Predicting autism at birth

Steinman, Gary

doi:10.1016/j.mehy.2013.03.034

Cited by 13 publications

(9 citation statements)

References 46 publications

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“…Myelin integrity is crucial for functional neuro-circuitry and perturbations in myelin either during or after neuronal development leads to neurological deficits [78]. The findings are consistent with reports of abnormal myelination in BA10 of SZ, BD [79], and ASD patients [71,80]. Interestingly, effects on glutamate signalling have already been linked to oligodendrocyte dysfunction.…”

Section: Discussionsupporting

confidence: 73%

“…At the circulatory level, IGF-I promotes cell differentiation and growth and may also function as an anti-apoptotic agent [66]. Lower levels of IGF-1 have been found in serum of antipsychotic-naive [67] and antipsychotic-treated SZ patients [68], as well as in children with ASD [69-71]. A recent study reported a relationship between negative symptoms and IGF-1 plasma levels in first episode SZ [72].…”

Section: Discussionmentioning

confidence: 99%

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Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

et al. 2014

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BackgroundOver the last decade, the transgenic N-methyl-D-aspartate receptor (NMDAR) NR1-knockdown mouse (NR1neo−/−) has been investigated as a glutamate hypofunction model for schizophrenia. Recent research has now revealed that the model also recapitulates cognitive and negative symptoms in the continuum of other psychiatric diseases, particularly autism spectrum disorders (ASD). As previous studies have mostly focussed on behavioural readouts, a molecular characterisation of this model will help to identify novel biomarkers or potential drug targets.MethodsHere, we have used multiplex immunoassay analyses to investigate peripheral analyte alterations in serum of NR1neo−/− mice, as well as a combination of shotgun label-free liquid chromatography mass spectrometry, bioinformatic pathway analyses, and a shotgun-based 40-plex selected reaction monitoring (SRM) assay to investigate altered molecular pathways in the frontal cortex and hippocampus. All findings were cross compared to identify translatable findings between the brain and periphery.ResultsMultiplex immunoassay profiling led to identification of 29 analytes that were significantly altered in sera of NR1neo−/− mice. The highest magnitude changes were found for neurotrophic factors (VEGFA, EGF, IGF-1), apolipoprotein A1, and fibrinogen. We also found decreased levels of several chemokines. Following this, LC-MSE profiling led to identification of 48 significantly changed proteins in the frontal cortex and 41 in the hippocampus. In particular, MARCS, the mitochondrial pyruvate kinase, and CamKII-alpha were affected. Based on the combination of protein set enrichment and bioinformatic pathway analysis, we designed orthogonal SRM-assays which validated the abnormalities of proteins involved in synaptic long-term potentiation, myelination, and the ERK-signalling pathway in both brain regions. In contrast, increased levels of proteins involved in neurotransmitter metabolism and release were found only in the frontal cortex and abnormalities of proteins involved in the purinergic system were found exclusively in the hippocampus.ConclusionsTaken together, this multi-platform profiling study has identified peripheral changes which are potentially linked to central alterations in synaptic plasticity and neuronal function associated with NMDAR-NR1 hypofunction. Therefore, the reported proteomic changes may be useful as translational biomarkers in human and rodent model drug discovery efforts.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

et al. 2014

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“…In contrast, decreased histidine levels were not significant in children with poor neurodevelopment and low dioxin exposure compared to well-developed children exposed to low dioxin levels, suggesting that poor development itself is not a primary factor contributing to altered histidine metabolism. These results suggest that alterations of urinary histidine and tryptophan are specific to neurodevelopmental deficits resulting from dioxin exposure before and after birth when neurogenesis, especially myelination, continues [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Urinary Amino Acid Alterations in 3-Year-Old Children with Neurodevelopmental Effects due to Perinatal Dioxin Exposure in Vietnam: A Nested Case-Control Study for Neurobiomarker Discovery

et al. 2015

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In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity.

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“…Two additional serum parameters involved in neurogenesis often increased in cases of autism are serotonin and anti-myelin basic protein (MBP) 34 . One reported cause of decreased IGF is gene polymorphism.…”

Section: Igf As a Biomarkermentioning

confidence: 99%

The proposed role of insulin-like growth factor-1 in autism: A review

Steinman¹

2013

OA Autism

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Predicting autism at birth

Cited by 13 publications

References 46 publications

Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

Urinary Amino Acid Alterations in 3-Year-Old Children with Neurodevelopmental Effects due to Perinatal Dioxin Exposure in Vietnam: A Nested Case-Control Study for Neurobiomarker Discovery

The proposed role of insulin-like growth factor-1 in autism: A review

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