Review
Immunology
Bruno Bonnechere, Najaf Amin, Cornelia van Duijn
Summary: The study reviewed different microbiota involved in neuropsychiatric diseases and assessed the overlap between different pathologies. The findings provide new insights into the complex relationship between the brain and the gut and the implications in neuropsychiatric pathologies. The identification of unique signatures in neuropsychiatric diseases suggests new possibilities in targeted anti or probiotic treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Psychology, Developmental
Melissa H. H. Black, Dana L. L. Greenwood, Jerome Choo Chen Hwa, Jacqueline Pivac, Jessica Tang, Patrick J. F. Clarke
Summary: Autistic adults commonly experience higher levels of worry than non-autistic adults, impacting their daily life activities, sleep, and mental health. The content and extent of worry in autistic adults were found to be clinically significant, with negative thoughts forming a cycle of worry for them. This study highlights the importance of understanding and addressing anxiety in autistic adults.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2023)
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)
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)
Article
Psychiatry
Eberhard David, Billstedt Eva, Gillberg Christopher
Summary: Missed cases of neurodevelopmental disorders (NDDs) within adult psychiatry services have attracted increasing attention. This study found that almost two thirds of first-time attenders at an adult psychiatry clinic met criteria for ADHD or ASD. Most of the patients with NDD had not been diagnosed in childhood. The results underscore the importance of screening for NDD in adult psychiatric services.
PSYCHIATRY RESEARCH
(2022)
Article
Cell Biology
Ilaria Parenti, Elsa Leitao, Alma Kuechler, Laurent Villard, Cyril Goizet, Cecile Courdier, Allan Bayat, Alessandra Rossi, Sophie Julia, Ange-Line Bruel, Frederic Tran Mau-Them, Sophie Nambot, Daphne Lehalle, Marjolaine Willems, James Lespinasse, Jamal Ghoumid, Roseline Caumes, Thomas Smol, Salima El Chehadeh, Elise Schaefer, Marie-Therese Abi-Warde, Boris Keren, Alexandra Afenjar, Anne-Claude Tabet, Jonathan Levy, Anna Maruani, Angel Aledo-Serrano, Waltraud Garming, Clara Milleret-Pignot, Anna Chassevent, Marije Koopmans, Nienke E. Verbeek, Richard Person, Rebecca Belles, Gary Bellus, Bonnie A. Salbert, Frank J. Kaiser, Laure Mazzola, Philippe Convers, Laurine Perrin, Amelie Piton, Gert Wiegand, Andrea Accogli, Francesco Brancati, Fabio Benfenati, Nicolas Chatron, David Lewis-Smith, Rhys H. Thomas, Federico Zara, Pasquale Striano, Gaetan Lesca, Christel Depienne
Summary: This study expands on the clinical and molecular spectrum of SYN1-related neurodevelopmental disorders and provides analysis on the association between these disorders and features such as epilepsy and intellectual disability. Additionally, the study reveals an association between early seizure onset and more severe impairment of cognitive functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Psychology, Developmental
Courtney J. Bernardin, Timothy Lewis, Debora Bell, Stephen Kanne
Summary: Autistic individuals experience higher rates of psychiatric comorbidities, with camouflaging potentially being detrimental to mental health, especially for females. The level of camouflaging predicts depression, anxiety, and stress in both autistic and non-autistic adolescents, suggesting interventions focusing on social skills, self-acceptance, and self-esteem may help reduce negative effects of camouflaging.
Article
Psychology, Clinical
Shrujna Patel, Matthew N. Cooper, Hannah Jones, Andrew J. O. Whitehouse, Russell C. Dale, Adam J. Guastella
Summary: Research suggests that maternal immune activation (MIA) may be associated with increased behavioral and emotional problems in offspring, particularly related to conditions like asthma and allergies. Gender differences were observed in the psychological effects of MIA on males and females.
PSYCHOLOGICAL MEDICINE
(2021)
Article
Public, Environmental & Occupational Health
Ali J. Alsaad, Mujtaba M. Al Khamees, Abdulelah N. Alkadi, Majd A. Alsaleh, Aeshah S. Alshairdah, Zahra'a A. Alessa
Summary: This study aimed to measure the prevalence rates of depression and anxiety among parents of children with different NDDs, compare the rates between mothers and fathers, and measure the relevant associated factors. The study found that 85.1% of parents of children with NDDs had depression, and 85.8% had anxiety.
