Genetic and Early-Life Vulnerability in Functional Neurological Disorder: A Large-Scale Retrospective Cohort Study

Functional neurological disorder (FND) is a common and disabling condition with diverse presentations, such as motor (weakness, tremor, dystonia, gait), sensory, cognitive, and seizure-like symptoms, often in combination. 1 It is understood as a disorder of brain network dysfunction, in which the brain generates overly strong predictions about body states that override incoming sensory and motor signals, and symptoms arise from this mismatch. 2 Historically, FND has been conceptualised in terms of psychological stress or traumatic experiences, often arising in childhood. 3 However, contemporary models situate it within a broader biopsychosocial framework, in which early-life biological influences are poorly characterised compared to psychosocial factors. Previously reported inherited and neurodevelopmental associations with FND include Ehlers–Danlos syndrome and hypermobility spectrum disorders, 4 autism spectrum disorder, 5 and ADHD. 6 FND may be more likely to emerge in individuals with less reliable bodily signalling and regulatory systems, which may become apparent in the context of co-existing disease (e.g., FND emerging in Parkinson’s disease). 7 Similarly, disturbances of motor, sensory, or integrative processing earlier in life could predispose to FND. The authors compared the prevalence of early-life biological vulnerability factors in FND against comparator cohorts, and examined whether distinct vulnerability profiles are associated with specific FND phenotypes.