Article
Biochemistry & Molecular Biology
Krzysztof Maria Wilczynski, Aleksandra Augusciak-Duma, Aleksandra Stasik, Lena Cichon, Alicja Kawalec, Malgorzata Janas-Kozik
Summary: Autism spectrum disorder is a complex neurodevelopmental disorder that affects social interactions, communication, and behavior. This study found that the balance between the expression levels of the CD38 gene and the oxytocinase gene plays a key role in the risk and clinical presentation of ASD.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Review
Neurosciences
Haruhiro Higashida, Kazumi Furuhara, Olga Lopatina, Maria Gerasimenko, Osamu Hori, Tsuyoshi Hattori, Yasuhiko Hayashi, Stanislav M. Cherepanov, Anna A. Shabalova, Alla B. Salmina, Kana Minami, Teruko Yuhi, Chiharu Tsuji, PinYue Fu, Zhongyu Liu, Shuxin Luo, Anpei Zhang, Shigeru Yokoyama, Satoshi Shuto, Mizuki Watanabe, Koichi Fujiwara, Sei-ichi Munesue, Ai Harashima, Yasuhiko Yamamoto
Summary: Understanding the neurocircuitry and synaptic sites of action of oxytocin (OT) in the brain is vital to comprehend its role in social memory and behavior. Additionally, investigating the transport of OT to the brain from the peripheral circulation is equally important. Studies suggest that CD38, CD157, and receptor for advanced glycation end-products (RAGE) regulate OT concentrations in the brain and blood. RAGE facilitates the uptake of OT from mother's milk and recruits circulating OT into the brain. It is also found that administration of nicotinamide riboside increases brain OT levels. This research provides insights into the involvement of RAGE in OT regulation and other possible routes of OT recruitment to the brain.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Sarah Morson, Yifei Yang, David J. Price, Thomas Pratt
Summary: The 16p11.2 CNV affects the gene dosage of 29 protein coding genes, potentially contributing to ASD symptoms, with genes such as KIF22 and ALDOA being significantly expressed in neural progenitors.
Review
Biochemistry & Molecular Biology
Anastasia S. Tsingotjidou
Summary: Oxytocin is a hormone secreted from specific neuroendocrine neurons in the hypothalamus, primarily involved in uterine contraction and breastfeeding. Additionally, it has been found to prevent degenerative disorders. This review summarizes previous studies, presents the results of oxytocin intervention and treatment, and proposes a possible connection between oxytocin's well-known functions and other diverse actions.
Article
Neurosciences
Krzysztof M. Wilczynski, Aleksandra Stasik, Lena Cichon, Aleksandra Augusciak-Duma, Malgorzata Janas-Kozik
Summary: Autism spectrum disorders (ASD) are a heterogeneous group of disorders that affect every population. Its pathogenesis involves the interaction of genetic and environmental factors. Social communication deficits are the main symptom of ASD, which lead to difficulties in everyday functioning.
Article
Neurosciences
Tobias Grossmann, Adrienne Wood
Summary: This study found that genetic variability in the oxytocin system is associated with individual differences in expressing positive affect in human infants. The CD38 gene variation was linked to higher rates of positive affective displays among 7-month-old infants. Additionally, infants with increased levels of positive affect showed enhanced brain responses when observing others smile.
SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
(2023)
Article
Psychology, Biological
Carles Tapias-Espinosa, Toni Canete, Daniel Sampedro-Viana, Tomasz Brudek, Anna Kaihoj, Ignasi Oliveras, Adolf Tobena, Susana Aznar, Alberto Fernandez-Teruel
Summary: The study examined the effects of peripheral oxytocin administration on PPI in inbred and outbred rats, showing that oxytocin increased PPI in outbred rats and attenuated PPI deficits in inbred rats. The differential effects were associated with basal differences in oxytocin-mediated mechanisms in the mPFC, demonstrating potential antipsychotic-like effects of oxytocin.
