Specialization of the brain for language in children with Fragile X Syndrome: a functional Near Infrared Spectroscopy study.

Specialization of the brain for language is early emerging and essential for language learning in young children. Fragile X Syndrome (FXS) is a neurogenetic disorder marked by high rates of delays in both expressive and receptive language, but neural activation patterns during speech and language processing are unknown. We report results of a functional Near Infrared Spectroscopy (fNIRS) study of responses to speech and nonspeech sounds in the auditory cortex in a sample of 2- to 10-year-old children with FXS and typically developing controls (FXS n = 23, TDC n = 15, mean age = 6.

Results from a Double-Blind, Randomized, Placebo-Controlled, Single-Dose, Crossover Trial of Lovastatin or Minocycline in Fragile X Syndrome.

Treatment studies in knockout rodent models have found that minocycline and lovastatin each improve synaptic, neurological, and behavioral functioning, and open-label chronic dosing studies in human patients with fragile X syndrome (FXS) have demonstrated modest clinical improvements. Findings from blinded studies are mixed, and there is a limited understanding of electrophysiological target engagement that would facilitate cross-species translational studies. Smaller-scale, acute (e.

Frontal Cortex Hyperactivation and Gamma Desynchrony in Fragile X Syndrome: Correlates of Auditory Hypersensitivity.

Fragile X syndrome (FXS) is an X-linked disorder that often leads to intellectual disability, anxiety, and sensory hypersensitivity. While sound sensitivity (hyperacusis) is a distressing symptom in FXS, its neural basis is not well understood. It is postulated that hyperacusis may stem from temporal lobe hyperexcitability or dysregulation in top-down modulation.

Reliability of resting-state electrophysiology in fragile X syndrome.

Objective: Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models.

Safety and Efficacy of Paliperidone Palmitate in Pediatric Patients with Autism and Intellectual Disability.

This retrospective chart review examines the safety, tolerability and effectiveness of long acting injectable paliperidone palmitate (P-LAI) targeting irritability in twenty-six youth and transition-aged individuals with autism spectrum disorder (ASD) and/or intellectual disability (ID) over a 3-year window. Clinical response was evaluated via prospectively assigned Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) scales as well as number of hospital presentations. P-LAI was well tolerated with only 3 patients stopping P-LAI due to side effects.

Neurodevelopmental Disorders Including Autism Spectrum Disorder and Intellectual Disability as a Risk Factor for Delayed Diagnosis of Catatonia.

Objective: Catatonia is a distinct and severe medical syndrome comprising motor, somatic, and psychiatric symptoms that is reported in upwards of 17% of young patients with autism spectrum disorders. Clinical experience indicates catatonia is often under-recognized in this clinical population. Here we characterize the clinical presentation of catatonia in patients with and without neurodevelopmental disorders (NDDs) including autism, including the time from symptom onset to diagnosis of catatonia.

Genetic syndromes are prevalent in patients with comorbid neurodevelopmental disorders and catatonia.

Catatonia occurs at high rates in idiopathic and syndromic neurodevelopmental disorders. At our institution's multidisciplinary catatonia clinic, clinical genetic testing (including microarray, fragile X PCR and methylation, autism/ID expanded panels, and exome sequencing) was commonly completed as part of clinical workup on patients with co-occurring neurodevelopmental disorders and catatonia (performed in 36/48 cases or 75%). This testing identified a pathogenic or likely pathogenic finding in 15/36 patients (42%).

A sensitive and reproducible qRT-PCR assay detects physiological relevant trace levels of FMR1 mRNA in individuals with Fragile X syndrome.

Fragile X syndrome (FXS) is the most common inherited intellectual disability. FXS is caused by a trinucleotide repeat expansion in the 5' untranslated region of the FMR1 gene, which leads to gene methylation, transcriptional silencing, and lack of expression of Fragile X Messenger Riboprotein (FMRP). Currently available FXS therapies are inefficient, and the disease severity is highly variable, making it difficult to predict disease trajectory and treatment response.

Lymphocytic Extracellular Signal-Regulated Kinase Dysregulation in Autism Spectrum Disorder.

