Review
Cell Biology
Claudio D'Incal, Jitse Broos, Thierry Torfs, R. Frank Kooy, Wim Vanden Berghe
Summary: FMRP plays a crucial role in neuronal development and synapse formation, with its absence affecting multiple cellular pathways, particularly neurotransmitter receptors and intracellular signaling molecules. By utilizing quantitative proteomic and phosphoproteomic studies, novel targets for treating Fragile X syndrome may be identified.
Article
Psychiatry
Sneha Shah, Joel D. Richter
Summary: Fragile X Syndrome results from the silence of the FMR1 gene, leading to loss of the FMRP protein in the brain and affecting mRNA translation. Aberrant splicing changes in Fmr1-deficient mice are related to those found in individuals with autism spectrum disorders and mouse models of intellectual disability. Splicing aberrations in these disorders may play a role in shared pathophysiological conditions and cognitive impairments.
FRONTIERS IN PSYCHIATRY
(2021)
Review
Psychology, Multidisciplinary
Anne Hoffmann
Summary: Fragile X syndrome is a common cause of inherited intellectual disability and is often associated with a high rate of autism. Language delays are observed in various areas, including overall communication, receptive and expressive language, pragmatic language, speech sounds, and literacy. Individuals diagnosed with both fragile X syndrome and autism tend to have more significant intellectual disability and language disorder. This study explores the language phenotype of fragile X syndrome and highlights the roles of cognition, autistic symptomatology, and gender. Implications for assessment and intervention approaches based on the strengths and weaknesses of the fragile X syndrome language phenotype are discussed.
FRONTIERS IN PSYCHOLOGY
(2022)
Article
Genetics & Heredity
Reymundo Lozano, Talia Thompson, Jayne Dixon-Weber, Craig A. Erickson, Elizabeth Berry-Kravis, Sara Williams, Elizabeth Smith, Jean A. Frazier, Hilary Rosselot, Cristan Farmer, David Hessl
Summary: Research indicates that individuals with fragile X syndrome commonly experience high levels of chronic anxiety, which is difficult to measure due to their inability to reliably report internal emotional or body states. Survey results from caregivers and self-advocates revealed various behavioral indicators of anxiety, such as irritability, aggression, and physical symptoms, supporting the need for an anxiety measure for FXS that minimizes problems with rater inference.
Review
Biochemistry & Molecular Biology
Sarah Larrigan, Sujay Shah, Alex Fernandes, Pierre Mattar
Summary: During brain development, the genome is repeatedly reconfigured to aid neuronal and glial differentiation, with a range of chromatin remodeling complexes facilitating the process. The non-redundancy of these complexes suggests a need for a variety of remodelers with different specificities and activities in neurodevelopment. The nucleosome remodeling and deacetylase (NuRD) complex plays a key role in the biochemistry, genetics, and functions of neural progenitors and neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Kaylynn Shuleski, Laura Zalles, Reymundo Lozano
Summary: This study explores the concerns and challenges caregivers of individuals affected by Fragile X Syndrome (FXS) encounter when considering long-term support plans. Most FXS individuals currently live with family due to various reasons, such as parental desire and inability to live independently. Caregivers are concerned about multiple aspects of the individuals' future, with higher levels of concern for younger individuals.
