scholarly journals N-Methyl-d-aspartate (NMDA) receptor antibody in relation to autism spectrum disorder (ASD): presence and association with symptom profile

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Heba Hamed Elshahawi ◽  
Ghada Refaat Amin Taha ◽  
Hanan Mohamed Ezzeldin Azzam ◽  
Reem H. El Ghamry ◽  
Ahmed Adel Mohammad Abdelgawad ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Nmda Receptor ◽  
Autoimmune Encephalitis ◽  
Stereotyped Behavior ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Spectrum Disorder ◽  
Symptom Profile ◽  
Stereotyped Behaviors ◽  
Autistic Regression

Abstract Background Several studies pointed to immune dysregulation abnormalities linked to autism spectrum disorders (ASD). Of those, several autoantibodies had been identified. Recent findings of N-methyl d-aspartate (NMDA) antibodies in autoimmune encephalitis suggested that it caused symptoms like autistic regression. Thus, the purpose of the study was to test for the presence of anti-NMDAR antibodies in the ASD disorder population and to correlate this with the clinical findings. Results Eighty-seven autistic children, 4–12 years old, were enrolled in the study and were matched with sixty typically developing children used as controls. The diagnosis of cases was confirmed by ADOS-2 and clinical evaluation. None of the control children had positive anti-NMDAR antibodies, while 26.4% (23 children) of the patients’ group were positive for serum anti-NMDA receptor antibodies (> 200 pg/ml, p = 0.0157). The positive anti-NMDAR antibody was statistically correlated with better speech stage (p = 0.017), more severe stereotyped behavior (p ≤ 0.001), and abnormal EEG findings (p = 0.025). Conclusions There is a possibility of the presence of anti-NMDAR antibodies in the autism spectrum disorder population with certain characteristics, especially the severity of the stereotyped behaviors.

scholarly journals Examination of Stimulus Over-Selectivity in Children With Autism Spectrum Disorder and Its Relationship to Stereotyped Behaviors and Cognitive Flexibility

2020 ◽  
pp. 108835762094350
Author(s):  
M. P. Kelly ◽  
P. Reed
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Flexibility ◽  
Behavioral Interventions ◽  
Stereotyped Behavior ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Typically Developing ◽  
Mental Age ◽  
Stereotyped Behaviors ◽  
Relationship Of

Stimulus over-selectivity describes a phenomenon in which an individual responds only to a subset of the stimuli present in the environment and, thus, may restrict learning. This study aimed to develop understanding of the nature and role of over-selectivity in autism spectrum disorder (ASD) by analyzing the relationship of over-selectivity to core deficits of ASD: stereotyped responding and inflexibility. Over-selectivity was investigated in a visual discrimination task in 24 children, 12 diagnosed with ASD and 12 mental-age-matched typically developing children. In addition, the participants’ levels of intellectual functioning, stereotypy, and cognitive flexibility were assessed using established tools. Results showed that over-selectivity was associated with IQ and stereotyped behavior but was not related to levels of cognitive flexibility nor did cognitive flexibility significantly correlate with stereotyped behavior in individuals with ASD. The current findings require consideration when designing behavioral interventions for individuals with ASD.

The Dopamine Hypothesis of Autism Spectrum Disorder Revisited: Current Status and Future Prospects

2021 ◽  
pp. 1-11
Author(s):  
Denis Pavăl ◽  
Ioana Valentina Micluția
Keyword(s):  
Autism Spectrum Disorder ◽  
Dopaminergic System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Current Status ◽  
Social Deficits ◽  
Future Prospects ◽  
Autistic Behavior ◽  
Stereotyped Behaviors ◽  
Dopamine Hypothesis

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. Despite intensive research, its etiopathogenesis remains largely unclear. Although studies consistently reported dopaminergic anomalies, a coherent dopaminergic model of ASD was lacking until recently. In 2017, we provided a theoretical framework for a “dopamine hypothesis of ASD” which proposed that autistic behavior arises from a dysfunctional midbrain dopaminergic system. Namely, we hypothesized that malfunction of 2 critical circuits originating in the midbrain, that is, the mesocorticolimbic and nigrostriatal pathways, generates the core behavioral features of ASD. Moreover, we provided key predictions of our model along with testing means. Since then, a notable number of studies referenced our work and numerous others provided support for our model. To account for these developments, we review all these recent data and discuss their implications. Furthermore, in the light of these new insights, we further refine and reconceptualize our model, debating on the possibility that various etiologies of ASD converge upon a dysfunctional midbrain dopaminergic system. In addition, we discuss future prospects, providing new means of testing our hypothesis, as well as its limitations. Along these lines, we aimed to provide a model which, if confirmed, could provide a better understanding of the etiopathogenesis of ASD along with new therapeutic strategies.

scholarly journals Clinical and autoimmune features of a patient with autism spectrum disorder seropositive for anti—NMDA-receptor autoantibody

2017 ◽  
Vol 19 (1) ◽  
pp. 65-70 ◽  
Keyword(s):  
Autism Spectrum Disorder ◽  
Nmda Receptor ◽  
Single Molecule ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Psychotic Symptoms ◽  
Direct Role ◽  
Major Depressive Episodes ◽  
Depressive Episodes

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are involved in ASD remains an open question. Here, we identified within a cohort an ASD patient with multiple circulating autoantibodies, including the well-characterized one against glutamate NMDA receptor (NMDAR-Ab). The patient exhibited alexithymia and previously suffered from two major depressive episodes without psychotic symptoms. Using a single molecule-based imaging approach, we demonstrate that neither NMDAR-Ab type G immunoglobulin purified from the ASD patient serum, nor that from a seropositive healthy subject, disorganize membrane NMDAR complexes at synapses. These findings suggest that the autistic patient NMDAR-Abs do not play a direct role in the etiology of ASD and that other autoantibodies directed against neuronal targets should be investigated.

