Medial Frontal Lobe Neurochemistry in Autism Spectrum Disorder is Marked by Reduced N-Acetylaspartate and Unchanged Gamma-Aminobutyric Acid and Glutamate + Glutamine Levels

Pereira, Alexandre Libório Dias; Violante, Inês R.; Mouga, Susana; Oliveira, Guiomar; Castelo‐Branco, Miguel

doi:10.1007/s10803-017-3406-8

Cited by 24 publications

(37 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, higher SRS‐2 scores (indicative of greater ASD symptomatology) were associated with reduced concentrations of GABA+ in the VIS. This finding is consistent with previous findings linking reductions in GABA to increases in ASD symptoms [Brix et al, ; Carvalho Pereira et al, ]. However, in light of the inverse relationship between VIS GABA+ and VST performance, this result appears to be conflicting, especially given that prior reports have shown that faster, more efficient search is related to ASD symptom severity [Joseph et al, ; Keehn et al, ].…”

Section: Discussionsupporting

confidence: 89%

“…While GABA+ levels did not differ between groups, results from the present study did show significant differences in other neurochemical concentrations (NAA, tCr, and Glx) between ASD and TD in the rTPJ. In children with ASD, NAA has been found to be lower in various regions of the cortex [Carvalho Pereira et al, 2018;Harada et al, 2011;Kleinhans, Schweinsburg, Cohen, Müller, & Courchesne, 2007;Kubas et al, 2012]. NAA is a neuronal marker representing neurodysfunction or neuronal loss [de Graaf, 2018].…”

Section: Differences In Neurochemical Concentrations In the Rtpjmentioning

confidence: 99%

“…Finally, VIS was chosen to determine whether superior search in ASD is associated with enhanced discrimination [O'Riordan & Plaisted, ], as occipital GABA levels are associated with orientation perceptual thresholds [Edden et al, ; Song et al, ]. Finally, because others have hypothesized that an E/I imbalance may contribute to the development of ASD [Hussman, ; Rubenstein & Merzenich, ], and prior findings have shown an association between GABA and ASD symptom severity [Brix et al, ; Carvalho Pereira, Violante, Mouga, Oliveira, & Castelo‐Branco, ] we examined the relationship between GABA levels and measures of ASD symptomatology.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

et al. 2020

View full text Add to dashboard Cite

Although diagnosed on the basis of deficits in social communication and interaction, autism spectrum disorder (ASD) is also characterized by superior performance on a variety of visuospatial tasks, including visual search. In neurotypical individuals, region‐specific concentrations of the inhibitory neurotransmitter gamma‐aminobutyric acid (GABA) are associated with individual differences in attention and perception. While it has been hypothesized that ASD may be associated with an excitatory–inhibitory imbalance, it remains unclear how this may contribute to accelerated visual search performance in individuals with ASD. To investigate this, 21 children with ASD and 20 typically developing children participated in a visual search task and a magnetic resonance spectroscopy study to detect neurochemical concentrations, including GABA. Region‐specific neurochemicals were examined in the right frontal eye fields, right temporal–parietal junction (rTPJ), and bilateral visual cortex (VIS). GABA concentrations did not differ between groups; however, in children with ASD, greater GABA concentration in the VIS was related to more efficient search. Additionally, lower VIS GABA levels were also associated with increased social impairment. Finally, we found reduced N‐acetyl aspartate, total creatine, glutamate and glutamine (Glx), GABA/Glx in the rTPJ, suggestive of neuronal dysfunction in a critical network hub. Our results show that GABA concentrations in the VIS are related to efficient search in ASD, thus providing further evidence of enhanced discrimination in ASD. Autism Res 2020, 13: 550–562. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Children with autism spectrum disorder (ASD) often perform better than their non‐ASD peers on visual search tasks; however, it is unclear how they achieve this superior performance. Using magnetic resonance spectroscopy to measure neurochemicals in the brain, we found that the level of one, gamma‐aminobutyric acid, in the visual cortex was directly related to search abilities in children with ASD. These results suggest that faster search may relate to enhanced perceptual functioning in children with ASD.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Differences In Neurochemical Concentrations In the Rtpjmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Neuroinflammation may explain the dysregulation between GABA and Glutamate cortical neurocircuitry in ASD children, particularly in the frontostriatal system with functional network topology (Cerame et al, 2008 ; Jakab et al, 2013 ; Carvalho Pereira et al, 2017 ; Naaijen et al, 2017 ; Nardone et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

et al. 2018

View full text Add to dashboard Cite

Autism spectrum disorders (ASD) is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012). Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B) in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR), heart rate variability (HRV), body temperature, and galvanic skin response (GSR), may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.

show abstract

“…To begin to identify the molecular etiology of aberrant social and repetitive behaviors caused by increased β-cat in our mice, we employed unbiased next-generation sequencing of RNA from the prefrontal cortex (PFC)-a brain region associated with social behavior and implicated in ASD in human studies (Hashemi et al, 2017;Selimbeyoglu et al, 2017;Brumback et al, 2018;Carvalho Pereira et al, 2018;Lazaro et al, 2019). We compared mice with elevated β-cat and altered social and repetitive behaviors (β-cat cOEs, APC cKOs), mice with reduced β-cat that do not display the phenotypes (APC/βcat cKOs) and control littermates.…”

Section: Elevated β-Cat Causes Altered Expression Of Several Genes LImentioning

confidence: 99%

Excessive β-Catenin in Excitatory Neurons Results in Reduced Social and Increased Repetitive Behaviors and Altered Expression of Multiple Genes Linked to Human Autism

Alexander

Pirone

Jacob

2020

Front. Synaptic Neurosci.

View full text Add to dashboard Cite

Multiple human autism risk genes are predicted to converge on the β-catenin (β-cat)/Wnt pathway. However, direct tests to link β-cat up-or down-regulation with autism are largely lacking, and the associated pathophysiological changes are poorly defined. Here we identify excessive β-cat as a risk factor that causes expression changes in several genes relevant to human autism. Our studies utilize mouse lines with β-cat dysregulation in forebrain excitatory neurons, identified as cell types with a convergent expression of autism-linked genes in both human and mouse brains. We show that mice expressing excessive β-cat display behavioral and molecular changes, including decreased social interest, increased repetitive behaviors, reduced parvalbumin and altered expression levels of additional genes identified as potential risk factors for human autism. These behavioral and molecular phenotypes are averted by reducing β-cat in neurons predisposed by gene mutations to express elevated β-cat. Using next-generation sequencing of the prefrontal cortex (PFC), we identify 87 dysregulated genes that are shared between mouse lines with excessive β-cat and autism-like behaviors, but not mouse lines with reduced β-cat and normal social behavior. Our findings provide critical new insights into β-cat, Wnt pathway dysregulation in the brain causing behavioral phenotypes relevant to the disease and the molecular etiology which includes several human autism risk genes.

show abstract

Medial Frontal Lobe Neurochemistry in Autism Spectrum Disorder is Marked by Reduced N-Acetylaspartate and Unchanged Gamma-Aminobutyric Acid and Glutamate + Glutamine Levels

Cited by 24 publications

References 104 publications

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

A Magnetic Resonance Spectroscopy Study of Superior Visual Search Abilities in Children with Autism Spectrum Disorder

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

Excessive β-Catenin in Excitatory Neurons Results in Reduced Social and Increased Repetitive Behaviors and Altered Expression of Multiple Genes Linked to Human Autism

Contact Info

Product

Resources

About