Review
Pharmacology & Pharmacy
Laura Perez-Cano, Sara Azidane Chenlo, Ruben Sabido-Vera, Francesco Sirci, Lynn Durham, Emre Guney
Summary: Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental disorders (NDDs) with a high medical need. The current behavior-based criteria used for diagnosing ASD overlooks the heterogeneity in clinical and genomic aspects, leading to failed clinical trials. This article highlights the urgent need to create a precision medicine framework for ASD and other NDDs, utilizing omics and systems biology to identify more homogeneous disease subtypes and develop tailored treatments. Recent initiatives towards precision medicine and cost-effective drug discovery for NDDs are also discussed.
DRUG DISCOVERY TODAY
(2023)
Article
Health Care Sciences & Services
Ghada Mubarak, Farah R. Zahir
Summary: With the rise of genome-wide screening methods, precision and personalized medicine have seen significant development. Transcriptomics and epitranscriptomics have emerged as important fields in defining disease causes and exploring therapeutic benefits. Advances in these fields have contributed to diagnostics and disease pathophysiological studies.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Psychiatry
Edgard Verdura, Laura Perez-Cano, Ruben Sabido-Vera, Emre Guney, Jean-Marc Hyvelin, Lynn Durham, Baltazar Gomez-Mancilla
Summary: Fragile X syndrome (FXS) is characterized by clinical, genetic, and therapeutic response heterogeneity, emphasizing the need for precision medicine-based treatments. The high genetic and phenotypic heterogeneity in FXS poses challenges in drug development. Precision medicine approaches, by accurately stratifying patients and defining drug responder profiles, have the potential to improve clinical trial success rates and benefit a larger number of patients with neurodevelopmental disorders.
FRONTIERS IN PSYCHIATRY
(2021)
Editorial Material
Neurosciences
Ana Kostic, Joseph D. Buxbaum
Summary: Autism spectrum disorder is a clinically and etiologically diverse developmental condition characterized by diminished social interactions, impaired communication, and repetitive and/or restrictive behaviors. Recent advances in ASD genetics open up opportunities for the implementation of precision medicine in the clinical management of autism.
Article
Behavioral Sciences
Rachel Goodson, Jennifer Wagner, Tracy Sandritter, Vincent S. Staggs, Sarah Soden, Cy Nadler
Summary: This study investigated the outcomes of pharmacogenetic testing in youth with ASD referred to a precision medicine clinic. The results showed high variability in medication response and no association between patient characteristics and pharmacogenomic testing results.
JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
(2023)
Review
Pharmacology & Pharmacy
George T. Chen, Daniel H. Geschwind
Summary: Neurodevelopmental Disorders (NDDs) encompass a wide range of disorders, including autism spectrum disorders (ASD) and schizophrenia (SCZ), which are linked to brain developmental processes. The clinical treatment of these disorders has traditionally focused on symptom management due to the variability in developmental disruption and limited knowledge of the underlying molecular mechanisms. With the identification of several hundred genes associated with ASD and SCZ, there is potential for new therapeutic approaches and the opportunity for precision medicine. This review discusses the progress in research technologies that enhance our understanding of disease progression and highlights advances in targeted clinical treatment and ongoing preclinical efforts in NDD precision medicine.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Medicine, General & Internal
Alina Kepka, Agnieszka Ochocinska, Sylwia Chojnowska, Malgorzata Borzym-Kluczyk, Ewa Skorupa, Malgorzata Knas, Napoleon Waszkiewicz
Summary: L-carnitine plays a vital role in the mitochondrial metabolism of fatty acids in the central nervous system and has been found to be altered in patients with autism spectrum disorder (ASD). Monitoring L-carnitine levels and acylcarnitine profiles can be useful in diagnosing and treating ASD. Supplementation of L-carnitine may help alleviate symptoms in ASD patients.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Health Care Sciences & Services
Catalina Mihaela Anastasescu, Veronica Gheorman, Florica Popescu, Eugen-Cristi Stoicanescu, Victor Gheorman, Anca-Lelia Riza, Oana Badea, Ioana Streata, Felicia Militaru, Ion Udristoiu
Summary: This study analyzed the serum amino acid profile in children diagnosed with autistic spectrum disorder (ASD) and found lower levels of taurine and higher levels of asparagine and leucine in the ASD group compared to the control group. Age also influenced the levels of tryptophan and alpha-aminobutyric acid.
