A Comprehensive Review of the 1H-MRS Metabolite Spectrum in Autism Spectrum Disorder

Ford, Talitha C.; Crewther, David P.

doi:10.3389/fnmol.2016.00014

Cited by 94 publications

(108 citation statements)

References 134 publications

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“…Another study detected reduced neuronal firing in iPSCderived neurons of eight individuals with idiopathic ASD (Marchetto et al, 2017) and detected a correlation of reduced network complexity to behavioral and cognitive phenotype of the donors (Amatya et al, 2019). Moreover, reduced GABA concentration, as seen in the ASDCASK_SS brain was reported in groups of children with ASD (Ford and Crewther, 2016).…”

Section: Cask-related Disorders Have Emerged As An Important Genetic mentioning

confidence: 92%

Presynaptic dysfunction inCASK-related neurodevelopmental disorders

Becker

Mastropasqua

Reising

et al. 2019

Preprint

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HighlightsModelling of CASK-related disorders using iPSC-derived human neuronal cells CASK mutations cause dysregulation of its protein interactor partners Reduced CASK levels primarily affect inhibitory presynapse development In vitro GABAergic phenotype predicts in vivo neurotransmitter levels Summary (150 words)CASK-related disorders are a genetically defined group of neurodevelopmental syndromes.There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK mutation consequences and neuronal level effects using induced pluripotent stem cell-derived neurons from two mutation carriers; one male diagnosed with ASD and a female with MICPCH. We show a reduction of the CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of gene sets involved in presynaptic development and CASK protein interactors. Furthermore, CASKdeficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory-inhibitory (E/I) balance in developing neural circuitries. Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in brain. Our data shows that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments for CASK-related disorders.

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Section: Cask-related Disorders Have Emerged As An Important Genetic mentioning

confidence: 92%

Presynaptic dysfunction inCASK-related neurodevelopmental disorders

Becker

Mastropasqua

Reising

et al. 2019

Preprint

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“…106 A systematic review found reduced absolute levels of subcortical N-acetylaspartate and creatine along with phosphocreatine. 107 Other notable findings were increased creatine, phosphocreatine, glutamate, N-acetylaspartate, and myoinositol in the cortical white matter. In addition, the gray matter had elevated creatine, phosphocreatine, glutamate, N-acetylaspartate, and choline.…”

Section: High-angular-resolution Diffusion Imagingmentioning

confidence: 97%

“…A meta‐analysis of 22 studies with a total of 632 typically developing individuals and 844 individuals with ASD found significantly lower N ‐acetylaspartate levels in the frontal regions of the ASD group . A systematic review found reduced absolute levels of subcortical N ‐acetylaspartate and creatine along with phosphocreatine . Other notable findings were increased creatine, phosphocreatine, glutamate, N ‐acetylaspartate, and myoinositol in the cortical white matter.…”

Section: Neurobiology Of Asdmentioning

confidence: 99%

“…Other notable findings were increased creatine, phosphocreatine, glutamate, N ‐acetylaspartate, and myoinositol in the cortical white matter. In addition, the gray matter had elevated creatine, phosphocreatine, glutamate, N ‐acetylaspartate, and choline …”

Section: Neurobiology Of Asdmentioning

confidence: 99%

“…In addition, the gray matter had elevated creatine, phosphocreatine, glutamate, N-acetylaspartate, and choline. 107 Neuroelectrophysiology Cortical connectivity can be assessed with electrophysiological studies. Early joint attention is the ability to coordinate visual attention with another person.…”

Section: High-angular-resolution Diffusion Imagingmentioning

confidence: 99%

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Autism spectrum disorder: Trends in research exploring etiopathogenesis

Gyawali

Patra

2019

Psychiatry Clin Neurosci

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Autism spectrum disorder is a neurodevelopmental condition in which affected individuals have difficulties while interacting and communicating socially, and repetitive behaviors. It has a multifactorial etiology. Various risk factors, including genetic and environmental influences, have been explored while trying to understand its causation. As older evidence was suggestive of a high heritability, a majority of research focused on finding the underlying genetic causes of autism. Due to these efforts, there have been advances in the knowledge of some of the genetic factors associated with autism. But a recent trend also shows an increasing interest in exploration of various potential environmental triggers. These efforts have brought us closer to understanding the elusive disorder more so than ever before. The current review discusses the recent trends in research exploring the etiopathogenesis of autism spectrum disorder.

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Reduced GABA and altered somatosensory function in children with autism spectrum disorder

et al. 2016

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Background Abnormal responses to tactile stimuli are a common feature of Autism Spectrum Disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children. Methods GABA-edited MRS was acquired in 37 children with Autism and 35 Typically Developing Children from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured. Results Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism. Conclusions GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies.

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A Comprehensive Review of the 1H-MRS Metabolite Spectrum in Autism Spectrum Disorder

Cited by 94 publications

References 134 publications

Presynaptic dysfunction inCASK-related neurodevelopmental disorders

Presynaptic dysfunction inCASK-related neurodevelopmental disorders

Autism spectrum disorder: Trends in research exploring etiopathogenesis

Reduced GABA and altered somatosensory function in children with autism spectrum disorder

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