Review
Biology
Miriam D. Lense, Eniko Ladanyi, Tal-Chen Rabinowitch, Laurel Trainor, Reyna Gordon
Summary: This article discusses the impact of neurodevelopmental disorders on children, pointing out that these disorders may involve different impairments in social, cognitive, and motor functioning, as well as comorbidities between different disorders. The article also explores difficulties related to rhythm, timing, and synchrony skills, and how these impairments may affect various NDDs.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Review
Genetics & Heredity
Liliana Rojas-Charry, Leonardo Nardi, Axel Methner, Michael J. Schmeisser
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impairments in social interaction and repetitive behaviors, with mitochondrial dysfunction considered as an important underlying pathogenic factor. However, the pathophysiology of ASD is still not fully understood, with mutations in synaptic genes also playing a role in the disorder. Mitochondria play diverse functions at the synapse, beyond their classical role as energy providers.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Review
Psychology, Developmental
Ellen Kelson, Diana Dorstyn
Summary: This review quantitatively evaluated telehealth trials aimed at promoting caregivers' mental health. The findings suggest that psychological interventions delivered by telephone and/or the internet can effectively manage caregivers' mental health symptoms, although the longevity of these effects remains uncertain.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2023)
Article
Psychiatry
Sabrina Doering, Paul Lichtenstein, Christopher Gillberg, Ralf Kuja-Halkola, Sebastian Lundstrom
Summary: Adolescent internalizing problems like anxiety and depression are negatively associated with educational outcomes in later adolescence, with genetic factors accounting for a large proportion of this correlation. Internalizing problems are an important risk factor for subsequent educational underachievement, surpassing the risk conferred by childhood genetic factors.
PSYCHIATRY RESEARCH
(2021)
Review
Psychiatry
Wenting Zhuang, Tong Ye, Wei Wang, Weihong Song, Tao Tan
Summary: CTNNB1 is a gene that encodes b-catenin and plays a crucial role in the Wnt signaling pathway, regulating cellular homeostasis. While most studies on CTNNB1 have focused on its role in cancer, it has recently been found to be involved in neurodevelopmental disorders (NDDs) such as intellectual disability, autism, and schizophrenia. Mutations in CTNNB1 disrupt the Wnt signaling pathway, leading to abnormalities in gene transcription, synaptic plasticity, neuronal apoptosis, and neurogenesis. This review explores various aspects of CTNNB1 and its physiological and pathological functions in the brain, as well as recent research on its expression and function in NDDs. The findings suggest that CTNNB1 might be one of the top high-risk genes for NDDs and a potential therapeutic target for their treatment.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Multidisciplinary Sciences
Yujie Liang, Hong Yu, Xiaoyin Ke, Darryl Eyles, Ruoyu Sun, Zichen Wang, Saijun Huang, Ling Lin, John J. McGrath, Jianping Lu, Xiaoling Guo, Paul Yao
Summary: This study suggests that vitamin D deficiency may exacerbate autism-related phenotypes induced by maternal diabetes, primarily through epigenetic mechanisms.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Review
Neurosciences
Konstanze Simbriger, Ines S. Amorim, Gilliard Lach, Kleanthi Chalkiadaki, Stella Kouloulia, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: Contextual fear conditioning is a common behavioral paradigm used in neuroscience research to study the mechanisms of learning and memory. Using ribosome profiling, a study demonstrated that an immediate shock in male mice leads to translational and transcriptional changes in Immediate Early Genes in the dorsal hippocampus, an effect often overlooked in research.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Cell Biology
Mehdi Hooshmandi, Vinh Tai Truong, Eviatar Fields, Riya Elizabeth Thomas, Calvin Wong, Vijendra Sharma, Ilse Gantois, Patricia Soriano Roque, Kleanthi Chalkiadaki, Neil Wu, Anindyo Chakraborty, Soroush Tahmasebi, Masha Prager-Khoutorsky, Nahum Sonenberg, Aparna Suvrathan, Alanna J. Watt, Christos G. Gkogkas, Arkady Khoutorsky
Summary: Recent studies have shown that overactivated mTORC1 in the cerebellum can lead to autism-like features and cognitive deficits, whereas ablation of 4E-BP2 in Purkinje cells causes reduced cell numbers, increased regularity of action potential firing, and deficits in motor learning. Surprisingly, mice with selective ablation of 4E-BP2 exhibit impaired spatial memory but normal social interaction and no deficits in repetitive behavior, suggesting independent cerebellar mechanisms controlling social behavior and memory formation downstream of mTORC1/4E-BP2.