Article
Neurosciences
Xiao-Hong Bao, Bao-Fu Chen, Jun Liu, Yu-Hua Tan, Shu Chen, Fan Zhang, Hong-Sheng Lu, Ji-Cheng Li
Summary: Due to the lack of valid biomarkers, the diagnosis of autism spectrum disorder (ASD) relies solely on behavioral phenotypes. This study aimed to identify novel circulating inflammatory biomarkers for ASD. Thirteen up-regulated proteins were found in the ASD group, and four proteins (STAMBP, ST1A1, SIRT2, and MMP-10) showed good diagnostic accuracy. These proteins may potentially serve as early diagnostic biomarkers for ASD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
James C. McPartland
Summary: This commentary discusses reasonable biomarker expectations in Autism Spectrum Disorder (ASD) by emphasizing the importance of defining clear objectives for biomarkers and evaluating them based on best practices.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Masud Rabbani, Munirul M. Haque, Dipranjan Das Dipal, Md Ishrak Islam Zarif, Anik Iqbal, Amy Schwichtenberg, Naveen Bansal, Tanjir Rashid Soron, Syed Ishtiaque Ahmed, Sheikh Iqbal Ahamed
Summary: This study aimed to evaluate the behavioral patterns of children with ASD during and after the COVID-19 lockdown, and found that support in the areas of problematic behavior could mitigate future risks.
SCIENTIFIC REPORTS
(2021)
Article
Biochemical Research Methods
Yan Wang, Jishui Zhang, Wenqi Song, Xiaoyi Tian, Ying Liu, Yanfei Wang, Jie Ma, Chengbin Wang, Guangtao Yan
Summary: This study analyzed and validated potential urinary biomarkers for ASD using mass spectrometry proteomics. A total of 34 significantly changed proteins were found in the discovery set, and seven proteins were identified as potential biomarkers for ASD through PRM assays. The results lay the groundwork for additional research on using biomarkers for the clinical diagnosis of ASD.
JOURNAL OF PROTEOMICS
(2021)
Article
Behavioral Sciences
Laura Turriziani, Arianna Ricciardello, Francesca Cucinotta, Fabiana Bellomo, Giada Turturo, Maria Boncoddo, Silvestro Mirabelli, Maria Luisa Scattoni, Maddalena Rossi, Antonio M. Persico
Summary: The study shows that gut mobilization significantly reduces symptoms such as hyperactivity, anxiety, irritability, and repetitive behaviors in chronically constipated autistic children. While urinary p-cresol levels varied, they were not significantly correlated with changes in behavioral parameters.
Article
Pediatrics
Benjamin Gesundheit, Philip David Zisman, Leah Hochbaum, Yehudit Posen, Avraham Steinberg, Gerald Friedman, Hersh D. Ravkin, Eitan Rubin, Ouriel Faktor, Ronald Ellis
Summary: The aim of this study was to identify diagnostic biomarkers for autism spectrum disorder (ASD) that could distinguish between ASD and typically developing children. By analyzing blood samples from 102 children with ASD and 97 typically developing children, 12 biomarkers were identified that achieved an accuracy of 82% in diagnosing ASD with a threshold of 0.5. These biomarkers have the potential to serve as an objective assay for early and accurate diagnosis of ASD.
