82c4e5ce2e61ed575d3f29d1e5df64b7 290517.pdf 659b9c615054e38e98823bde2917d31aafb97535 290517.pdf 05e6313dd9293eafe335d658af7edfb0357f86a0bf940050720c4660f3b7ef96 290517.pdf Title: Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers Subject: 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. Keywords: ASD; pharmacogenetic intervention; pharmacotherapy; personalisation of treatment; antipsychotics; antidepressants; anxiolytics Author: Maria J. Arranz, Juliana Salazar, Valentin Bote, Alicia Artigas-Baleri, Alexandre Serra-LLovich, Emma Triviño, Jordi Roige, Carlos Lombardia, Martha Cancino, Marta Hernandez, Marc Cendros, Enric Duran-Tauleria, Natalia Maraver and Amaia Hervas Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Tue May 10 04:04:51 2022 CEST ModDate: Tue May 10 04:17:56 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1197865 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YFNERV+VnURWPalladioL Type 1 Custom yes yes no 10 0 UBMUBB+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 ECCGLX+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 VRLXFX+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 TWBWZR+CMSY10 Type 1 Builtin yes yes no 28 0 IAFAOG+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 92 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 96 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 100 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 104 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 111 0 BCDJEE+Calibri TrueType WinAnsi yes yes no 118 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 126 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 130 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 134 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 138 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 145 0 BCDJEE+Calibri TrueType WinAnsi yes yes no 152 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 164 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 168 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 172 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 176 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 183 0 BCDJEE+Calibri TrueType WinAnsi yes yes no 190 0 JLZORU+EURM10 Type 1 Builtin yes yes no 197 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-04-10 02:43:05 CEST RepresentationInformation: 290517.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-09 13:45:14 CEST Size: 1197865 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 333 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Cohort Destination: subsection.2.1 Item: Title: Pharmacogenetic Intervention Destination: subsection.2.2 Item: Title: Clinical Assessment of Response Destination: subsection.2.3 Item: Title: Statistical Analyses Destination: subsection.2.4 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.4 Info: Title: Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers Author: Maria J. Arranz, Juliana Salazar, Valentin Bote, Alicia Artigas-Baleri, Alexandre Serra-LLovich, Emma Triviño, Jordi Roige, Carlos Lombardia, Martha Cancino, Marta Hernandez, Marc Cendros, Enric Duran-Tauleria, Natalia Maraver and Amaia Hervas Subject: 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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