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Erythrocyte fatty acid profiles in children are not predictive of autism spectrum disorder status: a case control study.

ABSTRACT: Biomarkers promise biomolecular explanations as well as reliable diagnostics, stratification, and treatment strategies that have the potential to help mitigate the effects of disorders. While no reliable biomarker has yet been found for autism spectrum disorder (ASD), fatty acids have been investigated as potential biomarkers because of their association with brain development and neural functions. However, the ability of fatty acids to classify individuals with ASD from age/gender-matched neurotypical (NEU) peers has largely been ignored in favor of investigating population-level differences. Contrary to existing work, this classification task between ASD and NEU cohorts is the main focus of this work. The data presented herein suggest that fatty acids do not allow for classification at the individual level.

SUBMITTER: Howsmon DP

PROVIDER: S-EPMC5853097 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Erythrocyte fatty acid profiles in children are not predictive of autism spectrum disorder status: a case control study.

Howsmon Daniel P DP Adams James B JB Kruger Uwe U Geis Elizabeth E Gehn Eva E Hahn Juergen J

Biomarker research 20180314

Biomarkers promise biomolecular explanations as well as reliable diagnostics, stratification, and treatment strategies that have the potential to help mitigate the effects of disorders. While no reliable biomarker has yet been found for autism spectrum disorder (ASD), fatty acids have been investigated as potential biomarkers because of their association with brain development and neural functions. However, the ability of fatty acids to classify individuals with ASD from age/gender-matched neuro ...[more]

PMID: 29568526

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Project description:BackgroundThe pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group.MethodsA double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group.ResultsThere were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention.ConclusionSpanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT03620097].

Project description:Functional abilities in children with autism spectrum disorder (ASD) are highly heterogenous, and impairments can overlap with non-ASD neurodevelopmental disorders. We compared the profiles of children assessed for ASD with and without an ASD diagnosis using a retrospective cohort study of 101,739 children born in British Columbia (2000-2008). The children were grouped into the following five comparison groups: (1) ASD- (n = 1131), (2) ASD+ (n = 1583), (3) Ministry of Education designated ASD+ (n = 654), (4) special need other than ASD (n = 11,663), and (5) typically developing (n = 86,708). Five developmental domains were assessed using the Early Development Instrument. ANCOVA was used to control for covariates, Tukey's HSD test for multiple comparisons, and Cohen's d for effect size. The ASD- group had slightly higher scores than the ASD+ group with small to medium effect sizes in all domains (d = 0.20-0.48). The ASD- group had slightly higher scores than the Ministry of Education ASD+ group in only three domains with small effect sizes (d = 0.21-0.25). The ASD- group had lower scores in all domains compared to the typically developing group with large effect sizes in all domains (d = 1.12-1.77). The ASD- group received less education funding at school entry than both ASD+ groups. Overall, only small to medium differences in development were detected between the ASD- and ASD+ groups. While these children differ diagnostically, they share similar functional profiles and have substantially more difficulties than typically developing children. Therefore, differences in levels of support at school entry raise critical questions of equity. LAY SUMMARY: Comparison of children in British Columbia who have been referred for an autism assessment, with or without a diagnosis, shows similarities in their functional and developmental profiles in kindergarten. Furthermore, both groups of children have more difficulties than typically developing children. However, children who have been referred for assessment without an autism diagnosis receive less financial support at school entry, raising important questions on equity.

Project description:Sertraline is one among several selective serotonin reuptake inhibitors (SSRIs) that exhibited improvement of language development in Autism Spectrum Disorder (ASD); however, the molecular mechanism has not been elucidated. A double blind, randomized, 6-month, placebo-controlled, clinical trial of low-dose sertraline in children ages (3-6 years) with ASD was conducted at the UC Davis MIND Institute. It aimed at evaluating the efficacy and benefit with respect to early expressive language development and global clinical improvement. This study aimed to identify molecular biomarkers that might be key players in the serotonin pathway and might be predictive of a clinical response to sertraline. Fifty eight subjects with the diagnosis of ASD were randomized to sertraline or placebo. Eight subjects from the sertraline arm and five from the placebo arm discontinued from the study. Furthermore, four subjects did not have a successful blood draw. Hence, genotypes for 41 subjects (20 on placebo and 21 on sertraline) were determined for several genes involved in the serotonin pathway including the serotonin transporter-linked polymorphic region (5-HTTLPR), the tryptophan hydroxylase 2 (TPH2), and the Brain-Derived Neurotrophic Factor (BDNF). In addition, plasma levels of BDNF, Matrix metallopeptidase 9 (MMP-9) and a selected panel of cytokines were determined at baseline and post-treatment. Intent-to-treat analysis revealed several primary significant correlations between molecular changes and the Mullen Scales of Early Learning (MSEL) and Clinical Global Impression Scale - Improvement (CGI-I) of treatment and control groups but they were not significant after adjustment for multiple testing. Thus, sertraline showed no benefit for treatment of young children with ASD in language development or changes in molecular markers in this study. These results indicate that sertraline may not be beneficial for the treatment of children with ASD; however, further investigation of larger groups as well as longer term follow-up studies are warranted.

Dataset Information

Erythrocyte fatty acid profiles in children are not predictive of autism spectrum disorder status: a case control study.

Publications

Erythrocyte fatty acid profiles in children are not predictive of autism spectrum disorder status: a case control study.

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