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Pathophysiology : the Official Journal... Nov 2023Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger's syndrome, and pervasive developmental disorder. ASD is characterized by...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger's syndrome, and pervasive developmental disorder. ASD is characterized by poor interpersonal relationships and strong attachment. The correlations between activated or inactivated gene products, which occur as a result of genetic mutations affecting neurons in ASD patients, and ASD symptoms are now of critical concern. Here, for the first time, we describe the process in which that the respective ASD-associated mutations (Arg676-to-Cys [R676C] and Ser951-to-Cys [S951C]) of semaphorin-5A (Sema5A) localize Sema5A proteins themselves around the plasma membrane in the N1E-115 cell line, a model line that can achieve neuronal morphological differentiation. The expression of each mutated construct resulted in the promotion of excessive elongation of neurite-like processes with increased differentiation protein markers; R676C was more effective than S951C. The differentiated phenotypes were very partially neutralized by an antibody, against Plexin-B3 as the specific Sema5A receptor, suggesting that the effects of Sema5A act in an autocrine manner. R676C greatly increased the activation of c-Jun N-terminal kinase (JNK), one of the signaling molecules underlying process elongation. In contrast, the blocking of JNK signaling, by a chemical JNK inhibitor or an inhibitory construct of the interaction of RhoG with Elmo1 as JNK upstream signaling molecules, recovered the excessive process elongation. These results suggest that ASD-associated mutations of Sema5A, acting through the JNK signaling cascade, lead to excessive differentiated phenotypes, and the inhibition of JNK signaling recovers them, revealing possible therapeutic targets for recovering the potential molecular and cellular phenotypes underlying certain ASD symptoms.
PubMed: 38133141
DOI: 10.3390/pathophysiology30040040 -
Imaging Neuroscience (Cambridge, Mass.) Oct 2023Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons,...
Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons, and a growing body of work has demonstrated the importance of careful quality control (QC) and evaluated the impact of image and image-processing quality. However, the growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. One of the most important aspects of MRI quality is the accuracy of processed outputs, which have been shown to impact estimated neurodevelopmental trajectories. Here, we evaluate whether the quality of surface reconstructions by FreeSurfer (one of the most widely used MRI processing pipelines) interacts with clinical and demographic factors. We present a tool, FSQC, that enables quick and efficient yet thorough assessment of outputs of the FreeSurfer processing pipeline. We validate our method against other existing QC metrics, including the automated FreeSurfer Euler number, two other manual ratings of raw image quality, and two popular automated QC methods. We show strikingly similar spatial patterns in the relationship between each QC measure and cortical thickness; relationships for cortical volume and surface area are largely consistent across metrics, though with some notable differences. We next demonstrate that thresholding by QC score attenuates but does not eliminate the impact of quality on cortical estimates. Finally, we explore different ways of controlling for quality when examining differences between autistic individuals and neurotypical controls in the Autism Brain Imaging Data Exchange (ABIDE) dataset, demonstrating that inadequate control for quality can alter results of case-control comparisons.
PubMed: 38495338
DOI: 10.1162/imag_a_00022 -
Journal of Affective Disorders Apr 2024The high prevalence of stress-related disorders and depression underscores the urgent need to unravel their impact on individual well-being. This study aim to...
Differences in psychiatric comorbidity patterns in patients diagnosed with chronic stress-induced exhaustion disorder and depression - A cohort study in the total population of Region Stockholm.
