scholarly journals Role of Oligodendrocytes and Myelin in the Pathophysiology of Autism Spectrum Disorder

2020 ◽  
Vol 10 (12) ◽  
pp. 951
Author(s):  
Alma Y. Galvez-Contreras ◽  
David Zarate-Lopez ◽  
Ana L. Torres-Chavez ◽  
Oscar Gonzalez-Perez

Autism Spectrum Disorder (ASD) is an early neurodevelopmental disorder that involves deficits in interpersonal communication, social interaction, and repetitive behaviors. Although ASD pathophysiology is still uncertain, alterations in the abnormal development of the frontal lobe, limbic areas, and putamen generate an imbalance between inhibition and excitation of neuronal activity. Interestingly, recent findings suggest that a disruption in neuronal connectivity is associated with neural alterations in white matter production and myelination in diverse brain regions of patients with ASD. This review is aimed to summarize the most recent evidence that supports the notion that abnormalities in the oligodendrocyte generation and axonal myelination in specific brain regions are involved in the pathophysiology of ASD. Fundamental molecular mediators of these pathological processes are also examined. Determining the role of alterations in oligodendrogenesis and myelination is a fundamental step to understand the pathophysiology of ASD and identify possible therapeutic targets.

2020 ◽  
Vol 14 ◽  
Author(s):  
Federica Filice ◽  
Lucia Janickova ◽  
Thomas Henzi ◽  
Alessandro Bilella ◽  
Beat Schwaller

The prevalence of autism spectrum disorder (ASD)—a type of neurodevelopmental disorder—is increasing and is around 2% in North America, Asia, and Europe. Besides the known genetic link, environmental, epigenetic, and metabolic factors have been implicated in ASD etiology. Although highly heterogeneous at the behavioral level, ASD comprises a set of core symptoms including impaired communication and social interaction skills as well as stereotyped and repetitive behaviors. This has led to the suggestion that a large part of the ASD phenotype is caused by changes in a few and common set of signaling pathways, the identification of which is a fundamental aim of autism research. Using advanced bioinformatics tools and the abundantly available genetic data, it is possible to classify the large number of ASD-associated genes according to cellular function and pathways. Cellular processes known to be impaired in ASD include gene regulation, synaptic transmission affecting the excitation/inhibition balance, neuronal Ca2+ signaling, development of short-/long-range connectivity (circuits and networks), and mitochondrial function. Such alterations often occur during early postnatal neurodevelopment. Among the neurons most affected in ASD as well as in schizophrenia are those expressing the Ca2+-binding protein parvalbumin (PV). These mainly inhibitory interneurons present in many different brain regions in humans and rodents are characterized by rapid, non-adaptive firing and have a high energy requirement. PV expression is often reduced at both messenger RNA (mRNA) and protein levels in human ASD brain samples and mouse ASD (and schizophrenia) models. Although the human PVALB gene is not a high-ranking susceptibility/risk gene for either disorder and is currently only listed in the SFARI Gene Archive, we propose and present supporting evidence for the Parvalbumin Hypothesis, which posits that decreased PV level is causally related to the etiology of ASD (and possibly schizophrenia).


Foods ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 49
Author(s):  
Hae Jin Park ◽  
Su Jin Choi ◽  
Yuri Kim ◽  
Mi Sook Cho ◽  
Yu-Ri Kim ◽  
...  

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a lack of social communication and restrictive, repetitive behaviors or interests. This study aimed to examine the mealtime behaviors and food preferences of students with ASD. An online questionnaire on mealtime behavior and food preferences of ASD students was conducted by caregivers including parents, and the average age of ASD students was 14.1 ± 6.1. The analysis of mealtime behavior resulted in classification into three clusters: cluster 1, the “low-level problematic mealtime behavior group”; cluster 2, the “mid-level problematic mealtime behavior group”; and cluster 3, the “high-level problematic mealtime behavior group”. Cluster 1 included older students than other clusters and their own specific dietary rituals. Meanwhile, cluster 3 included younger students than other clusters, high-level problematic mealtime behavior, and a low preference for food. In particular, there were significant differences in age and food preference for each subdivided ASD group according to their eating behaviors. Therefore, the content and method of nutrition education for ASD students’ needs a detailed approach according to the characteristics of each group.


Author(s):  
Wei-Ju Chen ◽  
Zihan Zhang ◽  
Haocen Wang ◽  
Tung-Sung Tseng ◽  
Ping Ma ◽  
...  

