Transdiagnostic Dimensional Profiling of Neurodevelopmental Disorders

Overview

In recent years, the growing awareness of the multifactorial nature of neurodevelopmental disorders has stimulated interest in transdiagnostic approaches aimed at investigating underlying etiological mechanisms beyond traditional diagnostic categories. In this context, the present study seeks to provide a transdiagnostic profiling of both domain-general cognitive functions (attention, working memory, executive control) and domain-specific functions (phonological awareness, rapid naming, vocabulary, reading) underlying the main neurodevelopmental disorders in a large sample of preschool and school-age children (3-11 years), through the use of CRAB (Computerized Reading-related Assessment Battery). CRAB is a digital platform specifically developed by SUPSI and the Université de Genève to integrate, within a single testing environment, the assessment of the main domain-general and domain-specific cognitive functions underlying neurodevelopmental disorders. In particular, participating families will receive an email containing a link to access the CRAB platform, which will not include their personal data but rather a code provided by the staff of IRCCS Medea. A screen will open displaying several game-like tasks designed to measure both domain-general and domain-specific cognitive functions, which must be completed by the participating subject. The main objective is to obtain a fine-grained and multidimensional mapping of cognitive profiles prior to the standard diagnostic process, in order to identify early patterns of (a)typical or at-risk functioning.

Background:In recent years, the growing awareness of the multifactorial nature of neurodevelopmental disorders has stimulated interest in transdiagnostic approaches aimed at investigating underlying etiological mechanisms beyond traditional diagnostic categories. Dimensional models proposed within cognitive psychology and developmental neuroscience suggest that the difficulties underlying different neurodevelopmental disorders arise from the interaction of multiple cognitive, linguistic, and executive factors, rather than from isolated deficits. However, in clinical and educational practice, the assessment of these functions often remains fragmented, heterogeneous, and dependent on clinical judgment. Within this context, the present study aims to provide a transdiagnostic profiling of a large sample of preschool and school-age children (3-11 years) through CRAB (Computerized Reading-related Assessment Battery). CRAB is a digital platform developed by the Université de Genève and SUPSI, specifically designed to integrate within a single testing environment the main domain-general cognitive functions (attention, working memory, executive control) and domain-specific functions (phonological awareness, rapid naming, vocabulary, reading) underlying neurodevelopmental disorders. The main objective is to obtain a fine-grained and multidimensional mapping of cognitive profiles prior to the standard diagnostic process, in order to identify early patterns of (a)typical or at-risk functioning. The digital nature of CRAB allows for standardized, ecologically valid, and scalable administration, reducing barriers related to the availability of expert evaluators and the logistical limitations of traditional assessments. Moreover, the platform incorporates elements of gamification and a structured onboarding process to ensure engagement and task comprehension even among younger children-an aspect that is crucial for the quality of the collected data. Adopting a transdiagnostic approach makes it possible to overcome the rigidity of categorical labels, promoting a dimensional and continuous view of the cognitive functions involved in the etiology of neurodevelopmental disorders. This perspective aligns with the most recent international frameworks (such as RDoC - Research Domain Criteria), which propose investigating neurodevelopmental disorders along shared functional dimensions. The data collected through CRAB will make it possible to explore interindividual variability in cognitive developmental trajectories and to identify profiles of strengths and weaknesses that cut across different clinical conditions or performance levels. Primary objective: The primary objective of this project is to obtain a fine-grained and multidimensional profiling of domain-general and domain-specific cognitive functions underlying the main neurodevelopmental disorders, prior to the standard diagnostic process. Data collected through the CRAB platform will be analyzed in association with the clinical diagnosis issued at the end of the standard diagnostic pathway, in order to characterize cognitive profiles and transdiagnostic patterns of functioning. Secondary objective: The secondary objective of the study is to identify patterns of relationships between