Articles

Arbaclofen in fragile X syndrome: results of phase 3 trials

Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and eff...

Authors: Elizabeth Berry-Kravis, Randi Hagerman, Jeannie Visootsak, Dejan Budimirovic, Walter E. Kaufmann, Maryann Cherubini, Peter Zarevics, Karen Walton-Bowen, Paul Wang, Mark F. Bear and Randall L. Carpenter

Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety

Fragile X Syndrome (FXS) occurs as a result of a silenced fragile X mental retardation 1 gene (FMR1) and subsequent loss of fragile X mental retardation protein (FMRP) expression. Loss of FMRP alters excitatory/i...

Authors: Tori L. Schaefer, Matthew H. Davenport, Lindsay M. Grainger, Chandler K. Robinson, Anthony T. Earnheart, Melinda S. Stegman, Anna L. Lang, Amy A. Ashworth, Gemma Molinaro, Kimberly M. Huber and Craig A. Erickson

Updated report on tools to measure outcomes of clinical trials in fragile X syndrome

Fragile X syndrome (FXS) has been the neurodevelopmental disorder with the most active translation of preclinical breakthroughs into clinical trials. This process has led to a critical assessment of outcome me...

Authors: Dejan B. Budimirovic, Elizabeth Berry-Kravis, Craig A. Erickson, Scott S. Hall, David Hessl, Allan L. Reiss, Margaret K. King, Leonard Abbeduto and Walter E. Kaufmann

Fragile X targeted pharmacotherapy: lessons learned and future directions

Our understanding of fragile X syndrome (FXS) pathophysiology continues to improve and numerous potential drug targets have been identified. Yet, current prescribing practices are only symptom-based in order t...

Authors: Craig A. Erickson, Matthew H. Davenport, Tori L. Schaefer, Logan K. Wink, Ernest V. Pedapati, John A. Sweeney, Sarah E. Fitzpatrick, W. Ted Brown, Dejan Budimirovic, Randi J. Hagerman, David Hessl, Walter E. Kaufmann and Elizabeth Berry-Kravis

Diagnoses and characteristics of autism spectrum disorders in children with Prader-Willi syndrome

A small percentage of people with autism spectrum disorders (ASD) have alterations in chromosome 15q11.2-q3, the critical region for Prader-Willi syndrome (PWS). Data are limited, however, on the rates and cha...

Authors: Elisabeth M. Dykens, Elizabeth Roof, Hailee Hunt-Hawkins, Nathan Dankner, Evon Batey Lee, Carolyn M. Shivers, Christopher Daniell and Soo-Jeong Kim

Exploring the heterogeneity of neural social indices for genetically distinct etiologies of autism

Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to speci...

Authors: Caitlin M. Hudac, Holly A. F. Stessman, Trent D. DesChamps, Anna Kresse, Susan Faja, Emily Neuhaus, Sara Jane Webb, Evan E. Eichler and Raphael A. Bernier

Motor problems in children with neurofibromatosis type 1

Children with the neurogenetic disorder neurofibromatosis type 1 (NF1) often have problems with learning and behaviour. In both parent reports and neuropsychological assessment, motor problems are reported in ...

Authors: André B. Rietman, Rianne Oostenbrink, Sanne Bongers, Eddy Gaukema, Sandra van Abeelen, Jos G. Hendriksen, Caspar W. N. Looman, Pieter F. A. de Nijs and Marie-Claire de Wit

Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis

Clinicians have qualitatively described rhythmic delta activity as a prominent EEG abnormality in individuals with Angelman syndrome, but this phenotype has yet to be rigorously quantified in the clinical popu...

Authors: Michael S. Sidorov, Gina M. Deck, Marjan Dolatshahi, Ronald L. Thibert, Lynne M. Bird, Catherine J. Chu and Benjamin D. Philpot

Reduced vagal tone in women with the FMR1 premutation is associated with FMR1 mRNA but not depression or anxiety

Autonomic dysfunction is implicated in a range of psychological conditions, including depression and anxiety. The fragile X mental retardation-1 (FMR1) premutation is a common genetic mutation that affects ~1:150...

Authors: Jessica Klusek, Giuseppe LaFauci, Tatyana Adayev, W. Ted Brown, Flora Tassone and Jane E. Roberts

Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study

Rett syndrome is a severe neurodevelopmental disorder associated with mutations in the MECP2 gene. Irregular breathing patterns and abdominal bloating are prominent but poorly understood features. Our aims were t...