PHYSIOLOGY & BEHAVIOR
(2021)
Article
Clinical Neurology
Hidenori Yamasue, Masaki Kojima, Hitoshi Kuwabara, Miho Kuroda, Kaori Matsumoto, Chieko Kanai, Naoko Inada, Keiho Owada, Keiko Ochi, Nobutaka Ono, Seico Benner, Tomoyasu Wakuda, Yosuke Kameno, Jun Inoue, Taeko Harada, Kenji Tsuchiya, Kazuo Umemura, Aya Yamauchi, Nanayo Ogawa, Itaru Kushima, Norio Ozaki, Satoshi Suyama, Takuya Saito, Yukari Uemura, Junko Hamada, Yukiko Kano, Nami Honda, Saya Kikuchi, Moe Seto, Hiroaki Tomita, Noriko Miyoshi, Megumi Matsumoto, Yuko Kawaguchi, Koji Kanai, Manabu Ikeda, Itta Nakamura, Shuichi Isomura, Yoji Hirano, Toshiaki Onitsuka, Hirotaka Kosaka, Takashi Okada
Summary: Intranasal oxytocin has the potential to be a novel therapy for autism spectrum disorder, but the efficacy of repeated administrations is inconsistent. This study tested the effect of TTA-121, a new formulation of intranasal oxytocin with improved bioavailability, on the core symptoms of autism spectrum disorder and determined the dose-response relationship. The findings showed that TTA-121 at a dose of 6 U per day significantly improved the reciprocity score, indicating potential benefits for individuals with autism spectrum disorder.
Article
Pharmacology & Pharmacy
S. Alhazmi, B. Aljahdli, R. Farsi, M. Alharbi, K. Algothmi, N. Alburae, M. Ganash, S. Azhari, F. Basingab, A. Almuhammadi, A. Alqosaibi, H. Alkhatabi, A. Elaimi, M. Jan, H. Aldhalaan, R. Alyoubi, A. Alrafiah, A. Alrofaidi
Summary: This study investigated the use of DNA methylation and copy number variation (CNV) in the diagnosis of Autism Spectrum Disorder (ASD). The results identified CNVs in chromosome 14 that may be a potential target for ASD diagnosis, and showed an increase in methylation levels in these CNV regions. Further research is needed to determine the affected biological pathways.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2022)
Article
Genetics & Heredity
Tapasya Pal, Kathryn J. Laloli, Cushla A. Moscrip, Pawel K. Olszewski, Anica Klockars
Summary: A core yet understudied symptom of autism is aberrant eating behavior. Utilizing a model of autism, researchers examined the intake of "bland" chow in autistic rats and found that they ate less than healthy controls. They also found dysregulation in hunger processing and abnormal activation of central sites controlling appetite in the autistic rats. These findings suggest that hunger processing is dysregulated in autism and may contribute to aberrant eating behavior.
Article
Biochemistry & Molecular Biology
Magdalena Meyer, Benjamin Jurek, Mercedes Alfonso-Prieto, Rui Ribeiro, Vladimir M. Milenkovic, Julia Winter, Petra Hoffmann, Christian H. Wetzel, Alejandro Giorgetti, Paolo Carloni, Inga D. Neumann
Summary: This study reveals the cellular mechanism linking the oxytocin receptor gene mutation (OXTR rs4686302 SNP) with genetic dysregulations associated with autism spectrum disorder (ASD). The mutation leads to increased OXTR protein stability, changes in Ca2+ dynamics, and reduced activation of the MAPK pathway. Whole-genome and RNA sequencing analysis showed numerous differentially regulated genes in the mutant cells, including 429 genes associated with ASD. Computational modeling suggested that the OXTR mutation affects downstream events by altering receptor activation and signaling, consistent with the in vitro results.
