Articles

Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP

Mutations in TSC2 are the most common cause of tuberous sclerosis (TSC), a disorder with a high incidence of autism and intellectual disability. TSC2 regulates mRNA translation required for group 1 metabotropic g...

Authors: Annie Hien, Gemma Molinaro, Botao Liu, Kimberly M. Huber and Joel D. Richter

De novo missense variants disrupting protein–protein interactions affect risk for autism through gene co-expression and protein networks in neuronal cell types

Whole-exome sequencing studies have been useful for identifying genes that, when mutated, affect risk for autism spectrum disorder (ASD). Nonetheless, the association signal primarily arises from de novo prote...

Authors: Siwei Chen, Jiebiao Wang, Ercument Cicek, Kathryn Roeder, Haiyuan Yu and Bernie Devlin

Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder

Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically ...

Authors: Lin Wang, Yi Zhang, Kuokuo Li, Zheng Wang, Xiaomeng Wang, Bin Li, Guihu Zhao, Zhenghuan Fang, Zhengbao Ling, Tengfei Luo, Lu Xia, Yanping Li, Hui Guo, Zhengmao Hu, Jinchen Li, Zhongsheng Sun…

Chd8 haploinsufficiency impairs early brain development and protein homeostasis later in life

Chromodomain helicase DNA-binding protein 8 (Chd8) is a high-confidence risk gene for autism spectrum disorder (ASD). However, how Chd8 haploinsufficiency impairs gene expression in the brain and impacts behavior...

Authors: Jessica A. Jiménez, Travis S. Ptacek, Alex H. Tuttle, Ralf S. Schmid, Sheryl S. Moy, Jeremy M. Simon and Mark J. Zylka

Autistic traits, systemising, empathising, and theory of mind in transgender and non-binary adults

Prior research examining autistic traits in gender minority adults has reported mixed findings. Most prior studies did not include non-binary individuals. Little is known about the mechanisms shaping autistic ...

Authors: Karson T. F. Kung

Differential mirror neuron system (MNS) activation during action observation with and without social-emotional components in autism: a meta-analysis of neuroimaging studies

Impaired imitation has been found to be an important factor contributing to social communication deficits in individuals with autism spectrum disorder (ASD). It has been hypothesized that the neural correlate ...

Authors: Melody M. Y. Chan and Yvonne M. Y. Han

Enhanced social learning of threat in adults with autism

Recent theories have linked autism to challenges in prediction learning and social cognition. It is unknown, however, how autism affects learning about threats from others “demonstrators” through observation, ...

Authors: Lisa Espinosa, Johan Lundin Kleberg, Björn Hofvander, Steve Berggren, Sven Bölte and Andreas Olsson

Assessing the requirements of prenatal UBE3A expression for rescue of behavioral phenotypes in a mouse model for Angelman syndrome

Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of functional ubiquitin protein ligase E3A (UBE3A). In neurons, UBE3A expression is tightly regulated by a mechanism of imprintin...

Authors: Monica Sonzogni, Peipei Zhai, Edwin J. Mientjes, Geeske M. van Woerden and Ype Elgersma

Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology

The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective b...

Authors: Cristina Cheroni, Nicolò Caporale and Giuseppe Testa

Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms

Several genetic alterations, including point mutations and copy number variations in NLGN genes, have been associated with psychiatric disorders, such as autism spectrum disorder (ASD) and X-linked mental retarda...

Authors: Takafumi Yumoto, Misaki Kimura, Ryota Nagatomo, Tsukika Sato, Shun Utsunomiya, Natsue Aoki, Motoji Kitaura, Koji Takahashi, Hiroshi Takemoto, Hirotaka Watanabe, Hideyuki Okano, Fumiaki Yoshida, Yosuke Nao and Taisuke Tomita

Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach

Heterogeneity in the phenotypic presentation of autism spectrum disorder (ASD) is apparent in the profile and the severity of sensory features. Here, we applied factor mixture modelling (FMM) to test a multidi...

