• Roxanne C Keynejad, Thomas Frodl, Richard Kanaan, Carmine Pariante, Markus Reuber, and Timothy R Nicholson.
• Section of Women's Mental Health, Health Service and Population Research Department, Institute of Psychiatry Psychology & Neuroscience, King's College London, London, UK roxanne.keynejad@kcl.ac.uk.
• J. Neurol. Neurosurg. Psychiatr. 2019 Jul 1; 90 (7): 813-821.

AbstractAt the interface between mind and body, psychiatry and neurology, functional neurological disorder (FND) remains poorly understood. Formerly dominant stress-related aetiological models have been increasingly challenged, in part due to cases without any history of past or recent trauma. In this perspective article, we review current evidence for such models, and how research into the role of traumatic stress in other disorders and the neurobiology of the stress response can inform our mechanistic understanding of FND. First, we discuss the association between stress and the onset or exacerbation of a variety of physical and mental health problems. Second, we review the role of hypothalamic-pituitary-adrenal axis dysfunction in the neurobiology of ill-health, alongside evidence for similar mechanisms in FND. Third, we advocate a stress-diathesis model, in which biological susceptibility interacts with early life adversity, where FND can be precipitated by traumatic events later in life and maintained by psychological responses. We hypothesise that greater biological susceptibility to FND is associated with less severe remote and recent stress, and that FND precipitated by more severe stress is associated with lower biological vulnerability. This would explain clinical experience of variable exposure to historical and recent traumatic stress among people with FND and requires empirical investigation. A testable, evidence-based stress-diathesis model can inform nuanced understanding of how biological and psychological factors interact at the individual level, with potential to inform personalised treatment pathways. Much-needed research to establish the aetiology of FND will enhance clinical care and communication, facilitate effective treatment and inform prevention strategies.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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