Objective: Extracellular signal-regulated kinase (ERK1/2) is a conserved central intracellular signaling cascade involved in many aspects of neuronal development and plasticity. Converging evidence support investigation of ERK1/2 activity in autism spectrum disorder (ASD). We previously reported enhanced baseline lymphocytic ERK1/2 activation in autism, and now we extend our work to investigate the early phase kinetics of lymphocytic ERK1/2 activation in idiopathic ASD.

Systematic Review: Emotion Dysregulation in Syndromic Causes of Intellectual and Developmental Disabilities.

Objective: To summarize the current state of the literature regarding emotion dysregulation (ED) in syndromic intellectual disabilities (S-IDs) in 6 of the most common forms of S-IDs-Down syndrome, fragile X syndrome (FXS), tuberous sclerosis complex, Williams syndrome, Prader-Willi syndrome, and Angelman syndrome-and to determine future research directions for identification and treatment of ED.

Method: PubMed bibliographic database was searched from date of inception to May 2021. PRISMA 2020 guidelines were followed with the flowchart, table of included studies, list of excluded studies, and checklist provided.

Brief Report: Telehealth Satisfaction Among Caregivers of Pediatric and Adult Psychology and Psychiatry Patients with Intellectual and Developmental Disability in the Wake of Covid-19.

Telehealth has been shown to be both acceptable and effective in many areas of healthcare, yet it was not widely adopted prior to the SARS-CoV-2 (COVID-19) pandemic. Additionally, previous evaluations of telehealth for autism spectrum condition (ASC) and intellectual and developmental disability (IDD) populations are limited in both number and scope. Here, we investigated satisfaction amongst Psychology and Psychiatry patient caregivers at Cincinnati Children's Hospital Medical Center (CCHMC) after the onset of the COVID-19 pandemic.

A Collaborative Psychiatric-Genetics Inpatient Care Delivery Model Improves Access to Clinical Genetic Evaluation, Testing, and Diagnosis for Patients With Neurodevelopmental Disorders.

Neurodevelopmental disorders including autism spectrum disorder, intellectual disability, and global developmental delay are among the most common indications for referral to clinical genetics evaluation; and clinical genetic testing is indicated for people with neurodevelopmental disorders. There are known barriers to care in accessing clinical genetics evaluation for this patient population. We created a collaborative psychiatric-genetics consultation service and psychiatric-genetics outpatient clinic with the goal to improve care delivery to patients with neurodevelopmental disorders.

Children with ASD establish joint attention during free-flowing toy play without face looks.

Children's ability to share attention with another person (i.e., achieve joint attention) is critical for learning about their environments in general and supporting language and object word learning in particular.

Neocortical localization and thalamocortical modulation of neuronal hyperexcitability contribute to Fragile X Syndrome.

Fragile X Syndrome (FXS) is a monogenetic form of intellectual disability and autism in which well-established knockout (KO) animal models point to neuronal hyperexcitability and abnormal gamma-frequency physiology as a basis for key disorder features. Translating these findings into patients may identify tractable treatment targets. Using source modeling of resting-state electroencephalography data, we report findings in FXS, including 1) increases in localized gamma activity, 2) pervasive changes of theta/alpha activity, indicative of disrupted thalamocortical modulation coupled with elevated gamma power, 3) stepwise moderation of low and high-frequency abnormalities based on female sex, and 4) relationship of this physiology to intellectual disability and neuropsychiatric symptoms.

Optimization, validation and initial clinical implications of a Luminex-based immunoassay for the quantification of Fragile X Protein from dried blood spots.

Fragile X Syndrome (FXS) is caused by a trinucleotide expansion leading to silencing of the FMR1 gene and lack of expression of Fragile X Protein (FXP, formerly known as Fragile X Mental Retardation Protein, FMRP). Phenotypic presentation of FXS is highly variable, and the lack of reproducible, sensitive assays to detect FXP makes evaluation of peripheral FXP as a source of clinical variability challenging. We optimized a Luminex-based assay to detect FXP in dried blot spots for increased reproducibility and sensitivity by improving reagent concentrations and buffer conditions.

Evidence for Three Subgroups of Female Premutation Carriers Defined by Distinct Neuropsychiatric Features: A Pilot Study.

