Cortisol and α-amylase awakening response in children and adolescents with functional neurological (conversion) disorder

Objective: Stress system dysregulation is considered to have an important role in the aetiology of paediatric functional neurological (conversion) disorder. This study examined salivary cortisol and α-amylase awakening responses in children with functional neurological disorder to determine activation patterns of the hypothalamic-pituitary-adrenal axis and sympathetic system. A healthy cortisol awakening response involves a robust increase in cortisol within 30 minutes of awakening. Alpha-amylase awakening response is variable in children.

Methods: Cortisol and α-amylase were measured in saliva from 32 patients with functional neurological disorder (26 girls and 6 boys, aged 11.3-16.1 years) and 31 healthy controls (23 girls and 8 boys, aged 8.6-17.7 years). Saliva samples were collected using a Salivette sampling device at two time points - upon awakening and 30 minutes after awakening.

Results: Patients with functional neurological disorder showed a decrease in cortisol awakening response (-4 nmol.min/L) and controls showed an increase (107 nmol.min/L), t(55) = -.4.6, p < 0.001. Within the functional neurological disorder group, 57% showed an attenuated cortisol awakening response and 43% showed an obliterated/reversed cortisol awakening response: Cortisol awakening response was negatively correlated with adverse childhood experiences, r(58) = -0.6, p = 0.002, and subjective distress (total Depression Anxiety and Stress Scales score), r(58) = -0.4, p = 0.050. In controls, cortisol awakening response showed no correlation with adverse childhood experiences and a positive correlation with subjective distress, r(56) = 0.4, p = 0.023. Total cortisol remained similar between the functional neurological disorder and control group. No significant differences were observed between the functional neurological disorder and control group in any of the α-amylase analyses.

Discussion: The results suggest dysregulation of the hypothalamic-pituitary-adrenal axis in children with functional neurological disorder. Hypothalamic-pituitary-adrenal dysregulation in children with functional neurological disorder may contribute to comorbid symptoms of fatigue, sleep disturbance and subjective loss of well-being because circadian rhythms and energy metabolism are disrupted. Hypothalamic-pituitary-adrenal dysregulation - and changes in glucocorticoid (cortisol) signalling at the molecular level - may also contribute to increased vulnerability for functional neurological disorder symptoms because of epigenetically mediated changes to neural networks implicated in functional neurological disorder.