FRONTIERS IN PEDIATRICS
(2023)
Article
Neurosciences
Bingbing Li, Yiran Xu, Dizhou Pang, Qiang Zhao, Lingling Zhang, Ming Li, Wenhua Li, Guiqin Duan, Changlian Zhu
Summary: Evidence suggests that dysregulation of homocysteine is associated with autism spectrum disorder (ASD). High levels of homocysteine are found in children with ASD compared to healthy controls, and homocysteine can be a diagnostic biomarker for ASD. Low levels of folate and vitamin B12 are also associated with poor clinical profiles in children with ASD.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Arjun Sethi, Suzanne O'Brien, James Blair, Essi Viding, Mitul Mehta, Christine Ecker, Nigel Blackwood, Moira Doolan, Marco Catani, Stephen Scott, Declan G. M. Murphy, Michael C. Craig
Summary: This study found that parenting interventions can reduce antisocial behavior in some children, but not in others. The study also identified abnormal brain activity as a significant factor associated with persistent antisocial behavior. The results suggest that addressing the underlying brain activity may be necessary to effectively treat behavior problems in children.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Iva Ilioska, Marianne Oldehinkel, Alberto Llera, Sidhant Chopra, Tristan Looden, Roselyne Chauvin, Daan Van Rooij, Dorothea L. Floris, Julian Tillmann, Carolin Moessnang, Tobias Banaschewski, Rosemary J. Holt, Eva Loth, Tony Charman, Declan G. M. Murphy, Christine Ecker, Maarten Mennes, Christian F. Beckmann, Alex Fornito, Jan K. Buitelaar
Summary: This study found a brainwide pattern of hypo- and hyperconnectivity in individuals with autism, primarily affecting sensory and higher-order attention networks, as well as the default mode network and subcortex. These connectivity alterations were stable and trait-like features of autism, independent of age and sex, and correlated with social difficulties, restrictive and repetitive behaviors, and alterations in sensory processing.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Psychiatry
Sarah Baumeister, Carolin Moessnang, Nico Bast, Sarah Hohmann, Pascal Aggensteiner, Anna Kaiser, Julian Tillmann, David Goyard, Tony Charman, Sara Ambrosino, Simon Baron-Cohen, Christian Beckmann, Sven Bolte, Thomas Bourgeron, Annika Rausch, Daisy Crawley, Flavio Dell'Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Dorothea L. Floris, Vincent Frouin, Hannah Hayward, Rosemary Holt, Mark H. Johnson, Emily J. H. Jones, Meng-Chuan Lai, Michael Lombardo, Luke Mason, Bethany Oakley, Marianne Oldehinkel, Antonio M. Persico, Antonia San Jose Caceres, Thomas Wolfers, Eva Loth, Declan G. M. Murphy, Jan K. Buitelaar, Heike Tost, Andreas Meyer-Lindenberg, Tobias Banaschewski, Daniel Brandeis
Summary: This study aimed to assess reward processing in individuals with autism spectrum disorder (ASD) in response to social and monetary rewards. The results showed that individuals with ASD exhibited hypoactivation in the right ventral striatum during reward anticipation compared to typically developing participants. However, there was no significant hyperactivation during the delivery of rewards. These findings do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing.