The high prevalence of stress-related disorders and depression underscores the urgent need to unravel their impact on individual well-being. This study aim to investigate common psychiatric and stress-related diagnoses, along with postviral fatigue, in individuals with prior stress-induced exhaustion disorder (SED) and prior depression compared to those without prior SED or depression, and to study whether the psychiatric comorbidity patterns differ. The study includes individuals in Region Stockholm who, in 2011, did not have a diagnosis of SED or depression. ICD-10 diagnosis of SED, depression, or both, recorded in 2012-2013, were compared to individuals without prior SED or depression in a cohort (n = 1,362,886), aged 18 to 65. Odds ratios (OR) with 99 % confidence intervals, adjusted for age and neighborhood socioeconomic status, were calculated for psychiatric disorders and post-viral fatigue in 2014-2022. Patients with prior SED showed associations primarily with stress related diagnoses, including acute stress reaction, reaction to severe stress, as well as post-COVID-19 and post-viral fatigue syndrome. These ORs were all larger for SED than depression. Depression was primarily associated with post-traumatic stress disorder (PTSD), alcohol related and substance use disorders, schizophrenia, schizotypal disorders, delusional disorders, manic episode, bipolar affective disorder, persistent mood disorder, neurotic disorder, borderline personality disorder, autistic disorder, Asperger's syndrome, attention -deficit hyperactivity disorder, attention-deficit disorders ADHD/ADD), and suicide attempt. These ORs were all higher for depression, although autistic disorders, ADHD/ADD and PTSD were also highly associated with prior SED (OR > 3.5). The divergent psychiatric comorbidity patterns suggest different underlying mechanisms and clinical prognosis.
Topics: Humans; Stress Disorders, Post-Traumatic; Cohort Studies; Depression; Comorbidity; Attention Deficit Disorder with Hyperactivity; Fatigue Syndrome, Chronic; Fatigue
PubMed: 38331048
DOI: 10.1016/j.jad.2024.01.273 -
Healthcare (Basel, Switzerland) Nov 2023Individuals with High-Functioning Autism present impairments in communication, social interaction, and motor development. A low level of motor skills, namely...
Individuals with High-Functioning Autism present impairments in communication, social interaction, and motor development. A low level of motor skills, namely difficulties in gross and fine mobility, and in motor control, discourage individuals with High-Functioning Autism from being involved in physical activities, resulting in fewer opportunities for social interaction. There is not much evidence available about the effects of regular swimming exercise and/or aquatic therapy on health promotion in adults with High-Functioning Autism. An adult male (22 yrs) diagnosed with High-Functioning Autism participated in a combined 6-month swimming and aquatic therapy program (two sessions/week, 60 min each). The pre- and post-intervention assessments consisted of physical fitness, balance, functional ability, and psychomotor tests. The post-intervention assessments showed improvements in the standing long jump (+100%), hand grip force (+71.7%), bend arm hang test (+123.1%), and the physiological parameters in the 6 min walk test (+10.2%). On the opposite, decrements in the sit-up (-12%) and sit-and-reach test (-6.3%) were observed. It was noted that the participant frequently lost interest and focus quickly, resulting in the abandonment of the exercise. Conclusively, there is a great need for further research on this topic examining a larger adult population.
PubMed: 37998478
DOI: 10.3390/healthcare11222986 -
Frontiers in Psychiatry 2023While stigma toward autistic individuals has been well documented, less is known about how autism is perceived relative to other stigmatized disabilities. As a highly...
INTRODUCTION
While stigma toward autistic individuals has been well documented, less is known about how autism is perceived relative to other stigmatized disabilities. As a highly stigmatized condition with similar social cognitive features to autism, schizophrenia may offer a useful comparison for stigma. Previous studies have found that autistic people may be perceived more favorably than those with schizophrenia, but little is known about the underlying volitional thoughts that contribute to differences in how these conditions are perceived.
METHODS
The present study utilizes a mixed-methods approach, allowing for a detailed understanding of how young adults perceive different diagnostic labels. 533 college undergraduates completed questionnaires reflecting their perceptions of one of eight diagnostic labels: four related to autism (autism, autistic, autism spectrum disorder, or Asperger's), two related to schizophrenia (schizophrenia or schizophrenic), and two related to an unspecified clinical condition (clinical diagnosis or clinical disorder). Participants also completed an open-ended question regarding their thoughts about, and exposure to, these labels. Responses were compared across broader diagnostic categories (autism, schizophrenia, general clinical condition), with thematic analysis used to assess the broader themes occurring within the open-ended text.
