New publication from Prof. Santosh & team at CIPP Rett Centre

In April, a paper entitled, 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 by the CIPP Rett Centre in London headed by Professor Santosh.

Here, Rachael  Stevenson, CEO at Reverse Rett, attempts to better understand the paper in a Q and A format with one of the authors and Reverse Rett Research Review Committee member, Dr Jatinder Singh.

Please scroll to the end of the article if you want to read a more basic explanation of this work.

RES: What were you aiming to find out in this paper?

JS: Emotional, Behavioural and Autonomic Dysregulation (EBAD) frequently occurs in neurodevelopmental disorders. In patients with Rett Syndrome (RTT), there is limited information on how the autonomic components of EBAD can be targeted using different treatments and the impact of these treatments on the management of EBAD. As Rett patients have very limited communication skills, finding ways to assess EBAD symptoms remains challenging.

In this study, we wanted to see if we could treat the autonomic dysregulation in Rett patients by measuring Heart Rate Variability (HRV) and Electrodermal Activity (EDA) and assess the impact of treatment on the emotional and behavioural components of EBAD. We did this by (I) using wearable sensors to measure EDA and HRV in 10 Rett patients and (2) using different treatments to manage the EBAD symptoms.

RES: What did you find out?

JS: In this pilot study, we showed that in some patients, Buspirone could normalise EDA, and in another patient, an increase in EDA was associated with a worsening of emotional and behavioural symptoms. While HRV did not show clinically meaningful information in this patient group, EDA normalisation appears to be associated with improving EBAD symptoms in patients treated with Buspirone. This suggests that EDA would be helpful for monitoring autonomic dysregulation and provides a useful biomarker for tracking the symptoms of EBAD in Rett patients.

RES: Explain what ‘electrodermal’ activity is in the context of downstream responses of the autonomic system?

JS: The autonomic component of EBAD can be targeted, which can help manage the emotional and behavioural symptoms. Autonomic dysregulation occurs due to the imbalance of the Autonomic Nervous System (ANS). The ANS has two major components – the parasympathetic and sympathetic component that are tightly regulated.

In Rett patients, there is a problem in the way these components act, and like a see-saw, this balance can either shift to a more dominant parasympathetic or sympathetic profile. You may be asking, where does ‘electrodermal’ activity (EDA) fit into this? EDA reflects the electrical changes at the skin surface during sweating, which is regulated by sympathetic activity. Putting it simply, EDA is a measure of the sympathetic activity of the ANS, and this activity can be modulated by the environment (thermoregulation) or by the ANS (emotional or behavioural regulation).

RES: Why do you think heart rate variability is not as helpful in measuring baseline/clinical outcomes in Rett compared to EDA?

JS: Measurement of autonomic dysregulation is complex. This complexity is increased due to the different clinical presentations of EBAD across the Rett population. As the disorder advances, the symptoms of EBAD probably become worse. Other studies have shown HRV variability changes across the lifespan in Rett patients. The worsening of EBAD in Rett patients could be reflected by changes in HRV during different developmental milestones. In this pilot study, EDA seems to be a better indicator of the sympathetic component of the ANS. In our sample of 10 patients, HRV was highly variable and less associated with the symptomatic improvement in EBAD.

RES: Which symptoms did you see improving and is this clinically correlated with improved EDA baseline data with patients on Buspirone and Sertraline?

JS: In our sample, four patients were on buspirone, two on sertraline, one on gabapentin and three were not started on medications. In three patients, buspirone normalized the EDA, and this was reflected by an improvement in EBAD. The emotional and behavioural symptoms of both patients treated with sertraline (including one with normal EDA) also significantly improved.

RES: How could assessment of EDA through non-invasive wearable technology in Rett help manage complex patients who are treatment-resistant?

JS: Patients with EBAD typically can be treatment-resistant. Our study showed an association between buspirone treatment of EBAD in RTT patients and improved clinical symptoms. This was reflected by EDA values becoming normal.

The assessment of EDA using non-invasive wearable sensors could offer another cost-effective option for healthcare professionals to assess autonomic dysregulation in Rett patients objectively. This strategy could also pave the way for more individualised treatment options to manage EBAD in patients with complex symptoms who are also treatment-resistant.

RES: What are the key take-home messages for families?

JS: The key take-home message would be that elevated and sustained EDA levels can be a sign of impending or concurrent serious physical illness in patients with RTT. EDA could also provide valuable information concerning the physical deterioration of the patient by assessing how patients might adapt to autonomic changes in the longer term. All of this information can enrich guidance for families and may help keep people with Rett Syndrome of any age as safe as possible than they would be otherwise.

In short:

• People with Rett Syndrome often have emotional, behavioural and autonomic problems but we don’t have a lot of information about how to treat these problems in these particular patients. 

• It is also hard to know what is working to help these problems in people who aren’t able to speak or communicate in the usual way. 

• In this study, the Researchers looked at signs in the body which could be measured by wearable technology (like a Fit Bit), as they tried two different medications to try to treat EBAD issues in children with Rett Syndrome. 

• They found that measuring something called Electrodermal activity was helpful.  

• Electrodermal activity is connected to changes at the surface of our skin during sweating which can be a physical sign of having EBAD issues. 

• In some patients, Busipirone normalised EDA and the patients showed improvements in their EBAD symptoms. 

• Patients treated with Sertraline also showed significantly improved EDA. 

• One patient treated showed significant increase in her EDA which was later shown to be related to a period of severe illness within 48 hours.  

• The key message is that high EDA levels on an ongoing basis can be a sign of serious illness in patients with Rett. EDA could also provide information about improvements and deterioration in patients when trialling new medications for EBAD. 

The published manuscript can be found here.

Gualniera L, Singh J, Fiori F, Santosh P. Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome – EDA and HRV monitoring using wearable sensor technology. Journal of Psychiatric Research. 2021 Apr 7;138:186-193.

Definitions

Electrodermal Activity (EDA): refers to variations in  the electrical conductance at the skin surface in response to sweating

Heart Rate Variability (HRV): the variation of time between each heartbeat