BRITISH JOURNAL OF PSYCHIATRY
(2023)
Article
Psychiatry
Viola Hollestein, Geert Poelmans, Natalie J. Forde, Christian F. Beckmann, Christine Ecker, Caroline Mann, Tim Schaefer, Carolin Moessnang, Sarah Baumeister, Tobias Banaschewski, Thomas Bourgeron, Eva Loth, Flavio Dell'Acqua, Declan G. M. Murphy, Nicolaas A. Puts, Julian Tillmann, Tony Charman, Emily J. H. Jones, Luke Mason, Sara Ambrosino, Rosemary Holt, Sven Boelte, Jan K. Buitelaar, Jilly Naaijen
Summary: The E/I imbalance hypothesis suggests that the imbalance between excitatory and inhibitory mechanisms underlies the behavioral characteristics of autism. This study used innovative analysis methods to investigate the relationships between genetic variance, brain structure, and autism symptomatology. The results suggest complex relationships between E/I-related genetics and autism symptom profiles as well as brain structure alterations.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Charlotte Pretzsch, Dorothea Floris, Tim V. Schaefer, Anke H. Bletsch, Caroline Gurr, Michael Lombardo, Chris Chatham, Julian Tillmann, Tony Charman, Martina Arenella, Emily Jones, Sara Ambrosino, Thomas S. Bourgeron, Guillaume Dumas, Freddy Cliquet, Claire K. Leblond, Eva Loth, Bethany F. Oakley, Jan M. Buitelaar, Simon Baron-Cohen, Christian Beckmann, Antonio M. Persico, Tobias Banaschewski, Sarah Durston, Christine Freitag, Declan G. M. Murphy, Christine Ecker
Summary: Individuals with autism spectrum disorder show significant variation in clinical outcomes, which is crucial to understand for developing precision-medicine approaches. This study found that distinct neuroanatomical and genetic profiles are associated with different adaptive behavior changes in autistic individuals, suggesting potential targets for interventions.
MOLECULAR PSYCHIATRY
(2023)
Review
Immunology
Martina Arenella, Rugile Matuleviciute, Ryad Tamouza, Marion Leboyer, Grainne Mcalonan, Janita Bralten, Declan Murphy
Summary: The article discusses the genetic factors underlying autism spectrum disorder (ASD), highlighting the role of the immune system and its genetic regulators. Through a systematic review of previous studies, the researchers identified immune genes relevant to ASD and found that these genes not only regulate immune function but also control neurodevelopment processes. The findings suggest that perturbations in immune genes may contribute to ASD by affecting typical neurodevelopment trajectories.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Siofra Heraty, Alexandra Lautarescu, David Belton, Alison Boyle, Pietro Cirrincione, Mary Doherty, Sarah Douglas, Jan Roderik Derk Plas, Katrien Van Den Bosch, Pierre Violland, Jerneja Tercon, Amber Ruigrok, Declan G. M. Murphy, Thomas Bourgeron, Christopher Chatham, Eva Loth, Bethany Oakley, Grainne M. Mcalonan, Tony Charman, Nicolaas Puts, Louise Gallagher, Emily J. H. Jones
Summary: A change in research culture is needed to improve the relationship between autistic people and the biomedical research community. Through participatory research, we can reject negative perceptions of autism and work towards a shared vision that embraces neurodiversity.
Article
Genetics & Heredity
A. M. van Eeghen, D. Stemkens, Jose Ramon Fernandez-Fructuoso, A. Maruani, K. Hadzsiev, I. D. C. van Balkom
Summary: This paper proposes consensus recommendations for the organization of care for individuals with Phelan-McDermid syndrome (PMS), emphasizing the need for expert and multidisciplinary care. The care framework is placed within the International Classification of Functioning, Disability and Health (ICF) to comprehensively assess functioning and disability. Different care roles and disciplines participating in a multidisciplinary team are described, along with recommendations for transition from pediatric to adult care. These care propositions may also be applicable to individuals with other rare genetic neurodevelopmental disorders.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Psychiatry
Qiyun Huang, Hester Velthuis, Andreia C. Pereira, Jumana Ahmad, Samuel F. Cooke, Claire L. Ellis, Francesca M. Ponteduro, Nicolaas A. J. Puts, Mihail Dimitrov, Dafnis Batalle, Nichol M. L. Wong, Lukasz Kowalewski, Glynis Ivin, Eileen Daly, Declan G. M. Murphy, Grainne M. Mcalonan