Authors: J. Tillmann, M. Uljarevic, D. Crawley, G. Dumas, E. Loth, D. Murphy, J. Buitelaar and T. Charman

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis

Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms.

Authors: Spyridon Siafis, Oğulcan Çıray, Johannes Schneider-Thoma, Irene Bighelli, Marc Krause, Alessandro Rodolico, Anna Ceraso, Giacomo Deste, Maximilian Huhn, David Fraguas, Dimitris Mavridis, Tony Charman, Declan G. Murphy, Mara Parellada, Celso Arango and Stefan Leucht

Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mouse model of autism Shank3B

Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan–McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there ...

Authors: N. Perets, O. Oron, S. Herman, E. Elliott and D. Offen

The sociability spectrum: evidence from reciprocal genetic copy number variations

Sociability entails some of the most complex behaviors processed by the central nervous system. It includes the detection, integration, and interpretation of social cues and elaboration of context-specific res...

Authors: Alejandro López-Tobón, Sebastiano Trattaro and Giuseppe Testa

Development of the Signposting Questionnaire for Autism (SQ-A): measurement comparison with the 10-item Autism Spectrum Quotient-Child and the Strengths and Difficulties Questionnaire in the UK and Latvia

Recognising the signs of autism spectrum disorder (ASD) can be a challenge for frontline professionals. The use of brief parent-completed questionnaires for recording the signs of ASD in school-aged children m...

Authors: Catherine R. G. Jones, Sarah L. Barrett, Ieva Bite, Maria Legzdina, Kristina Arina, Andrea Higgins, Kyla Honey, Sarah J. Carrington, Dale Hay, Johanna Condon and Susan R. Leekam

Alexithymia may explain the relationship between autistic traits and eating disorder psychopathology

Autistic people are disproportionately vulnerable to anorexia nervosa and other eating disorders (ED), and within the general population, autistic traits correlate with ED psychopathology. A putative mechanism...

Authors: L. Vuillier, Z. Carter, A. R. Teixeira and R. L. Moseley

Targeting PPARα in the rat valproic acid model of autism: focus on social motivational impairment and sex-related differences

The social motivational theory of autism spectrum disorder (ASD) focuses on social anhedonia as key causal feature of the impaired peer relationships that characterize ASD patients. ASD prevalence is higher in...

Authors: Simona Scheggi, Francesca Guzzi, Giulia Braccagni, Maria Graziella De Montis, Marco Parenti and Carla Gambarana

Coping, fostering resilience, and driving care innovation for autistic people and their families during the COVID-19 pandemic and beyond

The new coronavirus disease (COVID-19) pandemic is changing how society operates. Environmental changes, disrupted routines, and reduced access to services and social networks will have a unique impact on auti...

Authors: Stephanie H. Ameis, Meng-Chuan Lai, Benoit H. Mulsant and Peter Szatmari

Does decreased visual attention to faces underlie difficulties interpreting eye gaze cues in autism?

Shifts in eye gaze communicate social information that allows people to respond to another’s behavior, interpret motivations driving behavior, and anticipate subsequent behavior. Understanding the social commu...

Authors: Jason W. Griffin and K. Suzanne Scherf

Empathic disequilibrium in two different measures of empathy predicts autism traits in neurotypical population

Features of autism spectrum conditions (ASC) are normally distributed within the population, giving rise to the notion of the autism spectrum. One of the hallmark features of ASC is difficulties in social comm...

Authors: Ido Shalev and Florina Uzefovsky

Cerebral organoids as tools to identify the developmental roots of autism

Some autism spectrum disorders (ASD) likely arise as a result of abnormalities during early embryonic development of the brain. Studying human embryonic brain development directly is challenging, mainly due to...

Authors: Wai Kit Chan, Rosie Griffiths, David J. Price and John O. Mason

Gender identity, sexual orientation and adverse sexual experiences in autistic females

There is growing recognition that autistic females present with more diverse gender and sexual identities than their non-autistic counterparts. Likewise, autistic females are also at an increased risk of adver...