Authors: Jessica Mackay, Jenny Downs, Kingsley Wong, Jane Heyworth, Amy Epstein and Helen Leonard

Atypical sound discrimination in children with ASD as indicated by cortical ERPs

Individuals with autism spectrum disorder (ASD) show a relative indifference to the human voice. Accordingly, and contrarily to their typically developed peers, adults with autism do not show a preferential re...

Authors: Aurélie Bidet-Caulet, Marianne Latinus, Sylvie Roux, Joëlle Malvy, Frédérique Bonnet-Brilhault and Nicole Bruneau

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome

Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of a...

Authors: Jun Wang, Lauren E. Ethridge, Matthew W. Mosconi, Stormi P. White, Devin K. Binder, Ernest V. Pedapati, Craig A. Erickson, Matthew J. Byerly and John A. Sweeney

Erratum to: A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome

Authors: Michelle Lee, Gary E. Martin, Elizabeth Berry-Kravis and Molly Losh

Preserved search asymmetry in the detection of fearful faces among neutral faces in individuals with Williams syndrome revealed by measurement of both manual responses and eye tracking

Individuals with Williams syndrome (WS) exhibit an atypical social phenotype termed hypersociability. One theory accounting for hypersociability presumes an atypical function of the amygdala, which processes f...

Authors: Masahiro Hirai, Yukako Muramatsu, Seiji Mizuno, Naoko Kurahashi, Hirokazu Kurahashi and Miho Nakamura

Altered functional resting-state hypothalamic connectivity and abnormal pituitary morphology in children with Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder, characterized by endocrine problems and hyperphagia, indicating hypothalamic-pituitary dysfunction. However, few studies have explored the ...

Authors: Akvile Lukoshe, Suzanne E. van Dijk, Gerbrich E. van den Bosch, Aad van der Lugt, Tonya White and Anita C. Hokken-Koelega

Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families

It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investiga...

Authors: M. Woodbury-Smith, D. A. Bilder, J. Morgan, L. Jerominski, T. Darlington, T. Dyer, A. D. Paterson and H. Coon

Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder

Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemisphe...

Authors: Kayla H. Finch, Anne M. Seery, Meagan R. Talbott, Charles A. Nelson and Helen Tager-Flusberg

Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas

Autism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic muta...

Authors: Leah B. Townsend and Spencer L. Smith

Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder

Disruptive behavior in autism spectrum disorder (ASD) is an important clinical problem, but its neural basis remains poorly understood. The current research aims to better understand the neural underpinnings o...

Authors: Y. J. Daniel Yang, Denis G. Sukhodolsky, Jiedi Lei, Eran Dayan, Kevin A. Pelphrey and Pamela Ventola

A developmental, longitudinal investigation of autism phenotypic profiles in fragile X syndrome

Targeting overlapping behavioral phenotypes in neurogenetic disorders can help elucidate gene-behavior relationships. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) have been studied as a model fo...

Authors: Michelle Lee, Gary E. Martin, Elizabeth Berry-Kravis and Molly Losh

Verbal labels increase the salience of novel objects for preschoolers with typical development and Williams syndrome, but not in autism

Early research has documented that young children show an increased interest toward objects that are verbally labeled by an adult, compared to objects that are presented without a label. It is unclear whether ...

Authors: Giacomo Vivanti, Darren R. Hocking, Peter Fanning and Cheryl Dissanayake

Wnt signaling networks in autism spectrum disorder and intellectual disability

Genetic factors play a major role in the risk for neurodevelopmental disorders such as autism spectrum disorders (ASDs) and intellectual disability (ID). The underlying genetic factors have become better under...

Authors: Vickie Kwan, Brianna K. Unda and Karun K. Singh

Functional characterization of rare FOXP2 variants in neurodevelopmental disorder

Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-alte...

Authors: Sara B. Estruch, Sarah A. Graham, Swathi M. Chinnappa, Pelagia Deriziotis and Simon E. Fisher

Postural orientation and equilibrium processes associated with increased postural sway in autism spectrum disorder (ASD)

Increased postural sway has been repeatedly documented in children with autism spectrum disorder (ASD). Characterizing the control processes underlying this deficit, including postural orientation and equilibr...

Authors: Zheng Wang, Rami R. Hallac, Kaitlin C. Conroy, Stormi P. White, Alex A. Kane, Amy L. Collinsworth, John A. Sweeney and Matthew W. Mosconi

Associations between social cognition, skills, and function and subclinical negative and positive symptoms in 22q11.2 deletion syndrome

Identification of the early signs of schizophrenia would be a major achievement for the early intervention and prevention strategies in psychiatry. Social impairments are defining features of schizophrenia. Im...