RESULTS
While perceptions did not differ significantly for person-first and identity-first language within labels, several differences were apparent across labels. Specifically, quantitative results indicated greater prejudice towards autism and schizophrenia than the generic clinical condition, with schizophrenia associated with more perceived fear and danger, as well as an increased preference for social distance, compared to autism. Patterns in initial codes differed across diagnostic labels, with greater variation in responses about autism than responses about schizophrenia or the general clinical condition. While participants described a range of attitudes toward autism (patronizing, exclusionary, and accepting) and schizophrenia (fear, prejudice, and empathy), they refrained from describing their attitudes toward the general clinical label, highlighting the centrality of a cohesive group identity for the development of stigma. Finally, participants reported a number of misconceptions about autism and schizophrenia, with many believing features such as savant syndrome to be core characteristics of the conditions.
CONCLUSION
These findings offer a more detailed account of how non-autistic individuals view autism and may therefore aid in the development of targeted programs to improve attitudes toward autism.
PubMed: 37965364
DOI: 10.3389/fpsyt.2023.1263525 -
ENeurologicalSci Dec 2023The characteristics of functional limb weakness (FLW) as one of the manifestations of functional neurological disorder after vaccination against coronavirus disease 2019...
BACKGROUND
The characteristics of functional limb weakness (FLW) as one of the manifestations of functional neurological disorder after vaccination against coronavirus disease 2019 (COVID-19) remain controversial.
METHODS
In this descriptive case series, we aimed to elucidate the characteristics of Japanese patients with FLW who claimed muscle weakness after COVID-19 vaccination among patients who visited our outpatient clinic between 1 June 2021 and 31 December 2022.
RESULTS
Nine patients were diagnosed with FLW (mean age: 30.8 years), including two men and seven women. Seven patients were vaccinated with the BioNTech/Pfizer vaccine and two with the mRNA-1273 Moderna vaccine. All patients demonstrated various positive signs for FLW. Magnetic resonance imaging or computed tomography indicated no abnormality that could explain their symptoms. At the time of the clinic visit, five patients were treated for psychiatric disorders, including depression, insomnia, attention-deficit hyperactivity disorder, and Asperger's syndrome. Muscle weakness spread to the limbs beyond the vaccinated arm in seven patients.
CONCLUSIONS
We describe the basic characteristics of FLW in Japanese patients after COVID-19 vaccination. Further recognition of these characteristics could aid the diagnosis of FLW by physicians allowing them to support these patients effectively.
PubMed: 38046447
DOI: 10.1016/j.ensci.2023.100487 -
Iranian Journal of Psychiatry Feb 2024Early detection of autism spectrum disorder (ASD) can lead to earlier intervention and greater improvement of children's quality of life and performance; hence, the use...
Early detection of autism spectrum disorder (ASD) can lead to earlier intervention and greater improvement of children's quality of life and performance; hence, the use of screening tools is essential to facilitate the diagnosis process. The aim of the present study was to determine the clinical and differential validity of Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ) in a group of children and adolescents with autism spectrum disorder compared to a normal developmental group. The study was conducted in Roozbeh Hospital involving 52 children with ASD and 53 typically developing (TD) children, aged between 4-12 years. Their parents completed the SRS-2 and SCQ. These children were also interviewed using the Childhood Autism Rating Scale, 2nd Edition (CARS-2) and Asperger Syndrome Diagnostic Scale (ASDS). After completion, the results were analyzed using the SPSS Version 18 software and a significant level of 0.05. The average age of children in the autism group was 7.5 ± 2.7 years, while in the typically developing (TD) children group, it was 7.7 ± 2.3 years (P = 0.656). A positive correlation coefficient was observed between the CARS questionnaire score, the SRS questionnaire score, the SCQ questionnaire score, and the ASDS (P < 0.01). In the SRS questionnaire, the area under the ROC curve was 0.976, and in the SCQ questionnaire it was 0.953, both of which had a good and significant diagnostic value (P < 0.001). A sensitivity of 0.942 and specificity of 0.811 for the cut-off point of 62.5 were obtained in the SRS questionnaire. Additionally, a sensitivity of 0.865 and specificity of 0.925 for the cut-off point of 15.5 were achieved in the SCQ questionnaire. The SRS-2 and the SCQ are sensitive and specific tools for identifying and discriminating children with autism spectrum disorder.