Authors: Laura A. Pecora, Grace I. Hancock, Merrilyn Hooley, David H. Demmer, Tony Attwood, Gary B. Mesibov and Mark A. Stokes

Reduced auditory steady state responses in autism spectrum disorder

Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in A...

Authors: R. A. Seymour, G. Rippon, G. Gooding-Williams, P. F. Sowman and K. Kessler

IGF-1 treatment causes unique transcriptional response in neurons from individuals with idiopathic autism

Research evidence accumulated in the past years in both rodent and human models for autism spectrum disorders (ASD) have established insulin-like growth factor 1 (IGF-1) as one of the most promising ASD therap...

Authors: Sara B. Linker, Ana P. D. Mendes and Maria C. Marchetto

Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study

Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show tha...

Authors: Axel Krug, Markus Wöhr, Dominik Seffer, Henrike Rippberger, A. Özge Sungur, Bruno Dietsche, Frederike Stein, Sugirthan Sivalingam, Andreas J. Forstner, Stephanie H. Witt, Helene Dukal, Fabian Streit, Anna Maaser, Stefanie Heilmann-Heimbach, Till F. M. Andlauer, Stefan Herms…

Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism

Phelan-McDermid syndrome (PMS) is a rare genetic disorder with high risk of autism spectrum disorder (ASD), intellectual disability, and language delay, and is caused by 22q13.3 deletions or mutations in the SHAN...

Authors: Michael S. Breen, Andrew Browne, Gabriel E. Hoffman, Sofia Stathopoulos, Kristen Brennand, Joseph D. Buxbaum and Elodie Drapeau

Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns

Fragile X syndrome (FXS), a neurodevelopmental disorder, is a leading monogenetic cause of intellectual disability and autism spectrum disorder. Notwithstanding the extensive studies using rodent and other pre...

Authors: Shreya Das Sharma, Rakhi Pal, Bharath Kumar Reddy, Bhuvaneish T. Selvaraj, Nisha Raj, Krishna Kumar Samaga, Durga J. Srinivasan, Loren Ornelas, Dhruv Sareen, Matthew R. Livesey, Gary J. Bassell, Clive N. Svendsen, Peter C. Kind, Siddharthan Chandran, Sumantra Chattarji and David J. A. Wyllie

Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism

The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growt...

Authors: Lisa D. Yankowitz, John D. Herrington, Benjamin E. Yerys, Joseph A. Pereira, Juhi Pandey and Robert T. Schultz

Sex differences in the first impressions made by girls and boys with autism

Individuals with autism spectrum disorder (ASD) are characterized by social communication challenges and repetitive behaviors that may be quickly detected by experts (Autism Res 10:653–62, 2017; American Psych...

Authors: Meredith L. Cola, Samantha Plate, Lisa Yankowitz, Victoria Petrulla, Leila Bateman, Casey J. Zampella, Ashley de Marchena, Juhi Pandey, Robert T. Schultz and Julia Parish-Morris

Defining clusters of young autistic and typically developing children based on loudness-dependent auditory electrophysiological responses

Autistic individuals exhibit atypical patterns of sensory processing that are known to be related to quality of life, but which are also highly heterogeneous. Previous investigations of this heterogeneity have...

Authors: Patrick Dwyer, Xiaodong Wang, Rosanna De Meo-Monteil, Fushing Hsieh, Clifford D. Saron and Susan M. Rivera

Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes

In fast firing, parvalbumin (PV)-expressing (Pvalb) interneurons, PV acts as an intracellular Ca²⁺ signal modulator with slow-onset kinetics. In Purkinje cells of PV^−/− mice, adaptive/homeostatic mechanisms lead ...

Authors: Lucia Janickova, Karin Farah Rechberger, Lucas Wey and Beat Schwaller

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 deletion synd...