Authors: A. Vangkilde, J. R. M. Jepsen, H. Schmock, C. Olesen, S. Arnarsdóttir, W. F. C. Baaré, K. J. Plessen, M. Didriksen, H. R. Siebner, T. Werge and L. Olsen

Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study

Children affected by the 22q11.2 deletion syndrome (22q11.2DS) have a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown t...

Authors: Mathilde Bostelmann, Maude Schneider, Maria Carmela Padula, Johanna Maeder, Marie Schaer, Elisa Scariati, Martin Debbané, Bronwyn Glaser, Sarah Menghetti and Stephan Eliez

Developmental profiles of infants with an FMR1 premutation

Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the e...

Authors: Anne C. Wheeler, John Sideris, Randi Hagerman, Elizabeth Berry-Kravis, Flora Tassone and Donald B. Bailey Jr.

Typical visual search performance and atypical gaze behaviors in response to faces in Williams syndrome

Evidence indicates that individuals with Williams syndrome (WS) exhibit atypical attentional characteristics when viewing faces. However, the dynamics of visual attention captured by faces remain unclear, espe...

Authors: Masahiro Hirai, Yukako Muramatsu, Seiji Mizuno, Naoko Kurahashi, Hirokazu Kurahashi and Miho Nakamura

Erratum to: Long-term alterations of striatal parvalbumin interneurons in a rat model of early exposure to alcohol

Authors: Andrea De Giorgio, Sara E. Comparini, Francesca Sangiuliano Intra and Alberto Granato

Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome

Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by disruptions in the MECP2 gene. MECP2-null mice show imbalances in neuronal excitability and synaptic communications. Several previous studies ...

Authors: Weiwei Zhong, Christopher Mychal Johnson, Yang Wu, Ningren Cui, Hao Xing, Shuang Zhang and Chun Jiang

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit differ...

Authors: Matthew J. Gazzellone, Mehdi Zarrei, Christie L. Burton, Susan Walker, Mohammed Uddin, S. M. Shaheen, Julie Coste, Rageen Rajendram, Reva J. Schachter, Marlena Colasanto, Gregory L. Hanna, David R. Rosenberg, Noam Soreni, Kate D. Fitzgerald, Christian R. Marshall, Janet A. Buchanan…

The NIH Toolbox Cognitive Battery for intellectual disabilities: three preliminary studies and future directions

Recent advances in understanding molecular and synaptic mechanisms of intellectual disabilities (ID) in fragile X syndrome (FXS) and Down syndrome (DS) through animal models have led to targeted controlled tri...

Authors: David Hessl, Stephanie M. Sansone, Elizabeth Berry-Kravis, Karen Riley, Keith F. Widaman, Leonard Abbeduto, Andrea Schneider, Jeanine Coleman, Dena Oaklander, Kelly C. Rhodes and Richard C. Gershon

Atypical audiovisual word processing in school-age children with a history of specific language impairment: an event-related potential study

Visual speech cues influence different aspects of language acquisition. However, whether developmental language disorders may be associated with atypical processing of visual speech is unknown. In this study, ...

Authors: Natalya Kaganovich, Jennifer Schumaker and Courtney Rowland

Automatic cortical representation of auditory pitch changes in Rett syndrome

Over the typical course of Rett syndrome, initial language and communication abilities deteriorate dramatically between the ages of 1 and 4 years, and a majority of these children go on to lose all oral commun...

Authors: John J. Foxe, Kelly M. Burke, Gizely N. Andrade, Aleksandra Djukic, Hans-Peter Frey and Sophie Molholm

Comparing oxytocin and cortisol regulation in a double-blind, placebo-controlled, hydrocortisone challenge pilot study in children with autism and typical development

Children with autism spectrum disorder (ASD) show marked impairment in social functioning and poor adaptation to new and changing contexts, which may be influenced by underlying regulatory processes. Oxytocin ...

Authors: Blythe A. Corbett, Karen L. Bales, Deanna Swain, Kevin Sanders, Tamara A. R. Weinstein and Louis J. Muglia

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition

People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may p...

Authors: Kathryn L. McCabe, Stuart Marlin, Gavin Cooper, Robin Morris, Ulrich Schall, Declan G. Murphy, Kieran C. Murphy and Linda E. Campbell

Neurophysiological hyperresponsivity to sensory input in autism spectrum disorders

Atypical sensory processing is a common clinical observation in autism spectrum disorder (ASD). Neural hyperexcitability has been suggested as the cause for sensory hypersensitivity, a frequently reported clin...