domain-general and domain-specific abilities that characterize different neurodevelopmental disorders (within-disorder and between-disorders). Finally, the data collected will allow for the evaluation of the usability of the CRAB digital platform in highly ecological contexts (home environment) using commonly available devices (tablets and computers). The primary outcome of the study consists of the multidimensional cognitive profiles obtained through the CRAB platform, administered prior to the start of the standard clinical diagnostic process. CRAB enables the integrated assessment of domain-general cognitive functions (attention, working memory, executive control) and domain-specific functions (phonological awareness, rapid naming, vocabulary, reading) underlying the main neurodevelopmental disorders. Primary outcomes: * Individual multidimensional cognitive profile, represented by the set of performances on the tasks included in CRAB; * Association between the CRAB cognitive profile and the final clinical diagnosis, issued independently of the project at the end of the diagnostic process at the Istituto Scientifico IRCCS Medea - Associazione "La Nostra Famiglia". Secondary outcomes: Identification of transdiagnostic cognitive clusters, based on CRAB domain scores standardized by age or within the space defined by principal components; Distribution of clinical diagnostic categories within the identified cognitive clusters; Evaluation of the usability and acceptability of the CRAB platform, through questionnaires administered to children/parents/clinicians, system indicators (logs, task completion, reports of difficulties), and standardized observations of administration quality; Feasibility of early digital screening, assessed through completion rates, data quality, technical robustness of the platform, and compliance with criteria for integration into clinical settings. Study design Prospective, observational, single-center, non-profit study. Study duration: 36 months (3 years) Estimated start date: May 4, 2026 The total study duration is estimated at 36 months and is structured as follows: * Months 1-6: revision, optimization, and piloting of the CRAB platform; * Months 7-30: main data collection; * Months 10-33: parallel data analysis. The study includes a single CRAB assessment session for each participant, lasting approximately 60 minutes, administered prior to the standard diagnostic pathway. The collected cognitive data will subsequently be analyzed in relation to the clinical diagnosis issued at the end of the diagnostic process, allowing for the description and comparison of multidimensional cognitive profiles from a transdiagnostic perspective. CRAB is a digital platform developed by the Université de Genève and SUPSI and made available to IRCCS Eugenio Medea through a non-exclusive, non-transferable license limited to the current project. The system enables standardized collection of domain-general and domain-specific cognitive functions and includes a structured onboarding process and gamified components to enhance comprehension and engagement in children. Setting The CRAB battery may be administered: * in a clinical setting, within spaces dedicated to neuropsychological assessment. Participants will be recruited from the Territorial Unit of Child and Adolescent Neuropsychiatry (NPIA) at IRCCS Eugenio Medea - Associazione "La Nostra Famiglia", Bosisio Parini (LC); * in a home environment, via remote access to the web-based CRAB platform. The recruitment period is planned between months 3 and 30 of the project, with an estimated sample of at least 300 children. CRAB assessment will take place before the clinical diagnosis, enabling the study of relationships between cognitive profiles and subsequent diagnostic classifications. Study population The study population consists of children referred for the first time to the Territorial Unit of Child and Adolescent Neuropsychiatry (NPIA) at IRCCS Eugenio Medea - Associazione "La Nostra Famiglia", Bosisio Parini (LC), for suspected neurodevelopmental or psychopathological disorders. The project will be proposed to all children aged 3 to 11 years (from the first year of preschool to the fifth year of primary school). This is a heterogeneous population reflecting the variety of profiles typically seen in neuropsychiatric services, including suspected neurodevelopmental disorders (e.g., reading disorders, ADHD, language disorders, developmental coordination disorder), learning difficulties, or other clinical concerns. The study does not involve interventions or group allocation, but only a single digital data collection via CRAB prior to the standard diagnostic process. Data sources include: * cognitive test performance collected via CRAB; * essential demographic information; * final clinical diagnosis provided by the NPIA team at the end of the diagnostic process. Inclusion criteria * Age