Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders

Ormstad, Heidi; Bryn, Vesna; Verkerk, Robert; Skjeldal, Ola H.; Halvorsen, Bente; Saugstad, Ola Didrik; Isaksen, Jørn; Maes, Michaël

doi:10.2174/1871527317666180720163221

Cited by 33 publications

(28 citation statements)

References 63 publications

(72 reference statements)

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“…Lower tryptophan and KA levels differentially characterize childhood autism and intellectual disability disorder from Asperger’s syndrome that, instead, is marked by elevated tryptophan and lower 5-HT synthesis [ 135 ].…”

Section: The Kynurenines Pathwaymentioning

confidence: 99%

Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway

et al. 2020

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Autism Spectrum Disorder (ASD) etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and the Kynurenine pathway; here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies have also identified some important polymorphisms in chromosome loci related to the human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates the Kynurenine pathway with an increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in the glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of the Kynurenine branch induces depletion of melatonin and serotonin, worsening ASD symptoms. Thus, in genetically predisposed subjects, aberrant neurodevelopment may derive from a complex interplay between inflammatory processes, mitochondrial dysfunction, oxidative stress and Kynurenine pathway overexpression. To validate this hypothesis a new translational research approach is necessary.

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Section: The Kynurenines Pathwaymentioning

confidence: 99%

Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway

et al. 2020

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“…More recent study provided evidence of abnormalities in brain volume of IgG-ASD children and rhesus monkeys (41,42). Cytokines regulate brain activity through the brain's gut axis, for instance, high-level brain-derived neurotrophic factor (BDNF), and low-level tryptophan and kynurenic acid were characteristics of ASD, abnormal EEG results were associated with an elevated BDNF/PRO-BDNF ratio (43). The elevation of IL-6 in the brain could involve in the mediation of autism-like behaviors through impairments of neuroanatomical structures and neuronal plasticity (44).…”

Section: Discussionmentioning

confidence: 99%

Study on Aberrant Eating Behaviors, Food Intolerance, and Stereotyped Behaviors in Autism Spectrum Disorder

Liu

Fang

et al. 2020

Front. Psychiatry

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Objective: To investigate the aberrant eating behaviors (EBs), gastrointestinal (GI) symptoms, and food intolerance in children with autism spectrum disorder (ASD) and their association with clinical core symptoms of ASD. Method: A total of 94 preschool children with ASD treated at the Child Mental Health Research Center of Nanjing Brain Hospital between October 2016 and April 2018 were enrolled. In addition, 90 children with typical development (TD) in the community during the same period were recruited. The conditions of aberrant EBs and GI symptoms in children were investigated using questionnaire surveys. Serum specific IgG antibodies against 14 kinds of food were detected using enzyme-linked immunosorbent assays (ELISAs). Results: The detection rate of aberrant EBs in the ASD group was significantly higher than that in the TD group (67.39 vs. 34.94%), and the rate of GI symptoms was also higher in the ASD group than that in the TD group (80.22 vs. 42.11%). Detection of food intolerance in children with ASD showed that the positive rate was 89.89% and that the majority of children had multiple food intolerances. The correlation analysis results showed that the severity of aberrant EBs positively correlated with stereotyped behavior of children with ASD (r = 0.21, P = 0.04) and that food-specific IgG antibodies concentrations positively correlated with high-level stereotyped behavior in children with ASD (r = 0.23, P = 0.03). Conclusion: ASD with aberrant EBs or high food-specific IgG antibodies concentrations had more severe stereotyped behavior, which may have implications for exploring the immune mechanism of ASD. Clinical Trial Registration: ChiCTR-RPC-16008139.

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“…Abnormality of tryptophan metabolism in patients with ASD has been reported in multiple studies, which was characterized by decreased concentrations of tryptophan [33] and increased levels of serotonin in blood [11]. In the gut, there are three main tryptophan metabolism pathways leading to serotonin, kynurenine, and indole derivatives [34] [35].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Gut Vitamins and Amino Acids Metabolism are Associated with Symptoms and Neurodevelopment of Children with Autism Spectrum Disorders

Zhu

Hua

Yang

et al. 2020

Preprint

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Background Accumulated evidence have supported metabolic disturbance may be associated with the pathogenesis of autism spectrum disorders (ASD). Despite abnormalities of some shared metabolic pathways, specific differential compounds are inconsistent in studies, which made a challenge to elucidate the role of metabolism in the mechanism of ASD. Besides, few researches have assessed the correlation between gut metabolites with symptoms of ASD. Objectives The present study aimed to evaluate the gut metabolomic profiles of children with ASD and to analyze potential interaction between gut metabolites with symptoms and neurodevelopment of ASD children. Methods In this cross-sectional case-control study, 120 aged 2–6 years ASD children and 60 sex and age matched typically developing (TD) children were included. Autistic symptoms were assessed with the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and the Social Responsiveness Scale (SRS). Neurodevelopment was assessed with the Gesell Developmental Scale (GDS). Fecal samples were analyzed by untargeted liquid chromatography-mass spectrometry (LC-MS) methods, then systematic bioinformatic analyses were performed to characterize the gut metabolomic profiles of ASD and TD children. The correlations between metabolites and clinical assessment scores were assessed using Spearman correlation. Results ASD children exhibit gut metabolism perturbation compared with TD children. A total of 96 differential metabolites between the ASD and TD groups were identified, with 35 increased and 61 decreased in ASD group. The metabolic disturbance of ASD involved in multiple vitamins and amino acids metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine and methionine metabolism, and vitamin digestion and absorption. The imbalanced gut metabolites are significantly correlated to symptoms and neurodevelopment of ASD children. Limitations This cross-sectional study revealed a correlation, but do not allow to prove causation of symptoms and gut metabolites outcome. The disease specificity of the metabolomic disturbance need to be evaluated in future studies.Conclusions ASD children have altered gut metabolite profiles compared with TD children, which mainly involved in multiple vitamins and amino acids metabolism pathways. Notably, vitamins metabolism abnormalities may play roles in the disturbance of amino acids metabolism. Imbalanced gut metabolites are related to symptoms and neurodevelopment of ASD children. Our findings provided an improved understanding of perturbations of metabolome networks in ASD.

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Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders

Cited by 33 publications

References 63 publications

Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway

Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway

Study on Aberrant Eating Behaviors, Food Intolerance, and Stereotyped Behaviors in Autism Spectrum Disorder

Alterations in Gut Vitamins and Amino Acids Metabolism are Associated with Symptoms and Neurodevelopment of Children with Autism Spectrum Disorders

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