Spectrum Disorder

Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD...

Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1-2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups. The phenotype and genomic data of patients with DD/ID were further retrospectively analyzed...

Human brain organization involves the coordinated expression of thousands of genes. For example, the first principal component (C1) of cortical transcription identifies a hierarchy from sensorimotor to association regions. In this study, optimized processing of the Allen Human Brain Atlas revealed two new components of cortical gene expression architecture, C2 and C3, which are distinctively enriched for neuronal, metabolic and immune processes, specific cell types and cytoarchitectonics, and genetic variants associated with intelligence...

Synaptic dysfunction is a key feature of SHANK-associated disorders such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we aimed to investigate such alterations in ex11|SH3 SHANK3-KO mice combining expansion and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins in both human and murine brain tissue. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molecular organization of subsynaptic domains under SHANK3-deficient conditions...

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan...

The global prevalence of overweight and obesity is a significant public health concern that also largely affects women of childbearing age. Human epidemiological studies indicate that prenatal exposure to excessive maternal weight or excessive gestational weight gain is linked to various neurodevelopmental disorders in children, including attention deficit hyperactivity disorder, autism spectrum disorder, internalizing and externalizing problems, schizophrenia, and cognitive/intellectual impairment. Considering that inadequate maternal body mass can induce serious disorders in offspring, it is important to increase efforts to prevent such outcomes...

Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network - an early-emerging neural network involved in orienting attention to the most salient aspects of one's internal and external environment - may predict the development of ASD symptoms such as reduced social attention and atypical sensory processing...

Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities...

Gaucher disease (GD) is an autosomal recessively inherited lysosomal storage disorder caused by biallelic pathological variants in the GBA1 gene. Patients present along a broad clinical spectrum, and phenotypes are often difficult to predict based on genotype alone. The variant R463C (p.Arg502Cys) exemplifies this challenge. To better characterize its different clinical presentations, we examined the records of 25 current and historical patients evaluated at the National Institutes of Health. Nine patients were classified as GD1, 14 were classified as GD3, and two had an ambiguous diagnosis between GD1 and GD3...

UNLABELLED: Numerous studies have supported that nonalcoholic fatty liver disease (NAFLD) is highly associated with gut microbiota dysbiosis. Ling-Gui-Zhu-Gan decoction (LG) has been clinically used to treat NAFLD, but the underlying mechanism remains unknown. This study investigated the therapeutic effect and mechanisms of LG in mice with NAFLD induced by a high-fat diet (HD). An HD-induced NAFLD mice model was established to evaluate the efficacy of LG followed by biochemical and histopathological analysis...

NKAP mutations are associated with Hackmann-Di Donato-type X-linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation-associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP transcription within HEK293T cells transfected with NKAP p...

BACKGROUND: Optic neuritis (ON) is a common feature of inflammatory demyelinating diseases (IDDs) such as multiple sclerosis (MS), aquaporin 4-antibody neuromyelitis optica spectrum disorder (AQP4 + NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the involvement of the optic chiasm (OC) in IDD has not been fully investigated. AIMS: To examine OC differences in non-acute IDD patients with (ON+) and without ON (ON-) using magnetisation transfer ratio (MTR), to compare differences between MS, AQP4 + NMOSD and MOGAD and understand their associations with other neuro-ophthalmological markers...

INTRODUCTION: Acute kidney injury (AKI) frequently develops in patients receiving cancer therapy and requires a wide differential diagnosis due to possible role of unique cancer and drug-related factors, in addition to common pre- and post-renal causes. Rapid development of new molecular targeted anti-cancer drugs and immunotherapies has opened unprecedented possibilities of treatment at the price of an increased spectrum of renal side effects. AREAS COVERED: The present review aims at providing a state-of-the-art picture of AKI in cancer patient (PubMed and Embase libraries were searched from inception to January 2024), with a focus on differential diagnosis and management of diverse clinical settings...

Neurodegenerative diseases (amyloid diseases such as Alzheimer's and Parkinson's), stemming from protein misfolding and aggregation, encompass a spectrum of disorders with severe systemic implications. Timely detection is pivotal in managing these diseases owing to their significant impact on organ function and high mortality rates. The diverse array of amyloid disorders, spanning localized and systemic manifestations, underscores the complexity of these conditions and highlights the need for advanced detection methods...

Circular dichroism (CD) spectroscopy is an analytical technique that measures the wavelength-dependent differential absorbance of circularly polarized light and is applicable to most biologically important macromolecules, such as proteins, nucleic acids, and carbohydrates. It serves to characterize the secondary structure composition of proteins, including intrinsically disordered proteins, by analyzing their recorded spectra. Several computational tools have been developed to interpret protein CD spectra. These methods have been calibrated and tested mostly on globular proteins with well-defined structures, mainly due to the lack of reliable reference structures for disordered proteins...

BACKGROUND AND OBJECTIVES: Neurocognitive deficits in bipolar disorder (BD) have a negative impact on the quality of life, even during the euthymic phase. And many studies conducted to improve cognitive deficits in bipolar disorder. This systematic review aims to summarize studies on cognitive rehabilitation (CR) conducted in bipolar patients and evaluate its impact on neurocognitive deficits. The primary objective is to explore how CR interventions can enhance cognitive functioning, treatment outcomes, and overall quality of life in this population...

Gastroesophageal reflux disease (GERD), a prevalent condition with multifactorial pathogenesis, involves esophageal motor dysmotility as a key contributing factor to its development. When suspected GERD patients have an inadequate response to proton-pump inhibitor (PPI) therapy and normal upper endoscopy results, high-resolution manometry (HRM) is utilized to rule out alternative diagnosis such as achalasia spectrum disorders, rumination, or supragastric belching. At present, HRM continues to provide supportive evidence for diagnosing GERD and determining the appropriate treatment...

PURPOSE: Nicotine withdrawal is a multifaceted physiological and psychological process that can induce a spectrum of mood disturbances. Gaining a more nuanced understanding of how pure nicotine withdrawal influences cognitive control functions may provide valuable insights for the enhancement of smoking cessation programs. This study investigated changes in inhibitory control function in smokers after 2-hour nicotine withdrawal using the event-related potential (ERP) technique. PARTICIPANTS AND METHODS: 28 nicotine dependence (ND) patients and 28 health controls (HCs) completed a smoking-cued Go/No-go task containing two different types of picture stimuli, smoking-cued and neutral picture stimuli...

BACKGROUND: Patients with autism spectrum disorders (ASD) experience higher rates of perioperative anxiety and are likely to receive premedication. Little is known about nonpharmaceutical interventions which may decrease anxiety. This study aims to evaluate the use of an adaptive sensory environment (ASE) to reduce ASD patient anxiety during the perioperative process. METHODS: Our feasibility study (ClinicalTrials.govNCT04994613) enrolled 60 patients in two parallel groups randomized to a control (no ASE) or intervention group (ASE)...

Motor dysfunction is increasingly being viewed as a core characteristic of autism spectrum disorder (ASD) in children. In particular, children with ASD have difficulty in learning new motor skills and there is a need to develop effective methods to improve this. Previous research has found that children with ASD may retain the ability to implicitly learn motor skills in comparison to their explicit learning of motor skills, which is typically impaired. This literature mini review focuses on summarizing the study of implicit learning in the acquisition of motor skills in children with ASD...