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

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Abstract

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.

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Acknowledgements

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

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Authors and Affiliations

  1. Department Psychological Medicine, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Kasia Kozlowska, Bronya Cruickshank & Mukesh Yajaman Prabhuswamy

  2. Brain Dynamics Centre, Westmead Institute of Medical Research, Westmead, NSW, Australia

    Kasia Kozlowska

  3. Discipline of Psychiatry and Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia

    Kasia Kozlowska

  4. Department of Clinical Biochemistry, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Jason Chung

  5. Discipline of Child and Adolescent Health, University of Sydney Medical School, Sydney, NSW, Australia

    Jason Chung, Russell C. Dale, Shekeeb S. Mohammad & Davinder Singh-Grewal

  6. Westmead Psychotherapy Program for Complex Traumatic Disorders, Western Sydney Local Health District, Building 112, Cumberland Hospital Campus, Parramatta BC, Locked Bag 7118, Parramatta, NSW, 2124, Australia

    Loyola McLean

  7. Brain and Mind Centre, and Discipline of Psychiatry, University of Sydney Medical School, Sydney, NSW, Australia

    Loyola McLean

  8. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Stephen Scher

  9. McLean Hospital, Belmont, MA, USA

    Stephen Scher

  10. Discipline of Psychiatry, University of Sydney Medical School, Sydney, NSW, Australia

    Stephen Scher

  11. Movement Disorder and Clinical Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Russell C. Dale

  12. Department of Neurology and Neurosurgery, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Shekeeb S. Mohammad

  13. Department of Rheumatology, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, 2145, Australia

    Davinder Singh-Grewal

  14. Discipline of Child and Maternal Health, University of New South Wales, Sydney, NSW, Australia

    Davinder Singh-Grewal

  15. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    Mukesh Yajaman Prabhuswamy

  16. School of Medicine, Western Sydney University, Campbelltown, NSW, Australia

    Mukesh Yajaman Prabhuswamy

  17. School of Mathematics and Statistics, University of Sydney, F07 – Carslaw Building, Sydney, NSW, 2006, Australia

    Ellis Patrick

  18. Westmead Institute for Medical Research, Sydney, NSW, Australia

    Ellis Patrick

Authors
  1. Kasia Kozlowska
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  2. Jason Chung
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  3. Bronya Cruickshank
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  4. Loyola McLean
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  5. Stephen Scher
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  6. Russell C. Dale
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  7. Shekeeb S. Mohammad
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  8. Davinder Singh-Grewal
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  9. Mukesh Yajaman Prabhuswamy
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  10. Ellis Patrick
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Corresponding author

Correspondence to Kasia Kozlowska.

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Kozlowska, K., Chung, J., Cruickshank, B. et al. Blood CRP levels are elevated in children and adolescents with functional neurological symptom disorder. Eur Child Adolesc Psychiatry 28, 491–504 (2019). https://doi.org/10.1007/s00787-018-1212-2

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  • DOI: https://doi.org/10.1007/s00787-018-1212-2

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