Electroconvulsive therapy in autism spectrum disorders: an update to the literature.

Purpose Of Review: Over the last quarter century, the clinical evidence surrounding the use of electroconvulsive therapy (ECT) in individuals with autism spectrum disorder (ASD) has expanded. This review provides the most up-to-date findings on the usage of ECT in ASD and discusses these results within the historical context and direct patient care experience.

Recent Findings: ECT is typically implemented for psychotropic-refractory catatonic, affective, psychotic, and combined pathology for individuals across the lifespan.

The Population-Based Incidence and Prevalence of Catatonia.

Objective: Catatonia is a neuropsychiatric disorder that is associated with a range of medical and psychiatric illnesses. Although many single-center studies have been conducted, uncertainty over the population-based incidence and prevalence of the disorder remains. This study reports on the incidence and prevalence rates of catatonia extrapolated from two large epidemiologic studies in the United Kingdom and United States.

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Discovery of 4-(5-Membered)Heteroarylether-6-methylpicolinamide Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5.

This Letter details our efforts to develop novel, non-acetylene-containing metabotropic glutamate receptor subtype 5 (mGlu) negative allosteric modulators (NAMs) with improved pharmacological properties. This endeavor involved replacing the ether-linked pyrimidine moiety, a metabolic liability, with various 5-membered heterocycles. From this exercise, we identified , a highly brain penetrant and selective mGlu NAM which displayed moderate potency against both human and rat mGlu.

Considerations for Measuring Caregiver Talk in Interactions With Infants at Elevated and Population-Level Likelihood for Autism: Deriving Stable Estimates.

Purpose: This study aims to help researchers design observational measurement systems that yield sufficiently stable scores for estimating caregiver talk among caregivers of infant siblings of autistic and non-autistic children. Stable estimates minimize error introduced by facets of the measurement system, such as variability between coders or measurement sessions.

Method: Analyses of variance were used to partition error variance between coder and session and to derive coefficients.

Discovery of VU0467319: an M Positive Allosteric Modulator Candidate That Advanced into Clinical Trials.

Herein we detail the of VU0467319 (VU319), an M Positive Allosteric Modulator (PAM) clinical candidate that successfully completed a Phase I Single Ascending Dose (SAD) clinical trial. VU319 () is a moderately potent M PAM (M PAM EC = 492 nM ± 2.9 nM, 71.

Links Between Early Prelinguistic Communication and Later Expressive Language in Toddlers With Autistic and Non-Autistic Siblings.

Purpose: The present study explored the extent to which early prelinguistic communication skills predict expressive language in toddlers with autistic siblings (Sibs-autism), who are known to be at high likelihood for autism and language disorder, and a comparison group of toddlers with non-autistic older siblings (Sibs-NA).

Method: Participants were 51 toddlers (29 Sibs-autism, 22 Sibs-NA) aged 12-18 months at the first time point in the study (Time 1). Toddlers were seen again 9 months later (Time 2).

The cannabinoid CB receptor positive allosteric modulator EC21a exhibits complicated pharmacology .

Schizophrenia is a complex disease involving the dysregulation of numerous brain circuits and patients exhibit positive symptoms (hallucinations, delusions), negative symptoms (anhedonia), and cognitive impairments. We have shown that the antipsychotic efficacy of positive allosteric modulators (PAMs) of both the M muscarinic receptor and metabotropic glutamate receptor 1 (mGlu) involve the retrograde activation of the presynaptic cannabinoid type-2 (CB) receptor, indicating that CB activation or potentiation could result in a novel therapeutic strategy for schizophrenia. We used two complementary assays, receptor-mediated phosphoinositide hydrolysis and GIRK channel activation, to characterize a CB PAM scaffold, represented by the compound EC21a, to explore its potential as a starting point to optimize therapeutics for schizophrenia.

Rett syndrome.

Rett syndrome (RTT) is a severe, progressive, neurodevelopmental disorder, which affects predominantly females. In most cases, RTT is associated with pathogenic variants in MECP2. MeCP2, the protein product of MECP2, is known to regulate gene expression and is highly expressed in the brain.

A Case of Catatonia in a 37-Month-Old Child With MOG-Antibody-Positive Acute Disseminated Encephalomyelitis.

