Periodic Reporting for period 1 - ETHEREAL (EPIGENETIC-GENETIC-MENTAL HEALTH CASCADE BASED PERSONALISED PREVENTION OF NON-COMMUNICABLE DISEASE IN ADOLESCENTS DIAGNOSED WITH AUTISM (ETHEREAL))
Reporting period: 2023-01-01 to 2024-06-30
Recent research identified mental health disorders (MHD) as the highest ranked non communicable diseases (NCD) in adolescent population; a specific group in this population that is 3 - 6 times more vulnerable for developing MHD is represented by the adolescents diagnosed with Autism Spectrum Disorders (ASD). There is no Evidence Based Intervention (EBI) for preventing MHD in an ASD adolescent since: 1) the major risk factors are in-grained in their biological process and 2) they present with multiple MHD comorbidity.
Personalization is the key to prevent their already vulnerable mental states making transition to an MHD. Currently- "which" EBI is appropriate for "which" ASD adolescent and "how" to choose it represent unsolved questions. Recent research showed how the environmental factors can alter gene expressions that leads to an MHD through Epigenetic-Genetic/ metabolomic-Mental health (EGM) process.
By quantitatively modeling this process in a person-centric approach, ETHEREAL intends to design an ecosystem that prevents MHD and subsequently other NCDs in adolescents with ASD a. by empowering them to self-control their personal environmental risk factors whilst, b. facilitating the access to proper and personalized evidence-based interventions (EBIs) in their personal natural environment (PNE); c, improving in such way their QoL and independent living.
This will be done through following four main activities:
1. Identification of the environmental factors in the PNE of an adolescent with ASD which instigate transition of their already vulnerable “mental health” to MHD (ETHEREAL Model 1);
2. Quantitative modelling of the EGM process chain and design of control strategies (Model 2);
3. Integration of the Models 1 and 2 in a Personalized Digital Nurse (PDN) mobile app, that will empower adolescents with ASD to self-control the epigenetic influence of the factors present in their PNE;
4. Design of a personalized service delivery model that links the adolescent with the community care services (Model 3) and provides a set of formal neurobiologically informed selection criteria of the most appropriate adolescent-centric EBIs and will define methods for a rapid adoption pathway for the ETHEREAL system in day-to-day clinical practice
The project includes a 2-Part observational study:
• Part-I will generate heterogeneous neurophysiological, genetic, epigenetic, cognitive, and behavioural data that will be used in the modelling activity.
• Part-II will generate data to evaluate the outcomes of traditional EBIs when they are personalized based on the ETHEREAL models .
Personalization is the key to prevent their already vulnerable mental states making transition to an MHD. Currently- "which" EBI is appropriate for "which" ASD adolescent and "how" to choose it represent unsolved questions. Recent research showed how the environmental factors can alter gene expressions that leads to an MHD through Epigenetic-Genetic/ metabolomic-Mental health (EGM) process.
By quantitatively modeling this process in a person-centric approach, ETHEREAL intends to design an ecosystem that prevents MHD and subsequently other NCDs in adolescents with ASD a. by empowering them to self-control their personal environmental risk factors whilst, b. facilitating the access to proper and personalized evidence-based interventions (EBIs) in their personal natural environment (PNE); c, improving in such way their QoL and independent living.
This will be done through following four main activities:
1. Identification of the environmental factors in the PNE of an adolescent with ASD which instigate transition of their already vulnerable “mental health” to MHD (ETHEREAL Model 1);
2. Quantitative modelling of the EGM process chain and design of control strategies (Model 2);
3. Integration of the Models 1 and 2 in a Personalized Digital Nurse (PDN) mobile app, that will empower adolescents with ASD to self-control the epigenetic influence of the factors present in their PNE;
4. Design of a personalized service delivery model that links the adolescent with the community care services (Model 3) and provides a set of formal neurobiologically informed selection criteria of the most appropriate adolescent-centric EBIs and will define methods for a rapid adoption pathway for the ETHEREAL system in day-to-day clinical practice
The project includes a 2-Part observational study:
• Part-I will generate heterogeneous neurophysiological, genetic, epigenetic, cognitive, and behavioural data that will be used in the modelling activity.
• Part-II will generate data to evaluate the outcomes of traditional EBIs when they are personalized based on the ETHEREAL models .
The activities of the P1 Period (M1-M18) were devoted mainly: a.to build a technological platform suitable to collect multimodal data for the design of the ETHEREAL models through an observational study involving 400 adolescents with ASD; b.to realize the preparatory activities for the above mentioned clinical study at the 3 sites of Bucharest , Cork and Southampton.
Technical activities
We defined the architecture of the ETHEREAL system; it includes two main subsystems: a.the Home Monitoring Technology Platform (HMTP); b.the Clinical Server Platform (CSP) with the Central Repository (CR).
In the HMTP the core component is the Patient Digital Nurse (PDN) app where in the second part of the project (Period P2) the ETHEREAL Model 1 and Model 2 will be integrated.