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted or repetitive behaviors. Parental perceptions of the etiology of their child’s ASD can affect provider–client relationships, bonding between parents and their children, and the prognosis, treatment, and management of children with ASD. Thus, this study sought to examine the perceptions of ASD etiology of parents of children with ASD. Methods: Forty-two parents of children diagnosed with ASD were recruited across Texas. Semi-structured interviews were conducted individually. All interviews were recorded and later transcribed verbatim for content analysis utilizing NVivo 12.0 (QSR International, Doncaster, Australia). Results: The content analysis identified the following themes regarding parental perceptions of ASD etiology: Genetic factors (40.5%), environmental factors (31.0%), problems that occurred during pregnancy or delivery (23.8%), vaccinations (16.7%), other health problems (7.1%), parental age at the time of pregnancy (4.8%), and spiritual or religious factors (2.4%). Conclusions: The parental perceptions of ASD etiology were diverse, but several views, such as vaccinations and spiritual or religious factors, were not based on scientific evidence. Health professionals and researchers can use these findings to develop and provide targeted education to parents who have children with ASD. Our findings also support policymakers in developing campaigns designed to increase parental ASD awareness and knowledge.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Meng-na Lv ◽  
Hong Zhang ◽  
Yi Shu ◽  
Shan Chen ◽  
Yuan-yuan Hu ◽  
...  

AbstractBackground" Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that impairs a child’s ability to communicate with others. It also includes restricted repetitive behaviors, interests and activities. Symptoms manifest before the age of 3. In the previous studies, we found structural abnormalities of the temporal lobe cortex. High spine densities were most commonly found in ASD subjects with lower levels of cognitive functioning. In the present study, we retrospectively analyzed medical records in relation to the neonatal levels of total serum bilirubin (TSB), neuron-specific enolase (NSE), creatine kinase brain band isoenzyme (CK-BB), and neonatal behavior in ASD patients from Southern China. Methods: A total of 80 patients with ASD (ASD group) were screened for this retrospective study. Among them, 34 were low-functioning ASD (L-ASD group) and 46 were high-functioning ASD (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. For comparison with ASD cases, 80 normal neonates (control group) were selected from the same period. Biochemical parameters, including TSB, NSE and CK-BB in the neonatal period and medical records on neonatal behavior were collected. Results: The levels of serum TSB, NSE and CK-BB in the ASD group were significantly higher when compared with those from the control group (P < 0.01, or P < 0.05). The amounts of serum TSB, NSE and CK-BB in the L-ASD group were significantly higher when compared with those in the H-ASD group (P < 0.01, or P < 0.05). The Neonatal Behavioral Assessment Scale (NBAS) scores in the ASD group were significantly lower than that in the control group (P < 0.05). Likewise, the NBAS scores in the L-ASD group were significantly lower than that in the H-ASD group (P < 0.05). There was no association between serum TSB, NSE, CK-BB and NBAS scores (P > 0.05) in the ASD group. Conclusions: The neonatal levels of TSB, NSE and CK-BB in ASD from Southern China were significantly higher than those of healthy controls. These findings need to be investigated thoroughly by future studies with large sample.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Serap Bilge ◽  
Barış Ekici

Abstract Introduction Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, social interaction, restricted interest, and repetitive behaviors. Although more cases are being diagnosed, no drugs are approved to treat the core symptoms or cognitive and behavioral problems associated with autism. Therefore, there is an urgent need to develop an effective and safe treatment. Objective In this study, we aim to share our 2-year experience with CBD-enriched cannabis treatment in autism and review the latest studies. Materials and methods The study included 33 (27 males, six females) children diagnosed with autism spectrum disorder who were followed up between January 2018 and August 2020. The mean age was 7.7 ± 5.5 years. The average daily dosage of cannabidiol (CBD) was 0.7 mg/kg/day (0.3–2 mg/kg/day). The median duration of treatment was 6.5 months (3–28 months). The preparations used in this study contained full-spectrum CBD and trace elements tetrahydrocannabinol (THC) of less than 3%. Results The outcomes were evaluated before and after treatment based on clinical interviews. At each follow-up visit, parents were asked to evaluate the effectiveness of the CBD-enriched cannabis treatment. According to the parents’ reports, no change in daily life activity was reported in 6 (19.35%) patients. The main improvements of the treatment were as follows: a decrease in behavioral problems was reported in 10 patients (32.2%), an increase in expressive language was reported in 7 patients (22.5%), improved cognition was reported in 4 patients (12,9%), an increase in social interaction was reported in 3 patients (9.6%), and a decrease in stereotypes was reported in 1 patient (3.2%). The parents reported improvement in cognition among patients who adhered to CBD-enriched cannabis treatment for over two years. The antipsychotic drug could be stopped only in one patient who showed mild ASD symptoms. No change could be made in other drug use and doses. Additionally, this study includes an extensive review of the literature regarding CBD treatment in autism spectrum disorder. According to recent studies, the average dose of CBD was 3.8±2.6 mg/kg/day. The ratio of CBD to THC in the used preparations was 20:1. The most significant improvements were seen in the behavioral problems reported in 20–70% of the patients. Conclusion Using lower doses of CBD and trace THC seems to be promising in managing behavioral problems associated with autism. In addition, this treatment could be effective in managing the core symptoms and cognitive functions. No significant side effects were seen at the low doses of CBD-enriched cannabis when compared to other studies.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Masatoshi Nakata ◽  
Ryo Kimura ◽  
Yasuko Funabiki ◽  
Tomonari Awaya ◽  
Toshiya Murai ◽  
...  