MOLECULAR PSYCHIATRY
(2022)
Review
Biochemical Research Methods
Ryley Dorney, Bijay P. Dhungel, John E. J. Rasko, Lionel Hebbard, Ulf Schmitz
Summary: This review highlights the importance of gene fusions in cancer, including chromosomal rearrangement-independent fusion transcripts and complex fusion structures. It proposes a classification system for gene and transcript fusions and discusses the use of long-read sequencing and bioinformatic tools to detect and characterize fusions.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Psychiatry
Sergey Tereshchenko, Edward Kasparov, Svetlana Zobova, Marina Smolnikova, Lidia Evert, Nadezhda Semenova, Olga Zaitseva, Margarita Shubina, Nina Gorbacheva, Ludmila Lapteva
Summary: This study investigated the association between polymorphisms of CD38 and OXTR genes and SDQ scales in urban Siberian adolescents, finding no significant correlation between genotypes and SDQ results. However, high activity in the OT pathway may lead to negative consequences, such as emotional instability in older adolescent boys. Further replication studies with larger samples and greater statistical power are recommended to explore small effects, especially in different age and sex subgroups of adolescents.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Neurosciences
Li-Ping Shen, Wei Li, Ling-Zhu Pei, Jun Yin, Shu-Tao Xie, Hong-Zhao Li, Chao Yan, Jian-Jun Wang, Qipeng Zhang, Xiao-Yang Zhang, Jing-Ning Zhu
Summary: The study found that oxytocin receptors are present in the cerebellar lobule Crus I of individuals with autism spectrum disorders. However, activation of these receptors did not affect normal functioning and did not improve abnormal behaviors in an autism mouse model. Therefore, the researchers concluded that oxytocin signaling in this area may not be involved in the pathophysiology of autism.
Article
Biochemistry & Molecular Biology
Milos Kostic, Joseph J. Raymond, Christophe A. C. Freyre, Beata Henry, Tayfun Tumkaya, Jivan Khlghatyan, Jill Dvornik, Jingyao Li, Jack S. Hsiao, Seon Hye Cheon, Jonathan Chung, Yishan Sun, Ricardo E. Dolmetsch, Kathleen A. Worringer, Robert J. Ihry
Summary: This study investigates the effects of CNVs in the 16p11.2 genomic region on neurodevelopmental phenotypes. By analyzing human cortical organoids, the researchers discover abnormal expression of neuronal-specific genes in patients with 16p11.2 deletion syndrome, and identify a new link between neuronal development and autism.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alessandro Gialluisi, Till F. M. Andlauer, Nazanin Mirza-Schreiber, Kristina Moll, Jessica Becker, Per Hoffmann, Kerstin U. Ludwig, Darina Czamara, Beate St Pourcain, Ferenc Honbolygo, Denes Toth, Valeria Csepe, Guillaume Huguet, Yves Chaix, Stephanie Iannuzzi, Jean-Francois Demonet, Andrew P. Morris, Jacqueline Hulslander, Erik G. Willcutt, John C. DeFries, Richard K. Olson, Shelley D. Smith, Bruce F. Pennington, Anniek Vaessen, Urs Maurer, Heikki Lyytinen, Myriam Peyrard-Janvid, Paavo H. T. Leppanen, Daniel Brandeis, Milene Bonte, John F. Stein, Joel B. Talcott, Fabien Fauchereau, Arndt Wilcke, Holger Kirsten, Bent Mueller, Clyde Francks, Thomas Bourgeron, Anthony P. Monaco, Franck Ramus, Karin Landerl, Juha Kere, Thomas S. Scerri, Silvia Paracchini, Simon E. Fisher, Johannes Schumacher, Markus M. Noethen, Bertram Mueller-Myhsok, Gerd Schulte-Koerne
Summary: This study highlights the significant contribution of common genetic variants to dyslexia risk, as well as novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Additionally, it revealed shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
MOLECULAR PSYCHIATRY
(2021)
Article
Behavioral Sciences
Chang Shu, LeeAnne Green Snyder, Yufeng Shen, Wendy K. Chung
Summary: The study developed machine learning models to predict cognitive impairment in children with autism, with the elastic-net model showing good performance using parent-reported data. This model provides a new evaluation method for large-scale autism studies when standardized cognitive testing is not feasible.
Article
Biochemistry & Molecular Biology
Anthony P. Monaco
Summary: This passage discusses the interaction and exchange between RNA pools in the environment and eukaryotic organisms, as well as the evolutionary history of RNA viruses shuttling between species. Horizontal transfer allows RNA pools to adapt for future interactions, leading to zoonotic transmission and detrimental RNA viral pandemics. Noncoding RNA (ncRNA) in eukaryotes serves as a mechanism to defend against viral attack and regulate host-derived mRNA. Transgenerational inheritance of ncRNA explains the "missing heritability" of common diseases. Causal graph theory and the Price Equation can model epigenetic inheritance involving dynamic RNA pools. Experimental designs should include metatranscriptomic analyses to understand ncRNA responses to changing environmental conditions across generations.
