Skin conductance — the electrical activity on the surface of the skin in response to stimuli, as measured using wrist-worn devices — is indicative of changes in emotions and behaviors that affect the autonomic nervous system of Rett syndrome patients, a pilot study reports.

Together, these alternations are known as emotional behavioral and autonomic dysregulation (EBAD), and common across a wide range of neurodevelopmental disorders, study researchers noted.

EBAD can effectively be managed with appropriate medications, and specific measures captured via wearable devices help to monitor its symptoms, they added.

The study, “Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome – EDA and HRV monitoring using wearable sensor technology,” was published in the Journal of Psychiatric Research.  

Changes in the autonomic nervous system are common in people with Rett syndrome, leading to emotional, behavioral, respiratory, cardiac, and digestive impairments.  

Autonomic dysregulation refers to problems with the workings of the autonomic nervous system, which regulates involuntary functions such as heart rate, digestion, and respiratory rate.

It results from the underdevelopment of nerve networks, and causes an imbalance in the two components of the autonomic nervous system: sympathetic activity (sometimes called “fight-or-flight”), and a high-frequency component that corresponds with the parasympathetic response, or “rest-and-digest.”

As managing EBAD in Rett patients is limited by a lack of reliable measures and biomarkers, Researchers in the U.K. sought to characterize and monitor patients’ EBAD symptoms.

They used the Rett Evaluation of Symptoms and Treatment questionnaire from the HealthTracker online platform, and wearable sensor technology to measure heart rate variability — the variation in time between heartbeats — and electrodermal activity (EDA), which refers to small changes in the skin’s electrical activity.

A total of 10 Rett patients, ages 6 to 20 (mean age, 11.87), were recruited at the Centre for Personalised Medicine in Rett Syndrome at King’s College in London. 

All 10 had emotional symptoms, such as anxiety; all but one had evidence of autonomic dysregulation, including disordered breathing, cardiac problems, and gastrointestinal difficulties. Three had behavioral symptoms, including screaming episodes and hyperactivity. 

Among these patients, three were not being treated for EBAD symptoms, four were treated with buspirone (used in cases of anxiety), two with sertraline — used to treat depression, among other disorders — and one with the anticonvulsant gabapentin. 

The patients were assessed over four to 28 months, with an average follow-up time of 14.2 months.

During follow-up, treated and untreated patients showed favorable changes in heart rate variability metrics, while only treated patients showed such changes in EDA. 

“Most treated patients achieved a better management of their symptoms regardless of one or more abnormal HRV [heart rate variability] statistics detected,” the researchers wrote.

The study highlights two cases: a 14-year-old on buspirone for four months, who showed a pronounced reduction in anxiety, screaming episodes, and breathing difficulties, as well as normalized EDA values and heart rate frequency.

The other involved an 18-year-old on gabapentin for seven months, who required intensive care due to septicemia ( blood poisoning by bacteria). This patient showed a sustained EDA increase, rising to abnormal levels, without a clear worsening of emotional and behavioral symptoms.

“Very high and sustained EDA levels may be a biomarker for concurrent serious physical illness in RTT [Rett],” the researchers wrote. “Unlike the EDA, the analyses of [heart rate variability] metrics did not reveal patterns that were associated with clinical outcomes.” 

Among the study’s limitations, the scientists said, were its small sample size, the variable quality and reliability of heart rate readings, operator error in setting up the wrist-worn devices, and the use of an unfamiliar setting for assessments rather than a familiar environment such as the home.

“In this pilot study, we demonstrated that symptoms of EBAD can be effectively monitored using observational and autonomic measurements and managed with appropriate drug treatment,” the investigators  concluded.

“Moving forward, larger placebo-controlled studies are needed to investigate EDA changes in response to different medications, the effects of phenotypic [observable] variability on EDA and the relationship between this parameter and the severity of EBAD symptoms,” they added.

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