PubMed: 38686312
DOI: 10.18502/ijps.v19i2.15108 -
Current Issues in Molecular Biology Apr 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger's syndrome, and pervasive developmental disorder. Individuals with ASD may...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger's syndrome, and pervasive developmental disorder. Individuals with ASD may exhibit difficulties in social interactions, communication challenges, repetitive behaviors, and restricted interests. While genetic mutations in individuals with ASD can either activate or inactivate the activities of the gene product, impacting neuronal morphogenesis and causing symptoms, the underlying mechanism remains to be fully established. Herein, for the first time, we report that genetically conserved Rac1 guanine-nucleotide exchange factor (GEF) Dock5 signalosome molecules control process elongation in the N1E-115 cell line, a model line capable of achieving neuronal morphological changes. The increased elongation phenotypes observed in ASD and intellectual disability (ID)-associated Semaphorin-5A (Sema5A) Arg676-to-Cys [p.R676C] were also mediated by Dock5 signalosome molecules. Indeed, knockdown of Dock5 using clustered regularly interspaced short palindromic repeat (CRISPR)/CasRx-based guide(g)RNA specifically recovered the mutated Sema5A-induced increase in process elongation in cells. Knockdown of Elmo2, an adaptor molecule of Dock5, also exhibited similar recovery. Comparable results were obtained when transfecting the interaction region of Dock5 with Elmo2. The activation of c-Jun N-terminal kinase (JNK), one of the primary signal transduction molecules underlying process elongation, was ameliorated by either their knockdown or transfection. These results suggest that the Dock5 signalosome comprises abnormal signaling involved in the process elongation induced by ASD- and ID-associated Sema5A. These molecules could be added to the list of potential therapeutic target molecules for abnormal neuronal morphogenesis in ASD at the molecular and cellular levels.
PubMed: 38666924
DOI: 10.3390/cimb46040194 -
Lancet Regional Health. Americas May 2024Patients with autism spectrum disorders (ASD) experience higher rates of perioperative anxiety and are likely to receive premedication. Little is known about...
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). We included all surgical patients aged three to twelve years, with a formal diagnosis of ASD, Asperger's Syndrome, or pervasive developmental disorder not otherwise specified. Preoperative behaviors were recorded by an unblinded nurse utilizing the validated Modified Yale Preoperative Anxiety Scale (mYPAS). The difference in score on the mYPAS was the primary outcome, and an intention-to-treat analysis was employed. A generalized estimating equations model was used to compare mYPAS scores controlling for significant independent variables.
FINDINGS
58 patients were analyzed after 1:1 randomization of 30 patients to each group. Groups were balanced except the median number of intraoperative pain medications was significantly lower in the ASE group (1 vs. 3, p = 0.012). Mean (SD) age for all patients was 7.2 (2.9) years, range 2.6-12.7. 72.4% (42/58) were White and all were Non-Hispanic or Latino. 74% were Male (21/30 ASE and 22/28 Control) and 26% were Female (9/30 ASE and 6/28 Control). No differences were found in mYPAS scores between groups at three time periods (43.5 vs. 42, p = 0.88, 47.8 vs. 48.4, p = 0.76, and 36.4 vs. 43.8, p = 0.15, ASE vs. control group, respectively). The ASE group had a significant within-group decrease in mYPAS scores from nursing intake to transition (p = 0.030).
INTERPRETATION
An ASE did not significantly reduce perioperative anxiety. However, the promising results deserve further investigation.
FUNDING
Dayton Children's Hospital Foundation Robert C. Cohn Memorial Research Grant.
PubMed: 38645550
DOI: 10.1016/j.lana.2024.100736 -
Asian Journal of Surgery Dec 2023
Topics: Humans; Asperger Syndrome; Comorbidity; Depressive Disorder, Major; Syncope; Male; Adolescent
PubMed: 37635025
DOI: 10.1016/j.asjsur.2023.08.085