Authors: Yukari Takarae, Savanna R. Sablich, Stormi P. White and John A. Sweeney

Erratum to: Neural correlates of reward processing in adults with 22q11 deletion syndrome

Authors: Esther D. A. Van Duin, Liesbet Goossens, Dennis Hernaus, Fabiana Da Silva Alves, Nicole Schmitz, Koen Schruers and Therese Van Amelsvoort

A quantitative measure of restricted and repetitive behaviors for early childhood

Restricted and repetitive behaviors are characteristic phenotypic features of many neurodevelopmental, psychiatric, and neurological conditions. During early childhood, such behaviors are considered normative....

Authors: Jason J. Wolff, Brian A. Boyd and Jed T. Elison

Cumulative life events, traumatic experiences, and psychiatric symptomatology in transition-aged youth with autism spectrum disorder

Co-occurring mood and anxiety symptomatology is commonly observed among youth with autism spectrum disorders (ASD) during adolescence and adulthood. Yet, little is known about the factors that might predispose...

Authors: Julie Lounds Taylor and Katherine O. Gotham

Sex bias in autism spectrum disorder in neurofibromatosis type 1

Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis ty...

Authors: Shruti Garg, Hein Heuvelman, Susan Huson, Hannah Tobin and Jonathan Green

Neural correlates of reward processing in adults with 22q11 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is lo...

Authors: Esther D. A. van Duin, Liesbet Goossens, Dennis Hernaus, Fabiana da Silva Alves, Nicole Schmitz, Koen Schruers and Therese van Amelsvoort

Characterization of Rett Syndrome-like phenotypes in Mecp2-knockout rats

Rett Syndrome (RTT) is a neurodevelopmental disease caused by the disruption of the MECP2 gene. Several mouse models of RTT have been developed with Mecp2 disruptions. Although the mouse models are widely used in...

Authors: Yang Wu, Weiwei Zhong, Ningren Cui, Christopher M. Johnson, Hao Xing, Shuang Zhang and Chun Jiang

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes

Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have b...

Authors: Kerry A. Pettigrew, Emily Frinton, Ron Nudel, May T. M. Chan, Paul Thompson, Marianna E. Hayiou-Thomas, Joel B. Talcott, John Stein, Anthony P. Monaco, Charles Hulme, Margaret J. Snowling, Dianne F. Newbury and Silvia Paracchini

Complexities of X chromosome inactivation status in female human induced pluripotent stem cells—a brief review and scientific update for autism research

Induced pluripotent stem cells (iPSCs) allow researchers to make customized patient-derived cell lines by reprogramming noninvasively retrieved somatic cells. These cell lines have the potential to faithfully ...

Authors: Mary G. Dandulakis, Kesavan Meganathan, Kristen L. Kroll, Azad Bonni and John N. Constantino

Investigating the effects of copy number variants on reading and language performance

Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs).

Authors: Alessandro Gialluisi, Alessia Visconti, Erik G. Willcutt, Shelley D. Smith, Bruce F. Pennington, Mario Falchi, John C. DeFries, Richard K. Olson, Clyde Francks and Simon E. Fisher

Identification of a distinct developmental and behavioral profile in children with Dup15q syndrome

One of the most common genetic variants associated with autism spectrum disorder (ASD) are duplications of chromosome 15q11.2-q13.1 (Dup15q syndrome). To identify distinctive developmental and behavioral featu...

Authors: Charlotte DiStefano, Amanda Gulsrud, Scott Huberty, Connie Kasari, Edwin Cook, Lawrence T. Reiter, Ronald Thibert and Shafali Spurling Jeste

Persistence of self-injurious behaviour in autism spectrum disorder over 3 years: a prospective cohort study of risk markers

There are few studies documenting the persistence of self-injury in individuals with autism spectrum disorder (ASD) and consequently limited data on behavioural and demographic characteristics associated with ...

Authors: Caroline Richards, Jo Moss, Lisa Nelson and Chris Oliver

Methods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation

Magnetic resonance imaging (MRI) has been widely used in studies evaluating the neuropathology of autism spectrum disorder (ASD). Studies are often limited, however, to higher functioning individuals with ASD....

Authors: Christine Wu Nordahl, Melissa Mello, Audrey M. Shen, Mark D. Shen, Laurie A. Vismara, Deana Li, Kayla Harrington, Costin Tanase, Beth Goodlin-Jones, Sally Rogers, Leonard Abbeduto and David G. Amaral

Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus

Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia differentially impact males and females and are highly heritable. The ways in which sex and genetic vulnerability influence the ...

Authors: Duncan Sinclair, Joseph Cesare, Mary McMullen, Greg C Carlson, Chang-Gyu Hahn and Karin E Borgmann-Winter