Article
Psychiatry
David C. Stoppel, Patrick K. McCamphill, Rebecca K. Senter, Arnold J. Heynen, Mark F. Bear
Summary: Fragile X syndrome is caused by silencing of the human FMR1 gene and is the leading monogenic cause of intellectual disability and autism. Studies indicate that long-term use of mGluR5 NAMs may lead to the development of treatment resistance, likely occurring at signaling nodes downstream.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
David E. Godler, Yoshimi Inaba, Minh Q. Bui, David Francis, Cindy Skinner, Charles E. Schwartz, David J. Amor
Summary: This study characterizes the specific DNA methylation patterns of fragile X syndrome in blood and brain tissues, providing a novel avenue for the detection of the syndrome through DNA methylation analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Camille Champigny, Florence Morin-Parent, Laurence Bellehumeur-Lefebvre, Artuela Caku, Jean-Francois Lepage, Francois Corbin
Summary: This study evaluated the safety and efficacy of combined treatment with lovastatin and minocycline for patients with FXS. The results showed that the combination therapy was safe and improved several aspects of behavior. These findings lay the groundwork for further placebo-controlled double-blind clinical trials to confirm the benefits of the combined therapy.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Psychiatry
Truong An Bui, Julie Shatto, Tania Cuppens, Arnaud Droit, Francois V. Bolduc
Summary: The article discusses the wide range of phenotypes associated with Fragile X syndrome and calls for consideration of interactions between different phenotypes in clinical research. A new approach is proposed to better understand the effects of treatments on different individuals in clinical trials and to take individual genetic differences into account in the design.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Cell & Tissue Engineering
Ai Zhang, Irina Sokolova, Alain Domissy, Joshua Davis, Lee Rao, Kagistia Hana Utami, Yanling Wang, Randi J. Hagerman, Mahmoud A. Pouladi, Pietro Sanna, Michael J. Boland, Jeanne F. Loring
Summary: This study investigates the effects of Fragile X Syndrome (FXS) on GABAergic neurogenesis and suggests that loss of FMRP prolongs the proliferative stage of progenitors, leading to immature neurons in later stages of neurogenesis. This finding has implications for understanding the development of excitatory-inhibitory circuits in FXS and may guide therapeutic interventions.
STEM CELLS TRANSLATIONAL MEDICINE
(2022)
Article
Clinical Neurology
Kelsie A. Boulton, Adam J. Guastella, Marie-Antoinette Hodge, Eleni A. Demetriou, Natalie Ong, Natalie Silove
Summary: Children with neurodevelopmental conditions attending developmental assessment services have high rates of mental health concerns, with approximately 48% of preschool and 61% of school-age children having subclinical or clinically elevated scores. These rates remain high even after excluding items specifically related to neurodevelopmental concerns. School-aged females are more likely to have elevated internalizing problems compared to males (67% vs 48%). Children with multiple DSM-5 diagnoses also show a greater rate of subclinical or clinically elevated scores. These findings highlight the importance of identifying and addressing mental health concerns in children attending developmental assessment services.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Lucia Pia Bruno, Gabriella Doddato, Floriana Valentino, Margherita Baldassarri, Rossella Tita, Chiara Fallerini, Mirella Bruttini, Caterina Lo Rizzo, Maria Antonietta Mencarelli, Francesca Mari, Anna Maria Pinto, Francesca Fava, Alessandra Fabbiani, Vittoria Lamacchia, Anna Carrer, Valentina Caputo, Stefania Granata, Elisa Benetti, Kristina Zguro, Simone Furini, Alessandra Renieri, Francesca Ariani
Summary: Intelectual disability (ID) and autism spectrum disorder (ASD) are often associated and characterized by impairments in cognitive processes and daily life tasks. Molecular diagnosis is crucial for improving prognosis and initiating treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Sahar Javadi, Yue Li, Jie Sheng, Lucy Zhao, Yao Fu, Daifeng Wang, Xinyu Zhao
Summary: Transient Nutlin-3 treatment can prevent neurogenesis and cognitive deficits in mature adult FXS mice, potentially through modulating the adult neurogenic niche.