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Owing to the difficulty of clinical diagnosis, ASD without intellectual disability (i.e., high-functioning ASD) is often overlooked. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. We identified miR-6126 as being robustly down-regulated in ASD and correlated with the severity of social deficits. Enrichment analysis of predicted target genes revealed potential association with neurons, synapses, and oxytocin signaling pathways. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.


2019 ◽  
Vol 8 (10) ◽  
pp. 1588
Author(s):  
Yunho Jin ◽  
Jeonghyun Choi ◽  
Seunghoon Lee ◽  
Jong Won Kim ◽  
Yonggeun Hong

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is accompanied by social deficits, repetitive and restricted interests, and altered brain development. The majority of ASD patients suffer not only from ASD itself but also from its neuropsychiatric comorbidities. Alterations in brain structure, synaptic development, and misregulation of neuroinflammation are considered risk factors for ASD and neuropsychiatric comorbidities. Electroencephalography has been developed to quantitatively explore effects of these neuronal changes of the brain in ASD. The pineal neurohormone melatonin is able to contribute to neural development. Also, this hormone has an inflammation-regulatory role and acts as a circadian key regulator to normalize sleep. These functions of melatonin may play crucial roles in the alleviation of ASD and its neuropsychiatric comorbidities. In this context, this article focuses on the presumable role of melatonin and suggests that this hormone could be a therapeutic agent for ASD and its related neuropsychiatric disorders.


Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2024
Author(s):  
Valentina Bieneck ◽  
Anke Bletsch ◽  
Caroline Mann ◽  
Tim Schäfer ◽  
Hanna Seelemeyer ◽  
...  

The neuroanatomy of autism spectrum disorder (ASD) shows highly heterogeneous developmental trajectories across individuals. Mapping atypical brain development onto clinical phenotypes, and establishing their molecular underpinnings, is therefore crucial for patient stratification and subtyping. In this longitudinal study we examined intra- and inter-individual differences in the developmental trajectory of cortical thickness (CT) in childhood and adolescence, and their genomic underpinnings, in 33 individuals with ASD and 37 typically developing controls (aged 11–18 years). Moreover, we aimed to link regional atypical CT development to intra-individual variations in restricted and repetitive behavior (RRB) over a two-year time period. Individuals with ASD showed significantly reduced cortical thinning in several of the brain regions functionally related to wider autism symptoms and traits (e.g., fronto-temporal and cingulate cortices). The spatial patterns of the neuroanatomical differences in CT were enriched for genes known to be associated with ASD at a genetic and transcriptomic level. Further, intra-individual differences in CT correlated with within-subject variability in the severity of RRBs. Our findings represent an important step towards characterizing the neuroanatomical underpinnings of ASD across development based upon measures of CT. Moreover, our findings provide important novel insights into the link between microscopic and macroscopic pathology in ASD, as well as their relationship with different clinical ASD phenotypes.


Autism ◽  
2017 ◽  
Vol 22 (6) ◽  
pp. 712-727 ◽  
Author(s):  
Lize De Coster ◽  
Jan R Wiersema ◽  
Eliane Deschrijver ◽  
Marcel Brass

Autism spectrum disorder is a neurodevelopmental disorder that is associated with problems in empathy. Recent research suggests that impaired control over self–other overlap based on motor representations in individuals with autism spectrum disorder might underlie these difficulties. In order to investigate the relationship of self–other distinction and empathy for pain in high-functioning autism and matched controls, we manipulated self–other distinction by using a paradigm in which participants are either imitated or not by a hand on a computer screen. A strong pain stimulus is then inflicted on the observed hand. Behavioral and physiological results in this study showed that overall affective responses while watching pain movies were the same in adults with high-functioning autism as in controls. Furthermore, controls showed higher affective responding after being imitated during the whole experiment, replicating previous studies. Adults with high-functioning autism, however, showed increased empathic responses over time after being imitated. Further exploratory analyses suggested that while affective responding was initially lower after being imitated compared to not being imitated, affective responding in the latter part of the experiment was higher after being imitated. These results shed new light on empathic abilities in high-functioning autism and on the role of control over self–other representational sharing.


2021 ◽  
pp. 332-351
Author(s):  
Saashi A. Bedford ◽  
Michelle Hunsche ◽  
Connor M. Kerns

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and, similar to obsessive-compulsive disorder (OCD), restricted and repetitive behaviors. The restricted, repetitive patterns of behaviors and interests that are characteristic of ASD often resemble the obsessions and compulsions of OCD, which can make it difficult to distinguish or differentiate the two conditions. A common challenge in diagnosing comorbid ASD and OCD is the apparent overlap in symptoms between the two disorders. This chapter discusses the differentiation between OCD and ASD, the assessment and diagnosis of OCD within the context of ASD, and the treatment of this presentation of OCD.


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