Over 200 Cytosine-guanine-guanine (CGG) trinucleotide repeats in the 5' untranslated region of the Fragile X mental retardation 1 () gene results in a "full mutation," clinically Fragile X Syndrome (FXS), whereas 55 - 200 repeats result in a "premutation." premutation carriers (PMC) are at an increased risk for a range of psychiatric, neurocognitive, and physical conditions. Few studies have examined the variable expression of neuropsychiatric features in female PMCs, and whether heterogeneous presentation among female PMCs may reflect differential presentation of features in unique subgroups.

Psychotropic Drug Treatment Patterns in Persons with Fragile X Syndrome.

Psychiatric comorbidity is common in fragile X syndrome (FXS) and often addressed through pharmacological management. Here we examine data in the Fragile X Online Registry With Accessible Research Database (FORWARD) to characterize specific symptoms being treated with psychotropic medication, patterns of medication use, as well as the influence of gender, intellectual disability (ID), age, and autism spectrum disorder (ASD) diagnosis. Data were drawn from the 975 participants who have a completed clinician form.

Gaboxadol in Fragile X Syndrome: A 12-Week Randomized, Double-Blind, Parallel-Group, Phase 2a Study.

Fragile X syndrome (FXS), the most common single-gene cause of intellectual disability and autism spectrum disorder (ASD), is caused by a >200-trinucleotide repeat expansion in the 5' untranslated region of the fragile X mental retardation 1 () gene. Individuals with FXS can present with a range of neurobehavioral impairments including, but not limited to: cognitive, language, and adaptive deficits; ASD; anxiety; social withdrawal and avoidance; and aggression. Decreased expression of the γ-aminobutyric acid type A (GABA) receptor subunit and deficient GABAergic tonic inhibition could be associated with symptoms of FXS.

Decades of Progress in the Psychopharmacology of Autism Spectrum Disorder.

Recent decades have been marked by a wave drug treatment research in autism spectrum disorder (ASD). This work has resulted in improved ability to treat commonly occurring behavioral challenges associated with ASD including most prominently irritability marked by aggression, self-injurious behavior, and severe tantrums. While treatment of interfering behavior has progressed in our field, there remain several areas of unmet medical need including most prominently a lack of any approved drug therapies for the core, defining symptoms of autism.

Sex differences in resting EEG power in Fragile X Syndrome.

Electrophysiological alterations may represent a neural substrate of impaired neurocognitive processes and other phenotypic features in Fragile X Syndrome (FXS). However, the role of biological sex in electroencephalography (EEG) patterns that differentiate FXS from typical development has not been determined. This limits use of EEG in both the search for biomarkers of impairment in FXS as well as application of those markers to enhance our understanding of underlying neural mechanisms to speed treatment discovery.

Using head-mounted eye tracking to examine visual and manual exploration during naturalistic toy play in children with and without autism spectrum disorder.

Multimodal exploration of objects during toy play is important for a child's development and is suggested to be abnormal in children with autism spectrum disorder (ASD) due to either atypical attention or atypical action. However, little is known about how children with ASD coordinate their visual attention and manual actions during toy play. The current study aims to understand if and in what ways children with ASD generate exploratory behaviors to toys in natural, unconstrained contexts by utilizing head-mounted eye tracking to quantify moment-by-moment attention.

Recent Advances in the Pharmacological Management of Behavioral Disturbances Associated with Autism Spectrum Disorder in Children and Adolescents.

Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric condition affecting an estimated one in 36 children. Youth with ASD may have severe behavioral disturbances including irritability, aggression, and hyperactivity. Currently, there are only two medications (risperidone and aripiprazole) approved by the US Food and Drug Administration (FDA) for the treatment of irritability associated with ASD.

Brief Report: Intranasal Ketamine in Adolescents and Young Adults with Autism Spectrum Disorder-Initial Results of a Randomized, Controlled, Crossover, Pilot Study.

Dysregulation of glutamate neurotransmission plays a critical role in autism spectrum disorder (ASD) pathophysiology and is a primary target for core deficit research treatment trials. The mechanism of action of ketamine has striking overlap with the theory of ASD as a disorder of synaptic communication and neuronal networks. This two-dose, double-blind, placebo controlled, cross-over pilot trial of intranasal (IN) ketamine targeting core social impairment included individuals with ASD (N = 21) between 14 and 29 years.