Article
Public, Environmental & Occupational Health
Alexandra M. Simas, Jimmy W. Crott, Chris Sedore, Augusta Rohrbach, Anthony P. Monaco, Stacey B. Gabriel, Niall Lennon, Brendan Blumenstiel, Caroline A. Genco
Summary: Repeated testing of a population is crucial for controlling the spread of the virus and reopening educational institutions safely. Pooling samples for analysis offers significant cost savings without compromising the specificity and sensitivity of the tests.
FRONTIERS IN PUBLIC HEALTH
(2021)
Article
Behavioral Sciences
Peter A. Perrino, Renee Y. Chasse, Anthony P. Monaco, Zoltan Molnar, Antonio Velayos-Baeza, R. Holly Fitch
Summary: Developmental dyslexia is a common neurodevelopmental disorder characterized by difficulties in reading and writing. The gene KIAA0319 has been identified as a candidate risk gene for dyslexia. Studies using animal models have shown inconsistent results, but recent experiments on KIAA0319 knockout mice revealed auditory processing impairments and neuroanatomical changes in relevant brain structures. These findings support a role for KIAA0319 in the development of auditory processing functions critical to speech processing, language, and reading.
GENES BRAIN AND BEHAVIOR
(2022)
Article
Psychiatry
Angela Tseng, Jazmin Camchong, Sunday M. Francis, Bryon A. Mueller, Kelvin O. Lim, Christine A. Conelea, Suma Jacob
Summary: This study used task-based functional connectivity MRI to examine emotion processing in ASD adolescents, revealing group differences in neural response and task performance, suggesting compensatory strategies in high-functioning ASD individuals.
JOURNAL OF PSYCHIATRIC RESEARCH
(2022)
Article
Psychiatry
Marta Viggiano, Tiziano D'Andrea, Cinzia Cameli, Annio Posar, Paola Visconti, Maria Cristina Scaduto, Roberta Colucci, Magali J. Rochat, Fabiola Ceroni, Giorgio Milazzo, Sergio Fucile, Elena Maestrini, Elena Bacchelli
Summary: Autism Spectrum Disorder (ASD) is a highly heterogeneous neuropsychiatric disorder with a strong genetic component. Voltage-gated calcium channels (VGCCs or Ca-v) genes, specifically the CACNA1H gene, have been identified as potential susceptibility genes for ASD. Through whole genome sequencing analysis, this study found rare damaging variants in Ca-v genes, including biallelic rare damaging missense variants in the CACNA1H gene, in ASD families. Electrophysiological analysis showed that these variants mildly affect calcium channel activity, potentially leading to dysregulation of intracellular calcium ions homeostasis and contributing to ASD etiology. These findings provide further evidence for the involvement of CACNA1H in neurodevelopmental disorders and suggest the importance of rare variants in ASD development.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Megan DuBois, Angela Tseng, Sunday M. Francis, Ann F. Haynos, Carol B. Peterson, Suma Jacob
Summary: This study measured OT levels in urine and plasma before and after intranasal delivery of synthetic OT. The results showed significantly higher levels of OT in urine and plasma after active compound delivery compared to placebo. Urine OT levels had larger effect sizes and more clearly differentiated pre-post levels compared to plasma OT levels. Urine OT levels may serve as an accessible and accurate systemic biomarker for evaluating OT dose-response and improving dosing for therapeutic goals.
Article
Genetics & Heredity
Suma Jacob, Evdokia Anagnostou, Eric Hollander, Roger Jou, Nora McNamara, Linmarie Sikich, Russell Tobe, Declan Murphy, James McCracken, Elizabeth Ashford, Christopher Chatham, Susanne Clinch, Janice Smith, Kevin Sanders, Lorraine Murtagh, Jana Noeldeke, Jeremy Veenstra-VanderWeele
Summary: This article discusses the challenges faced by autism spectrum disorder treatment research, highlighting the placebo response in treatment trials and its association with baseline symptom severity, recruitment methods, and trial site experience.