Article
Psychology, Developmental
Walter E. Kaufmann, Melissa Raspa, Carla M. Bann, Julia M. Gable, Holly K. Harris, Dejan B. Budimirovic, Reymundo Lozano
Summary: This study investigates behavioral subtypes of Fragile X syndrome using a pediatric cross-sectional sample. Through latent class analysis, five distinct subtypes were identified, each with unique behavioral profiles. These findings are crucial for improving clinical management and therapeutic development.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2022)
Article
Clinical Neurology
Olfa Khalfallah, Susana Barbosa, Emanuela Martinuzzi, Laetitia Davidovic, Robert Yolken, Nicolas Glaichenhaus
Summary: Most researchers in immunopsychiatry agree that severe psychiatric disorders are linked to inflammation and changes in immune variables. However, the field is facing a replication crisis due to lack of reproducibility. Current studies focus on immune variables in blood and discuss analytical methods and overlooked methodological issues.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Clinical Neurology
Andreas Brunklaus, Tobias Bruenger, Tony Feng, Carmen Fons, Anni Lehikoinen, Eleni Panagiotakaki, Mihaela-Adela Vintan, Joseph Symonds, James Andrew, Alexis Arzimanoglou, Sarah Delima, Julie Gallois, Donncha Hanrahan, Gaetan Lesca, Stewart MacLeod, Dragan Marjanovic, Amy McTague, Noemi Nunez-Enamorado, Eduardo Perez-Palma, M. Scott Perry, Karen Pysden, Sophie J. Russ-Hall, Ingrid E. Scheffer, Krystal Sully, Steffen Syrbe, Ulvi Vaher, Murugan Velayutham, Julie Vogt, Shelly Weiss, Elaine Wirrell, Sameer M. Zuberi, Dennis Lal, Rikke S. Moller, Massimo Mantegazza, Sandrine Cestele
Summary: This study describes different phenotypes of SCN1A-related epilepsy, some of which are associated with febrile seizures and familial hemiplegic migraine. The research found that these phenotypes are caused by SCN1A variants, and by conducting clinical, genetic, and functional evaluations of the affected individuals, it reveals the potential efficacy of sodium channel blockers in treating this disease.
Review
Physiology
Renzo Guerrini, Valerio Conti, Massimo Mantegazza, Simona Balestrini, Aristea S. Galanopoulou, Fabio Benfenati
Summary: Developmental and epileptic encephalopathies (DEEs) are a group of disorders characterized by early-onset severe epileptic seizures, EEG abnormalities, and developmental impairment. DEEs can be caused by genetic and nongenetic factors, with mutations in various genes playing a role. Research in animal models and clinical trials have helped uncover the pathophysiological mechanisms underlying DEEs and explore different treatment options.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Pediatrics
Aminata H. Cisse, Marion Taine, Muriel Tafflet, Blandine De Lauzon-Guillain, Karine Clement, Olfa Khalfallah, Laetitia Davidovic, Sandrine Lioret, Marie A. Charles, Barbara Heude
Summary: This study investigated the association of cord blood leptin level and the LEPR rs9436303 polymorphism with childhood adiposity. The results showed that increased leptin level was associated with lower BMI and earlier age at adiposity rebound, while rs9436303 polymorphism carriage was associated with higher BMI and later age at adiposity rebound.
Editorial Material
Clinical Neurology
Massimo Mantegazza, Sandrine Cestele
Article
Clinical Neurology
Sara Matricardi, Sandrine Cestele, Marina Trivisano, Benedetta Kassabian, Nathalie Leroudier, Roberta Vittorini, Margherita Nosadini, Elisabetta Cesaroni, Sabrina Siliquini, Cristina Marinaccio, Francesca Longaretti, Barbara Podesta, Francesca Felicia Operto, Concetta Luisi, Stefano Sartori, Clementina Boniver, Nicola Specchio, Federico Vigevano, Carla Marini, Massimo Mantegazza
Summary: This study aimed to refine the spectrum of SCN1A epileptic disorders beyond DS and GEFS+ and optimize antiseizure management. Nine of the 16 probands had de novo pathogenic variants causing DEE, while seven probands manifested focal epilepsies with mild or no intellectual disability. Sodium channel blockers never worsened seizures, and functional analysis showed a gain of channel function for three representative variants. The study highlights the wide range of SCN1A disorders and the importance of SCN1A testing in pediatric, familial and nonfamilial, focal epilepsies.
