Amino Acid Dysregulation Metabotypes: Potential Biomarkers for Diagnosis and Individualized Treatment for Subtypes of Autism Spectrum Disorder
Authors: Elizabeth L R Donley
Alan M Smith
David G Amaral
Joseph J King
Michael A Ludwig
Paul R West
Robert E Burrier
Journal: Biological psychiatry (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Amino acids; Autism; Biomarker; Diagnosis; Metabolomics
Affiliations: Stemina Biomarker Discovery Inc., Madison, Wisconsin., The MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, California. Electronic address: .

Abstract:  Background: Autism spectrum disorder (ASD) is behaviorally and biologically heterogeneous and likely represents a series of conditions arising from different underlying genetic, metabolic, and environmental factors. There are currently no reliable diagnostic biomarkers for ASD. Based on evidence that dysregulation of branched-chain amino acids (BCAAs) may contribute to the behavioral characteristics of ASD, we tested whether dysregulation of amino acids (AAs) was a pervasive phenomenon in individuals with ASD. This is the first article to report results from the Children's Autism Metabolome Project (CAMP), a large-scale effort to define autism biomarkers based on metabolomic analyses of blood samples from young children. Methods: Dysregulation of AA metabolism was identified by comparing plasma metabolites from 516 children with ASD with those from 164 age-matched typically developing children recruited into the CAMP. ASD subjects were stratified into subpopulations based on shared metabolic phenotypes associated with BCAA dysregulation. Results: We identified groups of AAs with positive correlations that were, as a group, negatively correlated with BCAA levels in ASD. Imbalances between these two groups of AAs identified three ASD-associated amino acid dysregulation metabotypes. The combination of glutamine, glycine, and ornithine amino acid dysregulation metabotypes identified a dysregulation in AA/BCAA metabolism that is present in 16.7% of the CAMP subjects with ASD and is detectable with a specificity of 96.3% and a positive predictive value of 93.5% within the ASD subject cohort. Conclusions: Identification and utilization of metabotypes of ASD can lead to actionable metabolic tests that support early diagnosis and stratification for targeted therapeutic interventions. 

Retracted: No

PubPeer comments:
 Here. author Lotti and associates praise and summarise papers in other journals by author Lotti and associates. The  new paradigm of the title is in fact a very old one, the two-century-old belief system of Hahnemann s homeopathy, although the  succussion aspect of the classical homeopathic ritual (i.e. striking the mixing vessel with a leather-bound bible during the process of successive dilution) has been rebranded as  Sequential Kinetic Activation . * Barygina and coworkers (1) evaluated the effects of low dose SKA IL-4, IL-10, b-fibroblast growth factor (b-FGF), and b-endorphin in the modulation of intracellular and extracellular oxidative stress and on the viability of human perilesional keratinocytes obtained from skin biopsies of vitiligo patients. * Ref [1] is [Barygina et al (2015)] . In the relevant PubPeer thread I have raised concerns about the ethical use of human subjects, and the pecuniary question of  who paid for this study? . * In a retrospective spontaneous clinical study, Lotti and coworkers (2) described the positive results in vitiligo treatment with low dose SKA cytokines alone or in association with microphototherapy with positive percentage of skin repigmentation in a number of patients varying between 74 and 90% * Ref [2] is [Lotti et al (2015)] . I am unsure about the status of this supposed paper; there is a PubMed entry for it, but no trace of it in the publisher s website. It is purportedly part of a Special Issue of the journal which simply does not exist. * The availability of low dose SKA signaling molecules makes possible to use lower doses of activated molecules with therapeutic outcomes comparable to those induced by high dosages but without side effects (5). * Ref [5] is an advertisement for GUNA homeopathic products written by present author Lotti and the proprietor of the GUNA company, for a journal edited by Lotti, published by the parasitical company OMICS. https: pubpeer.com publications 12311B018337F8D6431D7BB60002BD ,