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

Abstract

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.

Altered resting-state neural networks in children and adolescents with functional neurological disorder

“…Considered together, these data hint at complex biological processes involving the stress system (including the autonomic system and HPA axis) that may allow adverse life experiences to be biologically embedded and come to be expressed in altered neural network connectivity patterns. Potential pathways have been discussed elsewhere ( Chung et al, 2022 , Diez et al, 2021 , Agorastos et al, 2019 , McEwen et al, 2015 ).…”

“…A proportion of participants (18 FND, 20 controls) participated in a parallel study examining their CAR—using salivary cortisol—a marker of hypothalamic–pituitaryadrenal (HPA) axis function ( Chung et al, 2022 ).…”

“…It would have been helpful to examine whether this coupling was also present in the current study. A third limitation (difficulty) is the complexity of disentangling the complex, nonlinear biological pathways that are hypothesized to underpin FND and other stress-related disorders ( Chung et al, 2022 , Diez et al, 2021 , Agorastos et al, 2019 , McEwen et al, 2015 ). It is challenging to elucidate the contribution of multiple interacting factors—stage of development, biological embedding of experience, comorbidities, medication effects, and so on—and the biological pathways by which all these factors contribute to the picture.…”

“…They showed more variable reaction times, more false alarms, and more total errors on a cognitive task (the go/no-go test), and faster response times, while matching controls in accuracy, on an emotion-processing task (identification of emotion faces). A study examining cortisol awakening response (CAR)—using salivary cortisol—showed that this response was attenuated or reversed and that the degree of dysregulation correlated with the number of adverse childhood experiences (ACEs) and subjective distress ( Chung et al, 2022 ). These findings suggest that the neural underpinnings of FND may extend across motor-sensory, arousal-processing, emotion-processing, and cognitive-processing systems.…”

The biopsychosocial model in paediatric clinical practice—An interdisciplinary approach to somatic symptom disorders

“…[14][15][16] A recent study suggests a dysregulation of the hypothalamicpituitary-adrenal axis in children with functional neurological disorders. 16 One assumes that biological and genetic factors pose a risk of developing paediatric SSD; as there is found a clustering of SSD in families. 17 Furthermore, one suggests a shared, enhanced biological inclination to experience physical symptoms in a certain way between parent and child.…”