Article
Multidisciplinary Sciences
Patricia Soriano Roque, Mehdi Hooshmandi, Laura Neagu-Lund, Shelly Yin, Noosha Yousefpour, Hiroaki Sato, Tamaki Sato, Yosuke Nakadate, Akiko Kawakami, Soroush Tahmasebi, Alfredo Ribeiro-da-Silva, Christos G. Gkogkas, Masha Prager-Khoutorsky, Thomas Schricker, Linda Wykes, Arkady Khoutorsky
Summary: The study showed that intranasal insulin administration to juvenile mice can prevent cognitive impairments caused by general anesthesia, including hippocampal cell apoptosis, synaptic plasticity deficits, and memory impairment. The rescue effect is likely mediated through the mTORC1/4E-BP2 signaling pathway.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Elpida Statoulla, Kleanthi Chalkiadaki, Dimitris Karozis, Christos G. Gkogkas
Summary: Translational control of gene expression plays a crucial role in maintaining stem cell pluripotency, differentiation, and the generation of various neuronal subtypes, while also being linked to numerous brain disorders.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Dong Liu, Carmen Nanclares, Konstanze Simbriger, Kun Fang, Ethan Lorsung, Nam Le, Ines Silva Amorim, Kleanthi Chalkiadaki, Salil Saurav Pathak, Jin Li, Jonathan C. Gewirtz, Victor X. Jin, Paulo Kofuji, Alfonso Araque, Harry T. Orr, Christos G. Gkogkas, Ruifeng Cao
Summary: Research shows that disruption of the Bmal1 gene leads to social impairments, repetitive behaviors, and motor learning disabilities in mice, similar to core behavioral deficits in ASD. Abnormal cell density and morphology were found in the cerebellar Purkinje cells of Bmal1 knockout mice. Electrophysiological recordings revealed enhanced synaptic transmission and reduced firing rates in these cells. Differential expression of genes associated with ASD and ataxia and dysregulated pathways were identified in the cerebellum of Bmal1 knockout mice. The antidiabetic drug metformin was able to reverse the hyperactivation of mTORC1 and alleviate behavioral and cellular deficits in Bmal1 knockout mice. Conditional deletion of Bmal1 in cerebellar Purkinje cells alone was sufficient to replicate autistic-like behaviors and cellular changes. These findings suggest a previously unknown role for Bmal1 disruption in cerebellar dysfunction and autistic-like behaviors, providing experimental evidence for the involvement of circadian clock gene dysregulation in the pathogenesis of ASD.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Shannon Tansley, Ning Gu, Alba Urena Guzman, Weihua Cai, Calvin Wong, Kevin C. Lister, Einer Munoz-Pino, Noosha Yousefpour, R. Brian Roome, Jordyn Heal, Neil Wu, Annie Castonguay, Graham Lean, Elizabeth M. Muir, Artur Kania, Masha Prager-Khoutorsky, Ji Zhang, Christos G. Gkogkas, James W. Fawcett, Luda Diatchenko, Alfredo Ribeiro-da-Silva, Yves De Koninck, Jeffrey S. Mogil, Arkady Khoutorsky
Summary: After peripheral nerve injury, microglia degrade extracellular matrix structures (PNNs) in the spinal cord dorsal horn, enhancing the output of spinal nociceptive circuits and causing pain hypersensitivity.