between 3 and 11 years; * First access to the NPIA service at IRCCS Eugenio Medea (Bosisio Parini); * Suspected neurodevelopmental or psychopathological disorder; * Completion of the standard clinical diagnostic pathway; * Availability of a compatible device (tablet or computer) for remote administration, if applicable. Exclusion criteria * Age outside the specified range; * Failure to complete the diagnostic pathway; * Lack of access to a compatible device (for remote administration); * Severe sensory impairments (uncorrected blindness or deafness); * Motor impairments preventing use of digital devices; * Significant lack of understanding of the Italian language affecting task comprehension. Study outcomes The primary outcome consists of multidimensional cognitive profiles obtained via CRAB prior to the clinical diagnostic process. Primary outcomes: * Individual multidimensional cognitive profile based on CRAB task performance; * Association between CRAB cognitive profile and final clinical diagnosis. Secondary outcomes: Identification of transdiagnostic cognitive clusters; Distribution of clinical diagnoses across identified clusters; Usability and acceptability of CRAB (questionnaires, system logs, standardized observations); Feasibility of early digital screening. Variables * Quantitative domain-general and domain-specific cognitive variables (accuracy, response times, composite indices); * Clinical categorical variables (final diagnosis); * Demographic variables (age, sex) and socio-environmental variables (caregiver occupation, bilingualism); * Potential confounders (device familiarity, completion time, need for support); * Usability and data quality indicators (task completion rate, help requests, technical interruptions, usability scores). Bias Potential biases include measurement variability, confounding variables (e.g., age, bilingualism), and technical issues. Mitigation strategies include standardized digital administration, collection of confounders, multivariate statistical control, and quality monitoring systems. Sample size This is an exploratory study. Based on assumptions (α = 0.05, power = 80%, event probability = 0.3, OR = 1.5), the estimated sample size is 242 participants. The planned enrollment of approximately 300 participants ensures adequate statistical power. The calculation was performed using G\*Power. Recruitment procedure Participants will be recruited after first contact with the NPIA service and completion of MedicalBit questionnaires. Only children for whom a neuropsychiatrist recommends a diagnostic pathway will be enrolled. Follow-up: None planned. End of study: For each participant, the study ends at completion of the diagnostic process. The overall study ends after 36 months. Data collection and management Data are collected through CRAB, MedicalBit, and clinical records. Each participant is assigned a pseudonymized code generated by IRCCS Medea. Identifiable data are stored separately and not shared with research partners. CRAB data are securely stored on Université de Genève servers and transferred to REDCap. Access is restricted to authorized personnel. Data protection Data are processed in compliance with GDPR (EU 679/2016). Pseudonymization ensures separation between identity and research data. Only aggregated data will be used for publications. Statistical analysis plan * Descriptive statistics of cognitive scores; * Correlation analyses (Pearson/Spearman); * Age standardization of scores; * Principal Component Analysis (PCA) for dimensionality reduction; * Multinomial logistic regression to assess associations with diagnosis; * Cluster analysis to identify transdiagnostic profiles; * Descriptive analysis of usability and feasibility indicators; * Handling of missing data (exclusion or multiple imputation where appropriate); * Sensitivity analyses to assess robustness. Safety The study is observational and does not introduce additional risk. Minor discomfort (e.g., fatigue) will be managed by pausing or stopping the session. No medical adverse events are expected. Administrative aspects Funding: The study is funded by IRCCS Eugenio Medea through 5x1000 research funds. It is a non-profit study, and the funder has no role in the research. Ethical considerations The study will be conducted in accordance with the Declaration of Helsinki and applicable regulations. Approval from the relevant Ethics Committee has been requested. Informed consent and data processing As the study involves minors, written informed consent from parents or legal guardians is required. Clear study information is provided, and children receive age-appropriate explanations, with assent obtained when possible. All data are processed in compliance with European and national data protection regulations. Participants' identities are not shared with research partners, and linkage information is stored exclusively at IRCCS Eugenio Medea.