In this Letter to the Editor, we examine a case of catatonia in a 37-month-old child with myelin oligodendrocyte glycoprotein (MOG) antibody-positive acute disseminated encephalomyelitis (ADEM). To our knowledge, this is one of the youngest cases of non-drug-related catatonia reported in the literature. We will discuss how this patient's symptoms of catatonia responded to pharmacologic interventions and the need to screen young children for catatonic symptoms, given the high rate of morbidity and mortality associated with the condition.

The missing clinical guidance: a scoping review of care for autistic transgender and gender-diverse people.

Unlabelled: The co-occurrence of autism and gender diversity has been increasingly studied in the past decade. It is estimated that ∼11% of transgender and gender-diverse (TGD) individuals are diagnosed with autism. However, there is insufficient knowledge about appropriate gender-related clinical care for autistic TGD individuals.

Elucidating the molecular logic of a metabotropic glutamate receptor heterodimer.

Metabotropic glutamate (mGlu) receptor protomers can heterodimerize, leading to different pharmacology compared to their homodimeric counterparts. Here, we use complemented donor-acceptor resonance energy transfer (CODA-RET) technology that distinguishes signaling from defined mGlu heterodimers or homodimers, together with targeted mutagenesis of receptor protomers and computational docking, to elucidate the mechanism of activation and differential pharmacology in mGlu heteromers. We demonstrate that positive allosteric modulators (PAMs) that bind an upper allosteric pocket in the mGlu transmembrane domain are active at both mGlu homomers and mGlu heteromers, while those that bind a lower allosteric pocket within the same domain are efficacious in homomers but not heteromers.

Discovery of VU6016235: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM).

Herein, we report structure-activity relationship (SAR) studies to develop novel tricyclic M PAM scaffolds with improved pharmacological properties. This endeavor involved a "tie-back" strategy to replace a 5-amino-2,4-dimethylthieno[2,3-]pyrimidine-6-carboxamide core, which led to the discovery of two novel tricyclic cores. While both tricyclic cores displayed low nanomolar potency against both human and rat M and were highly brain-penetrant, the 2,4-dimethylpyrido[4',3':4,5]thieno[2,3-]pyrimidine tricycle core provided lead compound, , with an overall superior pharmacological and drug metabolism and pharmacokinetics (DMPK) profile, as well as efficacy in a preclinical antipsychotic animal model.

Remote Microphone Systems for Autistic and Nonautistic Youth: Effects on Audiovisual Task Engagement.

Objectives: A recent study has provided empirical support for the use of remote microphone (RM) systems to improve listening-in-noise performance of autistic youth. It has been proposed that RM system effects might be achieved by boosting engagement in this population. The present study used behavioral coding to test this hypothesis in autistic and nonautistic youth listening in an ecologically valid, noisy environment.

Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism with and without Profound Impairment: An Observational Study.

Introduction: Catatonia is a highly morbid psychomotor and affective disorder which can affect autistic individuals with and without profound impairment. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments has not been described.

Methods: We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1, 2021 to May 31, 2024.

Modeling antisense oligonucleotide therapy in MECP2 duplication syndrome human iPSC-derived neurons reveals gene expression programs responsive to MeCP2 levels.

Genomic copy-number variations (CNVs) that can cause neurodevelopmental disorders often encompass many genes, which complicates our understanding of how individual genes within a CNV contribute to pathology. MECP2 duplication syndrome (MDS or MRXSL in OMIM; OMIM#300260) is one such CNV disorder caused by duplications spanning methyl CpG-binding protein 2 (MECP2) and other genes on Xq28. Using an antisense oligonucleotide (ASO) to normalize MECP2 dosage is sufficient to rescue abnormal neurological phenotypes in mouse models overexpressing MECP2 alone, implicating the importance of increased MECP2 dosage within CNVs of Xq28.

Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals.

The Development of a Pediatric Catatonia Clinical Roadmap for Clinical Care at Vanderbilt University Medical Center.

Background: Pediatric catatonia is associated with a high degree of morbidity and mortality in children. However, pediatric catatonia is highly responsive to treatment if rapidly identified and appropriate interventions are administered. To our knowledge, there are no current publications which propose a systematic approach for the management of pediatric catatonia.