Article
Clinical Neurology
Wolfgang Strube, Aslihan Aksar, Ingrid Bauer, Susana Barbosa, Michael Benros, Christiane Blankenstein, Mattia Campana, Laetitia Davidovic, Nicolas Glaichenhaus, Peter Falkai, Thomas Gorlitz, Maximilian Hansbauer, Daniel Heilig, Olfa Khalfallah, Marion Leboyer, Emanuela Martinuzzi, Susanne Mayer, Joanna Moussiopoulou, Irina Papazova, Natasa Peric, Elias Wagner, Thomas Schneider-Axmann, Judit Simon, Alkomiet Hasan
Summary: This study aims to evaluate the efficacy, safety, and cost-effectiveness of adding 400 mg Celecoxib to the ongoing antipsychotic treatment of patients with schizophrenia spectrum disorders exhibiting an inflammatory profile. The trial will assess 199 patients for eligibility and randomize 109 patients with an inflammatory profile to receive either Celecoxib or placebo for 8 weeks. The primary endpoint is changes in symptom severity, and secondary endpoints include other measures of psychopathology and safety.
JOURNAL OF NEURAL TRANSMISSION
(2023)
Article
Biology
Louisiane Lemaire, Mathieu Desroches, Martin Krupa, Massimo Mantegazza
Summary: Na(V)1.1 is a voltage-gated sodium channel mainly expressed in GABAergic neurons. Loss of function mutations cause epileptic disorders, while gain of function mutations cause migraine with cortical spreading depolarizations (CSDs). The mechanisms behind these opposite effects are still debated.
JOURNAL OF MATHEMATICAL BIOLOGY
(2023)
Article
Neurosciences
Paolo Scalmani, Rosina Paterra, Massimo Mantegazza, Massimo Avoli, Marco de Curtis
Summary: Single-unit recordings in temporal lobe epilepsy patients and models of temporal lobe seizures showed that interneurons are active during focal seizure onset. This study performed simultaneous patch-clamp and field potential recordings in entorhinal cortex slices of mice to analyze the activity of specific interneuron (IN) subpopulations during acute seizure-like events (SLEs) induced by 4-aminopyridine (4-AP). The results revealed that entorhinal cortex INs are highly active at the onset and during the progression of 4-AP-induced SLEs.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Environmental Sciences
Olfa Khalfallah, Susana Barbosa, Claire Phillippat, Remy Slama, Cedric Galera, Barbara Heude, Nicolas Glaichenhaus, Laetitia Davidovic
Summary: Childhood internalizing disorders are negatively focused behaviors such as anxiety, depression, and somatic complaints. A mixture of endocrine disruptors (EDs) during prenatal exposure has limited effects on internalizing behaviors in boys at age 3, and pro-inflammatory cytokines IL-beta, IL-6, and TNF-alpha are unlikely mediators of this effect. Further studies are needed to understand the deleterious effects of ED mixtures on internalizing behaviors and identify possible mediating pathways.
ENVIRONMENTAL RESEARCH
(2023)
Review
Clinical Neurology
Jonathon Smith, George Richerson, Hayet Kouchi, Fabrice Duprat, Massimo Mantegazza, Laurent Bezin, Sylvain Rheims
Summary: Although animal models have contributed to our understanding of the pathophysiology of SUDEP, specific prevention strategies are still lacking. It is important to consider the advantages and limitations of different models and their relevance to the human situation when interpreting preclinical data.
Article
Clinical Neurology
Anna-Maria Katsarou, Hana Kubova, Stephane Auvin, Massimo Mantegazza, Melissa Barker-Haliski, Aristea S. Galanopoulou, Christopher A. Reid, Bridgette D. Semple
Summary: This article describes a study on pediatric acquired epilepsy models. The authors have developed a series of case report forms to improve standardization and transparency across laboratories, and to support the goal of improving pediatric patient outcomes and minimizing the burden of epilepsy.
Article
Clinical Neurology
Massimo Mantegazza, Stephane Auvin, Melissa Barker-Haliski, Anna-Maria Katsarou, Hana Kubova, Aristea S. Galanopoulou, Bridgette Semple, Christopher A. Reid
Summary: Rodent models are essential for studying genetic epilepsy, but the reproducibility of experiments using these models is still an issue. This study introduces two case report forms for documenting data elements in genetic rodent models. These forms help researchers consistently describe experimental data and improve the reproducibility and translational impact of studies.