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      Pharmacogenomics and non-genetic factors affecting drug response in autism spectrum disorder in Thai and other populations: current evidence and future implications


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          Autism spectrum disorder (ASD) may affect family and social life profoundly. Although there is no selective pharmacotherapy for ASD, the Food and Drug Administration (FDA) has recommended risperidone/aripiprazole to treat the associated symptoms of ASD, such as agitation/irritability. Strong associations of some pharmacokinetic/pharmacodynamic gene variants, e.g., CYP2D6 and DRD2, with risperidone-induced hyperprolactinemia have been found in children with ASD, but such strong genetic associations have not been found directly for aripiprazole in ASD. In addition to pharmacogenomic (PGx) factors, drug–drug interactions (DDIs) and possibly cumulative effects of DDIs and PGx may affect the safety or effectiveness of risperidone/aripiprazole, which should be assessed in future clinical studies in children with ASD. Reimbursement, knowledge, and education of healthcare professionals are the key obstacles preventing the successful implementation of ASD pharmacogenomics into routine clinical practice. The preparation of national and international PGx-based dosing guidelines for risperidone/aripiprazole based on robust evidence may advance precision medicine for ASD.

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          A new initiative on precision medicine.

          President Obama has announced a research initiative that aims to accelerate progress toward a new era of precision medicine, with a near-term focus on cancers and a longer-term aim to generate knowledge applicable to the whole range of health and disease.
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            Autism spectrum disorder

            Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory–motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.
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              Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample.

              Autism spectrum disorders are now recognized to occur in up to 1% of the population and to be a major public health concern because of their early onset, lifelong persistence, and high levels of associated impairment. Little is known about the associated psychiatric disorders that may contribute to impairment. We identify the rates and type of psychiatric comorbidity associated with ASDs and explore the associations with variables identified as risk factors for child psychiatric disorders. A subgroup of 112 ten- to 14-year old children from a population-derived cohort was assessed for other child psychiatric disorders (3 months' prevalence) through parent interview using the Child and Adolescent Psychiatric Assessment. DSM-IV diagnoses for childhood anxiety disorders, depressive disorders, oppositional defiant and conduct disorders, attention-deficit/hyperactivity disorder, tic disorders, trichotillomania, enuresis, and encopresis were identified. Seventy percent of participants had at least one comorbid disorder and 41% had two or more. The most common diagnoses were social anxiety disorder (29.2%, 95% confidence interval [CI)] 13.2-45.1), attention-deficit/hyperactivity disorder (28.2%, 95% CI 13.3-43.0), and oppositional defiant disorder (28.1%, 95% CI 13.9-42.2). Of those with attention-deficit/hyperactivity disorder, 84% received a second comorbid diagnosis. There were few associations between putative risk factors and psychiatric disorder. Psychiatric disorders are common and frequently multiple in children with autism spectrum disorders. They may provide targets for intervention and should be routinely evaluated in the clinical assessment of this group.

                Author and article information

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                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                05 February 2024
                : 14
                : 1285967
                [1] 1 Department of Pharmacy , University of Rajshahi , Rajshahi, Bangladesh
                [2] 2 Division of Pharmacogenomics and Personalized Medicine , Department of Pathology , Faculty of Medicine Ramathibodi Hospital , Mahidol University , Bangkok, Thailand
                [3] 3 Laboratory for Pharmacogenomics , Ramathibodi Hospital , Somdech Phra Debaratana Medical Center SDMC , Bangkok, Thailand
                [4] 4 Department of Clinical Chemistry , Faculty of Allied Health Sciences , Chulalongkorn University , Bangkok, Thailand
                [5] 5 Cardiovascular Precision Medicine Research Group , Special Task Force of Activating Research (STAR) , Chulalongkorn University , Bangkok, Thailand
                [6] 6 Pharmacogenomics and Precision Medicine Clinic , Bumrungrad Genomic Medicine Institute (BGMI) , Bumrungrad International Hospital , Bangkok, Thailand
                [7] 7 Faculty of Pharmaceutical Sciences , Burapha University , Mueang, Thailand
                [8] 8 Department of Pharmacology and Therapeutics , MRC Centre for Drug Safety Science , Institute of Systems, Molecular, and Integrative Biology , University of Liverpool , Liverpool, United Kingdom
                Author notes

                Edited by: Oriana Awwad, The University of Jordan, Jordan

                Reviewed by: Akila Prashant, JSS Academy of Higher Education and Research, India

                Yazun Jarrar, Al-Balqa Applied University, Jordan

                *Correspondence: Chonlaphat Sukasem, chonlaphat.suk@ 123456mahidol.ac.th
                [ † ]

                These authors have contributed equally to this work

                Copyright © 2024 Biswas, Vanwong and Sukasem.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 30 August 2023
                : 26 December 2023
                The authors declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the 1) Mahidol University International Postdoctoral Fellowship, Mahidol University; 2) Faculty of Medicine, Ramathibodi Hospital, Mahidol University; and 3) Ratchadapisek Somphot Fund, Chulalongkorn University.
                Custom metadata
                Pharmacogenetics and Pharmacogenomics

                Pharmacology & Pharmaceutical medicine
                autism spectrum disorder,risperidone,aripiprazole,pharmacokinetic/pharmacodynamic,genetic polymorphisms,pharmacogenomics,precision medicine


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