Article
Clinical Neurology
Kleanthi Chalkiadaki, Mehdi Hooshmandi, Gilliard Lach, Elpida Statoulla, Konstanze Simbriger, Ines S. Amorim, Stella Kouloulia, Maria Zafeiri, Panagiotis Pothos, Eric Bonneil, Ilse Gantois, Jelena Popic, Sung-Hoon Kim, Calvin Wong, Ruifeng Cao, Noboru H. Komiyama, Yaser Atlasi, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: MAPK interacting protein kinases 1 and 2 (Mnk1/2) regulate various functions by phosphorylating their substrate eIF4E on Ser209. Deletion of Mnk1/2 impairs synaptic plasticity and memory in mice, but ablation of phospho-eIF4E (Ser209) has no effect on these processes, indicating that Mnk1/2 have additional downstream effectors in the brain. Synaptic Ras GTPase activating protein 1 (Syngap1), encoded by an autism gene, is identified as a downstream target of Mnk1. Knockdown of Syngap1 reverses memory deficits in Mnk double knockout mice and pharmacological inhibition of Mnks rescues autism-related phenotypes in Syngap1(+/-) mice.
Article
Neurosciences
Mina N. Anadolu, Jingyu Sun, Senthilkumar Kailasam, Kleanthi Chalkiadaki, Konstanze Krimbacher, Jewel T. -Y. Li, Teodora Markova, Seyed M. Jafarnejad, Francois Lefebvre, Joaquin Ortega, Christos G. Gkogkas, Wayne S. Sossin
Summary: The granule fraction contains proteins implicated in stalled polysome function, and the ribosomes in this fraction are mainly stalled in the hybrid state. Ribosome profiling reveals longer footprints on mRNAs associated with FMRPs and an increase in ribosome occupancy on mRNAs encoding RNA binding proteins. The data supports a model in which specific sequences in mRNAs stall ribosomes during translation elongation in neurons.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Ines S. Amorim, Sylvie Challal, Laetitia Cistarelli, Thierry Dorval, Laurene Abjean, Manuelle Touzard, Nicolas Arbez, Arnaud Francois, Fany Panayi, Ross Jeggo, Erika Cecon, Atsuro Oishi, Julie Dam, Ralf Jockers, Patricia Machado
Summary: This article describes a method for establishing a neuronal model of Tau protein accumulation, which can be used for drug discovery and therapeutic research.
Article
Cell Biology
Kleanthi Chalkiadaki, Elpida Statoulla, Maria Zafeiri, Nabila Haji, Jean-Claude Lacaille, Craig M. Powell, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: Inhibition of Nlgn1 expression in TSC mouse models can rescue cognitive and social behavior deficits without affecting mTORC1 hyperactivation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Sudarshan Patil, Kleanthi Chalkiadaki, Tadiwos F. Mergiya, Konstanze Krimbacher, Ines S. Amorim, Shreeram Akerkar, Christos G. Gkogkas, Clive R. Bramham
Summary: The phosphorylation of eIF4E plays a critical role in the translational control of long-term synaptic plasticity and the selective translation of the Wnt signaling pathway. Phospho-ablated Eif4e(S209A) Knockin mice exhibit impaired maintenance of dentate gyrus LTP, while the basal perforant path-evoked transmission and LTP induction are unaffected. These findings suggest that activity-induced eIF4E phosphorylation is essential for LTP maintenance and the regulation of the mRNA cap-binding complex.
Article
Medicine, Research & Experimental
Patricia Soriano Roque, Carolina Thorn Perez, Mehdi Hooshmandi, Calvin Wong, Mohammad Javad Eslamizade, Shilan Heshmati, Nicole Brown, Vijendra Sharma, Kevin C. Lister, Vanessa Magalie Goyon, Laura Neagu-Lund, Cathy Shen, Nicolas Daccache, Hiroaki Sato, Tamaki Sato, Jeffrey S. Mogil, Karim Nader, Christos G. Gkogkas, Mihaela D. Iordanova, Masha Prager-Khoutorsky, Heidi M. McBride, Jean-Claude Lacaille, Linda Wykes, Thomas Schricker, Arkady Khoutorsky
Summary: Repeated or prolonged general anesthesia during the early postnatal period leads to long-lasting impairments in memory formation by causing selective apoptosis and loss of parvalbumin-positive inhibitory interneurons in the hippocampus of mice. This loss disrupts the regulation of neuronal circuits and memory consolidation. Preventing the loss of parvalbumin neurons rescues anesthesia-induced deficits in pyramidal cell inhibition and long-term memory, while partial depletion of these neurons in neonates is sufficient to impair long-term memory.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