Summary: This study evaluated the role of GABA in auditory repetition suppression in individuals with autism spectrum disorder (ASD). The results showed weaker suppression of auditory responses in individuals with ASD, but this suppression could be reversed by treatment with arbaclofen, a GABA receptor agonist. These findings suggest that GABA dysfunction contributes to alterations in auditory sensory processing in ASD and targeting GABA activity may be a potential therapeutic approach.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Psychiatry
Valeria Parlatini, Joaquim Radua, Aleix Solanes Font, Rob Wichers, Stefanos Maltezos, Masafumi Sanefuji, Flavio Dell'Acqua, Marco Catani, Michel Thiebaut de Schotten, Declan Murphy
Summary: This longitudinal study found an association between pre-treatment anatomy of the fronto-striatal and fronto-parietal attentional networks and methylphenidate (MPH) treatment response in adults. Specifically, a smaller left dorsal superior longitudinal fasciculus (SLF I) was associated with a lower probability of responding to two-month MPH treatment. Only non-responders significantly differed from controls in this tract metric. Additionally, machine learning identified clinical and neuropsychological factors associated with treatment response.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Immunology
Martina Arenella, Giuseppe Fanelli, Lambertus A. Kiemeney, Grainne Mcalonan, Declan G. Murphy, Janita Bralten
Summary: Autism spectrum disorder (ASD) is a common and complex neurodevelopmental condition. The pathophysiology of ASD is poorly defined, but a strong genetic component and immune dysregulation are believed to play a role. This study found a positive correlation between ASD and allergic diseases (ALG), but negative correlations with lymphocyte count, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Additionally, specific genetic loci related to RA, C-reactive protein, and granulocytes and lymphocyte counts were found to be correlated with ASD. In the general population, increased genetic liability for SLE, RA, ALG, and lymphocyte levels was associated with autistic traits, particularly rigidity and childhood behavior.
BRAIN BEHAVIOR & IMMUNITY-HEALTH
(2023)
Article
Anatomy & Morphology
Stefano Sandrone, Marco Aiello, Carlo Cavaliere, Michel Thiebaut de Schotten, Katja Reimann, Claire Troakes, Istvan Bodi, Luis Lacerda, Serena Monti, Declan Murphy, Stefan Geyer, Marco Catani, Flavio Dell'Acqua
Summary: The histological validity of T1w/T2w myelin mapping in white matter was explored by comparing it with ex vivo postmortem histology and in vivo MRI methods (QSM and multi-echo T2 MWF mapping techniques). The results show a discrepancy between T1w/T2w myelin maps and histology, suggesting caution in using T1w/T2w as a white matter mapping method at the callosal level.
BRAIN STRUCTURE & FUNCTION
(2023)
Article
Psychiatry
Maria A. Mendez, Bethany Oakley, Roberto Canitano, Antonia San Jose-Caceres, Michela Tinelli, Martin Knapp, James Cusack, Mara Parellada, Pierre Violland, Jan R. Derk Plas, Ricardo Canal-Bedia, Alvaro Bejarano-Martin, Declan G. M. Murphy, Vinciane Quoidbach, Celso Arango
Summary: There is a lack of harmonized guidelines in Europe for early detection, diagnosis, and intervention for autism, leading to unsatisfactory experiences for autistic individuals and their caregivers. The analysis of care pathways in Italy, Spain, and the UK revealed long wait times for screening and diagnosis, limited information and support, and deficient family support throughout the journey.
EUROPEAN PSYCHIATRY
(2023)
Article
Psychiatry
Michela Tinelli, Aine Roddy, Martin Knapp, Celso Arango, Maria Andreina Mendez, James Cusack, Declan Murphy, Roberto Canitano, Bethany Oakley, Vinciane Quoidbach
Summary: This study used simulation modeling to analyze the long-term cost-effectiveness of the Preschool Autism Communication Trial (PACT). The results showed that PACT is cost-saving over time from a societal perspective, particularly after 6 years, as it reduces the costs of unpaid care provided by parents.
EUROPEAN PSYCHIATRY
(2023)