BACKGROUND: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30–50% do not respond adequately and/or present severe and long-lasting side effects. METHODS: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24–48 h of receiving a biological sample. RESULTS: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: −0.87, SD 9.4, p = 1 × 10−5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10−8). CONCLUSIONS: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.

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Autistic spectrum disorders (ASD) children and adolescents usually present comorbidities, with 40-70% of them affected by attention deficit hyperactivity disorders (ADHD). The first option of pharmacological treatment for these patients is methylphenidate (MPH). ASD children present more side effects and poorer responses to MPH than ADHD children. The objective of our study is to identify genetic biomarkers of response to MPH in ASD children and adolescents to improve its efficacy and safety. Patients and Methods: A retrospective study with a total of 140 ASD children and adolescents on MPH treatment was included. Fifteen polymorphisms within genes coding for the MPH target NET1 (SLC6A2) and for its primary metabolic pathway (CES1) were genotyped. Multivariate analyses including response phenotypes (efficacy, side-effects, presence of somnolence, irritability, mood alterations, aggressivity, shutdown, other side-effects) were performed for every polymorphism and haplotype. Results: Single marker analyses considering gender, age, and dose as covariates showed association between CES1 variants and MPH-induced side effects (rs2244613-G (p=0.04), rs2302722-C (p=0.02), rs2307235-A (p=0.03), and rs8192950-T alleles (p=0.03)), and marginal association between the CES1 rs2302722-C allele and presence of somnolence (p=0.05) and the SLC6A2 rs36029-G allele and shutdown (p=0.05). A CES1 haplotype combination was associated with efficacy and side effects (p=0.02 and 0.03 respectively). SLC6A2 haplotype combination was associated with somnolence (p=0.05). Conclusion: CES1 genetic variants may influence the clinical outcome of MPH treatment in ASD comorbid with ADHD children and adolescents.

IntroductionThe ASD Day Therapeutic Unit of the HUMT is an interdisciplinary reference center specialized in ASD, for the care of children and adolescents with this pathology, that offers care by programs with the aim of achieving functionality altered.ObjectivesThe main objective of this study is to know the clinical characteristics of the patients admitted to our center and to offer preliminary data on the functional improvement achieved in a pilot program that works by processes.MethodsThis is a prospective clinical study of patients with ASD, treated at the ASD Day Therapeutic Unit of the Hospital Universitario Mutua Terrassa (HUMT), since februay 2022 till nowadays. We compare the clinical improvement and functionality acquired through the evaluation through various scales: Conners scale, SRS, BRIEF and CBCL.ResultsOur sample is made up of 19 patients with ASD who are admitted to the HUMT ASD Day Hospital. 13 belonged to the intensive care program, 5 to recovery of low-functioning functionality, and 1 to the differential diagnosis program. 84.21% (n=16) have preserved cognitive capacity. The median age is 13.1 years. 73.7% of the sample are men.We observed that 89% of patients admitted to our unit presented comorbid symptoms with ADHD. more than 78.9% present isolation, anxiety/depression, altered thinking and attention difficulties. 13/19 present a SEVERE RANGE of affectation upon admission, in social area. Facing discharge, the CBCL shows us a general improvement in behavior and comorbidity in the total scale. The SRS shows us an improvement in social awareness, social communication, social motivation, repetitive behavior and stereotypes and in the total score.ConclusionsSpecific interventions in social skills, autonomy, social understanding, daily routines, and sensory integration in patients with ASD improve core symptoms, as well as associated behavior.Specific interventions and working on social relationships during admission improve comorbidity derived from ASD.More studies are needed to specify the most efficient interventions to improve the quality of life in children and teenagers with ASD.Disclosure of InterestNone Declared