Combination of Predictive Biomarkers to Increase Diagnostics Efficiency of Autism Spectrum Disorder

Mind the Gap: a Bridge Between Research and Clinic for the Prevention and Diagnosis of Autism Spectrum Disorders

Early identification and diagnosis of autism spectrum disorder (ASD) is necessary to promote access to early treatment. Despite the high incidence, in Italy it is estimated that 1 in 77 children (age 7-9 years) (Narzisi et al., 2018), the diagnosis and the choice of rehabilitation treatment for patients with Autism Spectrum Disorder (ASD) are still based on clinical observation. In the absence of targeted pharmacological therapies, early surveillance and evaluation aimed at timely intervention represent the only successful strategy to reduce the severity of symptoms (Palomo R et al., 2006) and improve the quality of life of children affected by ASD and their families, thus also leading to a reduction in costs for the National Health Service (Ganz ML. 2007). However, compared to the great advances in neuroscience, the clinical management of autistic individuals is seriously lagging behind, and the disorder is often diagnosed after 3-4 years of age despite the presence of deficits starting from the very first months of life (Zwaigenbaum L et al. al., 2013). The aim of this project is to bridge the gap between research and clinic, thanks to the convergence of multiple biological and clinical data.

The purpose of this project is to combine multiple biological levels of information and their matching with the clinical phenotype and personal/family anamnesis of the single individual. In fact, by stratifying multiple levels of biomarkers, including behavioral (eye tracking), clinical and neuropsychological variables, parameters taken from transcriptomics (RNAseq), the goal is to identify a panel of intermediate biomarkers capable of (a) distinguishing autistic subjects from typically developing brothers/sisters, (b) to distinguish autistic subjects from typically developing subjects, (c) to stratify autistic patients into a limited number of homogeneous subgroups by physiopathology, in order to allow personalized pharmacology and improve their management clinic.

Autistic Spectrum Disorder patients, Inclusion Criteria:

• aged between 4 and 17years;
• Autism Spectrum Disorder diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria;
• healthy brothers/sisters, aged 4 to 17 years;
• adequate ocular vision, i.e. absence of objective eye problems such as double vision, cataracts, etc.;
• ability to maintain position in front of the monitor, i.e. knowing how to maintain or regain posture independently or with the help of postural aids;
• cognitive skills appropriate to the task such as being able to recognize images.

ASD siblings and Typical Developmental children, Inclusion Criteria

• aged between 4 and 17years;
• typical development, absence of known pathologies;
• adequate ocular vision, i.e. absence of objective eye problems such as double vision, cataracts, etc.;
• ability to maintain position in front of the monitor, i.e. knowing how to maintain or regain posture independently or with the help of postural aids;
• cognitive skills appropriate to the task such as being able to recognize images.

Autistic Spectrum Disorder patients, Exclusion Criteria:

• age not between 4 years and 17 years;
• difficulty in controlling ocular motility and visual hookup;
• unavailability of at least one sibling to participate in the diagnostic process;
• subjects with a syndromic phenotype or for which the presence of a known genetic syndrome has already been ascertained (e.g. Syndrome Rett, Xfra, Tuberous Sclerosis, etc.).

ASD siblings and Typical Developmental children, Exclusion Criteria:

• age not between 4 years and 17 years;
• subjects diagnosed with moderate/severe intellectual disability, or affected by known neurological pathologies (infantile cerebral palsy, epilepsy, sensory deficits) or with a history of preterm birth (≤32w) or underweight (≤10°ile for gestational age);
• subjects with a syndromic phenotype or for which the presence of a known genetic syndrome has already been ascertained (e.g. Syndrome Rett, Xfra, Tuberous Sclerosis, etc.);
• difficulty in controlling ocular motility and visual hookup;
• subjects suffering from neurodevelopmental disorders or family history for ASD for the control group.