Article
Genetics & Heredity
Xueya Zhou, Pamela Feliciano, Chang Shu, Tianyun Wang, Irina Astrovskaya, Jacob B. Hall, Joseph U. Obiajulu, Jessica R. Wright, Shwetha C. Murali, Simon Xuming Xu, Leo Brueggeman, Taylor R. Thomas, Olena Marchenko, Christopher Fleisch, Sarah D. Barns, LeeAnne Green Snyder, Bing Han, Timothy S. Chang, Tychele N. Turner, William T. Harvey, Andrew Nishida, Brian J. O'Roak, Daniel H. Geschwind, Jacob J. Michaelson, Natalia Volfovsky, Evan E. Eichler, Yufeng Shen, Wendy K. Chung
Summary: In a comprehensive analysis of autism cases, we identified 60 genes, including five new risk genes, that are significantly associated with autism risk. The NAV3 gene is primarily associated with autism risk through rare inherited variants and has a moderate effect. Autistic individuals with moderate-risk genes show less cognitive impairment compared to those with highly penetrant genes.
Article
Multidisciplinary Sciences
Tianyun Wang, Chang N. Kim, Trygve E. Bakken, Madelyn A. Gillentine, Barbara Henning, Yafei Mao, Christian Gilissen, Tomasz J. Nowakowski, Evan E. Eichler
Summary: This study identifies 615 candidate genes associated with neurodevelopmental disorders (NDDs), grouping them into five functional networks based on single-cell nuclei transcriptomic data. There is no evidence for ASD-specific genes, but 18 genes significantly enriched for developmental disorders (DD) are found. Mutational bias is observed in 53 genes, including enrichments for missense or truncating genetic variants. There are also 10 genes that show evidence of sex-biased enrichment, including 4 X chromosome genes with significant female burden.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Samuel T. Nemanich, Daniel H. Lench, Ellen N. Sutter, Jesse L. Kowalski, Sunday M. Francis, Gregg D. Meekins, Linda E. Krach, Tim Feyma, Bernadette T. Gillick
Summary: Children with hemiparesis (CWH) due to stroke early in life may benefit from transcranial direct current stimulation (tDCS) as an adjuvant therapy to enhance rehabilitation. Tailored protocols of tDCS based on individual corticospinal tract organization are necessary to achieve optimal outcomes. This study evaluated the safety, feasibility, and preliminary effects of targeted anodal tDCS on corticospinal excitability in CWH.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2023)
Editorial Material
Behavioral Sciences
Lindsay M. Oberman, Sunday M. Francis, Sarah H. Lisanby
Summary: Noninvasive brain stimulation (NIBS) techniques, such as rTMS and tDCS, are emerging as alternative interventions for psychiatric, neurological, and neurodevelopmental conditions. However, the safety and efficacy of using NIBS in children with ASD is limited, and larger randomized controlled trials are needed to evaluate its potential.
Article
Psychology, Developmental
L. Casey White, J. Kiely Law, Amy M. Daniels, Jaimie Toroney, Brianna Vernoia, Sabrina Xiao, Pamela Feliciano, Wendy K. Chung
Summary: The impact of the COVID-19 pandemic on the autism community in the United States is unprecedented, leading to significant disruptions in therapies, especially for children under age five. Caregivers also reported worsening ASD symptoms and moderate family distress. Strategies to support the ASD community should be developed and implemented immediately.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2021)
Article
Psychology, Developmental
Colleen M. Doyle, Carolyn Lasch, Elayne P. Vollman, Christopher D. Desjardins, Nathaniel E. Helwig, Suma Jacob, Jason J. Wolff, Jed T. Elison
Summary: This study identified five subgroups of toddlers through factor mixture modeling, with high- and moderate-risk groups comprising 6% of the sample. The utility of risk profile classification was supported by different outcomes across the high-, moderate-, and low-risk groups, with large effect sizes for internalizing, externalizing, and dysregulation differences between high- and low-risk groups. Data-driven approaches show promise for early identification of at-risk-phenotypes for various early emerging neurodevelopmental disorders.
JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
(2021)