In the P1 period the ETHEREAL system was designed mainly for the collection of data of the adolescent in his / her PNE and at clinic; at home wearable sensors and questionnaires will be used while medical data will be obtained through the periodic visits at clinic of the adolescents.
In the HMTP two apps were developed and tested for use both in Android- and iOS-based systems: 1. the ENIGMA app that allows the management of the questionnaires proposed to the adolescents and their parents and the provision of PNE data that is transferred to the Central Repository; 2. the VisionTool app that automatically pulls out the physiological signals from the sensors worn by the adolescents (raw data) and sends them to the middleware of the Clinical Server Platform for processing and feature extraction.
The developed CSP is composed by the Central Repository (CR) and a Middleware that - before the transfer to the CR - curates and processes the raw data coming from the wearable sensors and extracts the essential features such as, HRV and RR from ECG, and posture and total physical activity from accelerometer data.
The ETHEREAL system was designed through iterative development / testing / refinement cycles and by involving the main stakeholders (adolescents and their parents, medical professionals, technicians, educators and carers).
As result of this approach (including a pre-pilot at the three clinical sites) some functional shortcomings were identified and corrected.
Preparatory activities for the clinical studies
The activities included: a. the preparation and finalization of the clinical protocol; b.the approval by the Ethics Committees of the three clinical sites; c.the definition of the Data Protection Impact Assessment (DPIA) and its approval by the Data Protection Offices;
d.the recruitment of the adolescents participating to the clinical studies on the basis of the agreed exclusion and inclusion criteria.
Unfortunately – due to various reasons – at the end of the P1 Period (month M18) this preparatory phase is not yet completed and the recruitment phase has been started slowly and not in all the three clinical sites.
To cope with the accumulated delay, the Consortium defined a set of corrective actions and the Partners are confident that the project will be back on track and that its objectives will be achieved.
Technical activities
We defined the architecture of the ETHEREAL system; it includes two main subsystems: a.the Home Monitoring Technology Platform (HMTP); b.the Clinical Server Platform (CSP) with the Central Repository (CR).
In the HMTP the core component is the Patient Digital Nurse (PDN) app where in the second part of the project (Period P2) the ETHEREAL Model 1 and Model 2 will be integrated.
In the P1 period the ETHEREAL system was designed mainly for the collection of data of the adolescent in his / her PNE and at clinic; at home wearable sensors and questionnaires will be used while medical data will be obtained through the periodic visits at clinic of the adolescents.
In the HMTP two apps were developed and tested for use both in Android- and iOS-based systems: 1. the ENIGMA app that allows the management of the questionnaires proposed to the adolescents and their parents and the provision of PNE data that is transferred to the Central Repository; 2. the VisionTool app that automatically pulls out the physiological signals from the sensors worn by the adolescents (raw data) and sends them to the middleware of the Clinical Server Platform for processing and feature extraction.
The developed CSP is composed by the Central Repository (CR) and a Middleware that - before the transfer to the CR - curates and processes the raw data coming from the wearable sensors and extracts the essential features such as, HRV and RR from ECG, and posture and total physical activity from accelerometer data.
The ETHEREAL system was designed through iterative development / testing / refinement cycles and by involving the main stakeholders (adolescents and their parents, medical professionals, technicians, educators and carers).
As result of this approach (including a pre-pilot at the three clinical sites) some functional shortcomings were identified and corrected.
Preparatory activities for the clinical studies
The activities included: a. the preparation and finalization of the clinical protocol; b.the approval by the Ethics Committees of the three clinical sites; c.the definition of the Data Protection Impact Assessment (DPIA) and its approval by the Data Protection Offices;
d.the recruitment of the adolescents participating to the clinical studies on the basis of the agreed exclusion and inclusion criteria.
Unfortunately – due to various reasons – at the end of the P1 Period (month M18) this preparatory phase is not yet completed and the recruitment phase has been started slowly and not in all the three clinical sites.
To cope with the accumulated delay, the Consortium defined a set of corrective actions and the Partners are confident that the project will be back on track and that its objectives will be achieved.
Modelling the EGM cascades will provide clear guidance and the ETHEREAL project will push the frontiers of a holistic care system for preventing MHD in the context of ASD in different areas:
o Neurological modelling of epigenetic-genetic/metabolomic-mental health interaction that represents the missing link for personalization; it can be used in clinical practice for an effective and personalized management of mental health in adolescents.
o Prevention of MHD in ASD adolescents: ETHEREAL, for the first time, will identify the precise environmental markers based on underpinning environment neurological interaction process. Such “causal” marker identification will allow strategizing effective intervention to prevent that existing mental vulnerability in adolescents diagnosed with ASD escalates into MHD.
o Neurological modelling of epigenetic-genetic/metabolomic-mental health interaction that represents the missing link for personalization; it can be used in clinical practice for an effective and personalized management of mental health in adolescents.
o Prevention of MHD in ASD adolescents: ETHEREAL, for the first time, will identify the precise environmental markers based on underpinning environment neurological interaction process. Such “causal” marker identification will allow strategizing effective intervention to prevent that existing mental vulnerability in adolescents diagnosed with ASD escalates into MHD.