scholarly journals Autoimmune Encephalitis and Autism Spectrum Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Paul Whiteley ◽  
Ben Marlow ◽  
Ritika R. Kapoor ◽  
Natasa Blagojevic-Stokic ◽  
Regina Sala
Keyword(s):  
Autism Spectrum Disorder ◽  
Autoimmune Encephalitis ◽  
Preliminary Evidence ◽  
Autism Spectrum ◽  
Elevated Risk ◽  
Spectrum Disorder ◽  
Brain Inflammation ◽  
Brain Cells ◽  
Herpes Encephalitis ◽  
Autoimmune Psychosis

The concept of “acquired autism” refers to the hypothesis that amongst the massive heterogeneity that encompasses autism spectrum disorder (ASD) there may be several phenotypes that are neither syndromic nor innate. Strong and consistent evidence has linked exposure to various pharmacological and infective agents with an elevated risk of a diagnosis of ASD including maternal valproate use, rubella and herpes encephalitis. Autoimmune encephalitis (AE) describes a group of conditions characterised by the body's immune system mounting an attack on healthy brain cells causing brain inflammation. The resultant cognitive, psychiatric and neurological symptoms that follow AE have also included ASD or autism-like traits and states. We review the current literature on AE and ASD. Drawing also on associated literature on autoimmune psychosis (AP) and preliminary evidence of a psychosis-linked subtype of ASD, we conclude that AE may either act as a potentially causative agent for ASD, and/or produce symptoms that could easily be mistaken for or misdiagnosed as autism. Further studies are required to discern the connection between AE and autism. Where autism is accompanied by regression and atypical onset patterns, it may be prudent to investigate whether a differential diagnosis of AE would be more appropriate.

scholarly journals A Ketogenic Diet and the Treatment of Autism Spectrum Disorder

2021 ◽  
Vol 9 ◽  
Author(s):  
Qinrui Li ◽  
Jingjing Liang ◽  
Na Fu ◽  
Ying Han ◽  
Jiong Qin
Keyword(s):  
Autism Spectrum Disorder ◽  
Ketogenic Diet ◽  
Mammalian Target Of Rapamycin ◽  
Stereotyped Behavior ◽  
Autism Spectrum ◽  
The Body ◽  
Spectrum Disorder ◽  
Brain Diseases ◽  
Low Carbohydrate Diet ◽  
Underlying Mechanisms

Autism spectrum disorder (ASD) is characterized by stereotyped behavior and deficits in communication and social interaction. There are no curative treatments for children with ASD. The ketogenic diet (KD) is a high-fat, appropriate-protein, and low-carbohydrate diet that mimics the fasting state of the body and is proven beneficial in drug-resistant epilepsy and some other brain diseases. An increasing number of studies demonstrated that a KD improved autistic behavior, but the underlying mechanisms are not known. We reviewed the neuroprotective role of a KD in ASD, which is likely mediated via improvements in energy metabolism, reductions in antioxidative stress levels, control of neurotransmitters, inhibition of the mammalian target of rapamycin (mTOR) signaling pathway, and modulation of the gut microbiota. A KD is likely a safe and effective treatment for ASD.

scholarly journals Anti-NMDA Receptor Encephalitis in a Patient with a History of Autism Spectrum Disorder

2020 ◽  
Vol 10 (3) ◽  
pp. 231-235
Author(s):  
Xavier Diao ◽  
Milana Mor
Keyword(s):  
Autism Spectrum Disorder ◽  
Nmda Receptor ◽  
Neuropsychiatric Symptoms ◽  
Antipsychotic Agents ◽  
Altered Mental Status ◽  
Autism Spectrum ◽  
Acute Onset ◽  
Spectrum Disorder ◽  
Nmda Receptor Encephalitis ◽  
History Of

Background: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune syndrome characterized by a well-described constellation of neuropsychiatric symptoms. Its exact pathophysiology is poorly understood, but it is thought to be mediated by autoantibodies against NMDA (N-methyl-D-aspartate)-type glutamate receptors in the central nervous system. There is ongoing literature to suggest that patients with autism spectrum disorder (ASD) have evidence of neuroinflammation—or by definition, encephalitis. Objective: To investigate the link between autism spectrum disorder and autoimmune encephalitides. Methods: We present a case of anti-NMDA receptor encephalitis in a patient with autism spectrum disorder. “OP” is a 16-year-old male with a history of attention-deficit/ hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) who presented with a 3-day history of acute-onset altered mental status, electroencephalogram (EEG)-corroborated seizures, and slurred speech. Laboratory studies were significant for serum- and cerebrospinal fluid (CSF)-positive NMDA antibodies. The child psychiatry consult-liaison service was consulted for significant agitation and behavioral dyscontrol. We recommended 1:1 observation for safety, as well as antipsychotic agents titrated to clinical effect. The patient had a protracted hospital course, but was eventually discharged to an acute rehabilitation facility for continued stabilization and therapy. Conclusion: It remains to be seen if the relation between encephalitis and ASD is uni- or bidirectional, that is: whether children with ASD have a genetic diathesis to developing encephalitides (such as those mediated by the NMDAR), or conversely, if deranged or inflamed neuroreceptor processes are implicated in the development of ASD.

A Dopamine Hypothesis of Autism Spectrum Disorder

2017 ◽  
Vol 39 (5) ◽  
pp. 355-360 ◽  
Author(s):  
Denis Pavăl
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Dopamine Antagonists ◽  
Social Deficits ◽  
Autistic Behavior ◽  
Stereotyped Behaviors ◽  
Dopamine Hypothesis ◽  
Dopamine Signaling ◽  
Neuroreceptor Imaging

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis.

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