The Neurobiology of Lipid Metabolism in Autism Spectrum Disorders

Abstract

Autism is a neurodevelopmental disorder characterized by impairments in communication and reciprocal social interaction, coupled with repetitive behavior, which typically manifests by 3 years of age. Multiple genes and early exposure to environmental factors are the etiological determinants of the disorder that contribute to variable expression of autism-related traits. Increasing evidence indicates that altered fatty acid metabolic pathways may affect proper function of the nervous system and contribute to autism spectrum disorders. This review provides an overview of the reported abnormalities associated with the synthesis of membrane fatty acids in individuals with autism as a result of insufficient dietary supplementation or genetic defects. Moreover, we discuss deficits associated with the release of arachidonic acid from the membrane phospholipids and its subsequent metabolism to bioactive prostaglandins via phospholipase A₂-cyclooxygenase biosynthetic pathway in autism spectrum disorders. The existing evidence for the involvement of lipid neurobiology in the pathology of neurodevelopmental disorders such as autism is compelling and opens up an interesting possibility for further investigation of this metabolic pathway.

Potential serum biomarkers from a metabolomics study of autism

“…25,55,56 Children with autism tend to have a lower level of polyunsaturated fatty acid, which contributes to maintenance of the structural and functional integrity of the central nervous system. [57][58][59][60][61][62][63][64][65][66][67] A double-blind randomized placebo-controlled study found that DHA or eicosapentaenoic acid added to ARA supplementation could reduce behavioural problems in children with autism. [68][69][70] This is consistent with our findings that DHA was significantly associated with CARS score, which measures the severity of autistic behaviours (Table 4).…”

Диференціальна Діагностика Макроцефалій (Мегаленцефалій) У дітей

“…Важливість простагландину E2 для забезпечення раннього нейрогенезу (11-15-та доба ембріонального роз-витку) підтверджується під час проведення експериментів на мишах [24]. В експериментах при нестачі ПГ E2 були виявлені порушення розвитку багатьох мозкових структур.…”

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

“…In an analysis of the FAs composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; and levels of AA and DHA were particularly decreased (p < 0.001) [325]. Reported abnormalities associated with the synthesis of lipid bilayer in ASD as a result of FAs insufficient dietary supplementation or genetic defects can contribute to the symptomatology of autism and individual variety (for review see [326]). A growing body of evidence suggests that individuals who have ASD may have low levels of these PUFAs, particularly DHA and the AA:DHA ratio.…”