Authors: Maria Gudbrandsen, Anke Bletsch, Caroline Mann, Eileen Daly, Clodagh M. Murphy, Vladimira Stoencheva, Charlotte E. Blackmore, Maria Rogdaki, Leila Kushan, Carrie E. Bearden, Declan G. M. Murphy, Michael C. Craig and Christine Ecker

Transcriptional consequences of MBD5 disruption in mouse brain and CRISPR-derived neurons

MBD5, encoding the methyl-CpG-binding domain 5 protein, has been proposed as a necessary and sufficient driver of the 2q23.1 microdeletion syndrome. De novo missense and protein-truncating variants from exome seq...

Authors: Catarina M. Seabra, Tatsiana Aneichyk, Serkan Erdin, Derek J. C. Tai, Celine E. F. De Esch, Parisa Razaz, Yu An, Poornima Manavalan, Ashok Ragavendran, Alexei Stortchevoi, Clemer Abad, Juan I. Young, Patricia Maciel, Michael E. Talkowski and James F. Gusella

Electronic communication in autism spectrum conditions

Authors: Lucy Anne Livingston, Chris Ashwin and Punit Shah

Decreased nuclear Pten in neural stem cells contributes to deficits in neuronal maturation

PTEN, a syndromic autism spectrum disorder (ASD) risk gene, is mutated in approximately 10% of macrocephalic ASD cases. Despite the described genetic association between PTEN and ASD and ensuing studies, we conti...

Authors: Shin Chung Kang, Ritika Jaini, Masahiro Hitomi, Hyunpil Lee, Nick Sarn, Stetson Thacker and Charis Eng

Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD

Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype...

Authors: Danijela Drakulic, Srdjan Djurovic, Yasir Ahmed Syed, Sebastiano Trattaro, Nicolò Caporale, Anna Falk, Rivka Ofir, Vivi M. Heine, Samuel J. R. A. Chawner, Antonio Rodriguez-Moreno, Marianne B. M. van den Bree, Giuseppe Testa, Spyros Petrakis and Adrian J. Harwood

Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment

FXS is the most common genetic cause of intellectual (ID) and autism spectrum disorders (ASD). FXS is caused by loss of FMRP, an RNA-binding protein involved in the translational regulation of a large number o...

Authors: Kagistia Hana Utami, Nur Amirah Binte Mohammad Yusof, Jing Eugene Kwa, Ulla-Kaisa Peteri, Maija L. Castrén and Mahmoud A. Pouladi

Dysregulation of protein synthesis and dendritic spine morphogenesis in ASD: studies in human pluripotent stem cells

Autism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgeni...

Authors: Louisa Hoi-Ying Lo and Kwok-On Lai

Identification of amygdala-expressed genes associated with autism spectrum disorder

Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a...

Authors: Maria Jesus Herrero, Dmitry Velmeshev, David Hernandez-Pineda, Saarthak Sethi, Shawn Sorrells, Payal Banerjee, Catherine Sullivan, Abha R. Gupta, Arnold R. Kriegstein and Joshua G. Corbin

Quantitative proteomic analysis of Rett iPSC-derived neuronal progenitors

Rett syndrome (RTT) is a progressive neurodevelopmental disease that is characterized by abnormalities in cognitive, social, and motor skills. RTT is often caused by mutations in the X-linked gene encoding met...

Authors: Suzy Varderidou-Minasian, Lisa Hinz, Dominique Hagemans, Danielle Posthuma, Maarten Altelaar and Vivi M. Heine

Cell therapy approaches to autism: a review of clinical trial data

A number of clinical trials of cell therapies for autism spectrum disorder have been conducted, and some have published their outcomes. This review considers the data that have emerged from this small set of p...

Authors: Jack Price

Age-related differences in white matter diffusion measures in autism spectrum condition

Autism spectrum condition (ASC) is accompanied by developmental differences in brain anatomy and connectivity. White matter differences in ASC have been widely studied with diffusion imaging but results are he...

