cite as

Blood CRP levels are elevated in children and adolescents with functional neurological symptom disorder

  • Kasia KozlowskaEmail author
  • Jason Chung
  • Bronya Cruickshank
  • Loyola McLean
  • Stephen Scher
  • Russell C. Dale
  • Shekeeb S. Mohammad
  • Davinder Singh-Grewal
  • Mukesh Yajaman Prabhuswamy
  • Ellis Patrick
Original Contribution


There is accumulating evidence that patients with functional neurological symptom disorder (FND) show activation of multiple components of the stress system—the hypothalamic–pituitary–adrenal axis, autonomic nervous system, and brain regions involved in arousal- and emotion-processing. This study aims to examine whether the immune-inflammatory component of the stress system is also activated. C-reactive protein (CRP) blood titre levels were measured in 79 children and adolescents with FND. CRP values ≥ 2 mg/L suggest low-grade inflammation. CRP values > 10 mg/L suggest a disease process. Sixty-six percent of subjects (n = 52) had CRP titres ≥ 2 mg/L. The upward shift in the distribution of CRP levels suggested low-grade inflammation (median CRP concentration was 4.60 mg/L, with 75th and 90th percentiles of 6.1 and 10.3 mg/L, respectively). Elevated CRP titres were not explained by sex, pubertal status, BMI, or medical factors. Confounder analyses suggested that history of maltreatment (χ2 = 2.802, df = 1, p = 0.094, φ = 0.190; β = 2.823, p = 0.04) and a diagnosis of anxiety (χ2 = 2.731, df = 1, p = 0.098, φ = 0.187; β = 4.520, p = 0.061) contributed to elevated CRP levels. Future research will need to identify the origins and locations of immune cell activation and the pathways and systems contributing to their activation and modulation. Because functional activity in neurons and glial cells—the brain’s innate effector immune cells—is tightly coupled, our finding of elevated CRP titres suggests activation of the immune-inflammatory component of the brain’s stress system. A more direct examination of inflammation-related molecules in the brain will help clarify the role of immune-inflammatory processes in FND.


Functional neurological symptoms Conversion disorder Non-epileptic seizures Neuroinflammation Dissociation 



We thank Matthew Frank for his reading of the manuscript as a critical reviewer and Jenny Peat for her help with statistical analyses.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kasia Kozlowska
    • 1
    • 2
    • 3
    Email author
  • Jason Chung
    • 4
    • 5
  • Bronya Cruickshank
    • 1
  • Loyola McLean
    • 6
    • 7
  • Stephen Scher
    • 8
    • 9
    • 10
  • Russell C. Dale
    • 5
    • 11
  • Shekeeb S. Mohammad
    • 5
    • 12
  • Davinder Singh-Grewal
    • 5
    • 13
    • 14
  • Mukesh Yajaman Prabhuswamy
    • 1
    • 15
    • 16
  • Ellis Patrick
    • 17
    • 18
  1. 1.Department Psychological MedicineThe Children’s Hospital at WestmeadWestmeadAustralia
  2. 2.Brain Dynamics Centre Westmead Institute of Medical ResearchWestmeadAustralia
  3. 3.Discipline of Psychiatry and Discipline of Child and Adolescent HealthUniversity of Sydney Medical SchoolSydneyAustralia
  4. 4.Department of Clinical BiochemistryThe Children’s Hospital at WestmeadWestmeadAustralia
  5. 5.Discipline of Child and Adolescent HealthUniversity of Sydney Medical SchoolSydneyAustralia
  6. 6.Westmead Psychotherapy Program for Complex Traumatic DisordersWestern Sydney Local Health DistrictParramattaAustralia
  7. 7.Brain and Mind Centre, and Discipline of PsychiatryUniversity of Sydney Medical SchoolSydneyAustralia
  8. 8.Department of PsychiatryHarvard Medical SchoolBostonUSA
  9. 9.McLean HospitalBelmontUSA
  10. 10.Discipline of PsychiatryUniversity of Sydney Medical SchoolSydneyAustralia
  11. 11.Movement Disorder and Clinical Neuroimmunology Group, Institute for Neuroscience and Muscle ResearchThe Children’s Hospital at WestmeadWestmeadAustralia
  12. 12.Department of Neurology and NeurosurgeryThe Children’s Hospital at WestmeadWestmeadAustralia
  13. 13.Department of RheumatologyThe Children’s Hospital at WestmeadWestmeadAustralia
  14. 14.Discipline of Child and Maternal HealthUniversity of New South WalesSydneyAustralia
  15. 15.Faculty of MedicineUniversity of New South WalesSydneyAustralia
  16. 16.School of Medicine Western Sydney UniversityCampbelltownAustralia
  17. 17.School of Mathematics and StatisticsUniversity of SydneySydneyAustralia
  18. 18.Westmead Institute for Medical ResearchSydneyAustralia

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