Autism Spectrum Disorder (ASD) is a complex and multifactorial condition that affects neurological development and manifests itself through challenges in social communication and repetitive behaviors. The etiology of ASD remains an enigma, but growing evidence suggests a strong association with dysregulations in lipid metabolism and inflammatory processes.
A recent study from the Hamamatsu Birth Cohort for Mothers and Children (HBC) in Japan investigated the relationship between metabolites of polyunsaturated fatty acids (PUFAs) in umbilical cord blood and ASD symptoms in children at 6 years of age. The results revealed a significant association between elevated levels of dihydroxyeicosatrienoates (diHETrEs), derived from arachidonic acid (AA), and the severity of ASD symptoms, particularly in girls. The study also identified a correlation between higher levels of 11,12-diHETrE and difficulties in social adaptation, suggesting a crucial role for these metabolites in the developmental trajectory of children with ASD.
These findings support the hypothesis that maternal immune activation and fetal neuroinflammation play an important role in the pathogenesis of ASD. diHETrE, a metabolite with pro-inflammatory properties, may act as a key mediator in this process, affecting the development of the central nervous system and contributing to the emergence of ASD symptoms.
Although more research is needed to elucidate the precise mechanisms involved, the HBC Cohort study opens new perspectives for understanding the etiology of ASD and developing preventive and therapeutic strategies. Identification of early biomarkers, such as diHETrE, may enable early intervention and personalized monitoring of at-risk children, potentially improving their developmental outcomes and quality of life.
What is dihydroxyeicosatrienoates (diHETrEs) and what does it do?
Dihydroxyeicosatrienoates (diHETrEs) are metabolites of arachidonic acid (AA), an omega-6 fatty acid present in cell membranes. AA is converted to epoxyeicosatrienoates (EETs) by cytochrome P450 enzymes and subsequently to diHETrEs by the soluble enzyme epoxide hydrolase (sEH).
Functions of diHETrEs:
– Inflammatory mediators: The article highlights that diHETrEs, despite having low biological activity compared to their precursors, EETs, have pro-inflammatory properties. This inflammatory feature may be crucial in the observed association between elevated diHETrEs levels and ASD symptoms, possibly through maternal immune activation and fetal neuroinflammation.
– Other functions: The text mentions that 11,12-diHETrE, a specific type of diHETrE, has a potent vasodilatory effect and that 14,15-diHETrE is involved in lipid metabolism and inflammatory signaling. However, fully understanding the biological functions of diHETrEs still requires further investigation.
In summary, diHETrEs are arachidonic acid metabolites with pro-inflammatory properties that may play an important role in the development of ASD, possibly through modulation of the immune response and neuroinflammation.
References:
Hirai T, Umeda N, Harada T, et al. Arachidonic acid-derived dihydroxy fatty acids in neonatal cord blood report symptoms of autism spectrum disorders and social adaptive functioning: Hamamatsu Birth Cohort for Mothers and Children (HBC Study). Psychiatry Clin Neurosci. 2024;00:1–9. https://doi.org/10.1111/pcn.13710