Authors: Abigail Thompson, Asal Shahidiani, Anne Fritz, Jonathan O’Muircheartaigh, Lindsay Walker, Vera D’Almeida, Clodagh Murphy, Eileen Daly, Declan Murphy, Steve Williams, Sean Deoni and Christine Ecker

Prevalence and cumulative incidence of autism spectrum disorders and the patterns of co-occurring neurodevelopmental disorders in a total population sample of 5-year-old children

Whether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has n...

Authors: Manabu Saito, Tomoya Hirota, Yui Sakamoto, Masaki Adachi, Michio Takahashi, Ayako Osato-Kaneda, Young Shin Kim, Bennett Leventhal, Amy Shui, Sumi Kato and Kazuhiko Nakamura

Effectiveness of a modified group cognitive behavioral therapy program for anxiety in children with ASD delivered in a community context

Youth with autism spectrum disorder (ASD) experience high rates (approximately 50–79%) of comorbid anxiety problems. Given the significant interference and distress that excessive anxiety can cause, evidence-b...

Authors: Abbie Solish, Nora Klemencic, Anne Ritzema, Vicki Nolan, Martha Pilkington, Evdokia Anagnostou and Jessica Brian

Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells

Genetic factors contribute to the development of autism spectrum disorder (ASD), and although non-protein-coding regions of the genome are being increasingly implicated in ASD, the functional consequences of t...

Authors: P. Joel Ross, Rebecca S. F. Mok, Brandon S. Smith, Deivid C. Rodrigues, Marat Mufteev, Stephen W. Scherer and James Ellis

Exploring the mechanisms underlying excitation/inhibition imbalance in human iPSC-derived models of ASD

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders characterized by impaired social interaction and communication, and repetitive or restricted behaviors. ASD subjects exhibit complex ge...

Authors: Lorenza Culotta and Peter Penzes

Automated recognition of spontaneous facial expression in individuals with autism spectrum disorder: parsing response variability

Reduction or differences in facial expression are a core diagnostic feature of autism spectrum disorder (ASD), yet evidence regarding the extent of this discrepancy is limited and inconsistent. Use of automate...

Authors: Abigail Bangerter, Meenakshi Chatterjee, Joseph Manfredonia, Nikolay V. Manyakov, Seth Ness, Matthew A. Boice, Andrew Skalkin, Matthew S. Goodwin, Geraldine Dawson, Robert Hendren, Bennett Leventhal, Frederick Shic and Gahan Pandina

Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study

Tuberous sclerosis complex (TSC) is an autosomal dominant disease that affects multiple organs including the brain. TSC is strongly associated with broad neurodevelopmental disorders, including autism spectrum...

Authors: Dorinde M. van Andel, Jan J. Sprengers, Bob Oranje, Floortje E. Scheepers, Floor E. Jansen and Hilgo Bruining

Tsc1 haploinsufficiency in Nkx2.1 cells upregulates hippocampal interneuron mTORC1 activity, impairs pyramidal cell synaptic inhibition, and alters contextual fear discrimination and spatial working memory in mice

Mutations in TSC1 or TSC2 genes cause tuberous sclerosis complex (TSC), a disorder associated with epilepsy, autism, and intellectual disability. TSC1 and TSC2 are repressors of the mechanistic target of rapamyci...

Authors: Nabila Haji, Ilse Riebe, Argel Aguilar-Valles, Julien Artinian, Isabel Laplante and Jean-Claude Lacaille

Inattention and hyperactive/impulsive component scores do not differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder in a clinical sample

Although there is high co-occurrence between ASD and ADHD, the nature of this co-occurrence remains unclear. Our study aimed to examine the underlying relationship between ASD and ADHD symptoms in a combined s...

Authors: Aneta D. Krakowski, Katherine Tombeau Cost, Evdokia Anagnostou, Meng-Chuan Lai, Jennifer Crosbie, Russell Schachar, Stelios Georgiades, Eric Duku and Peter Szatmari