Lower circulating endocannabinoid levels in children with autism spectrum disorder
Abstract Background The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13229-019-0256-6 |
| _version_ | 1818910934214639616 |
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| author | Adi Aran Maya Eylon Moria Harel Lola Polianski Alina Nemirovski Sigal Tepper Aviad Schnapp Hanoch Cassuto Nadia Wattad Joseph Tam |
| author_facet | Adi Aran Maya Eylon Moria Harel Lola Polianski Alina Nemirovski Sigal Tepper Aviad Schnapp Hanoch Cassuto Nadia Wattad Joseph Tam |
| author_sort | Adi Aran |
| collection | DOAJ |
| description | Abstract Background The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6–21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5–21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results Children with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, P < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid “tone” in the brain, as found in animal models of ASD. |
| first_indexed | 2024-12-19T22:50:41Z |
| format | Article |
| id | doaj.art-d5fe0f1183d1429f9537e785e7a50de6 |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-12-19T22:50:41Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-d5fe0f1183d1429f9537e785e7a50de62022-12-21T20:02:50ZengBMCMolecular Autism2040-23922019-01-0110111110.1186/s13229-019-0256-6Lower circulating endocannabinoid levels in children with autism spectrum disorderAdi Aran0Maya Eylon1Moria Harel2Lola Polianski3Alina Nemirovski4Sigal Tepper5Aviad Schnapp6Hanoch Cassuto7Nadia Wattad8Joseph Tam9Neuropediatric Unit, Shaare Zedek Medical CenterObesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemNeuropediatric Unit, Shaare Zedek Medical CenterNeuropediatric Unit, Shaare Zedek Medical CenterObesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemDepartment of Nutritional Sciences, Tel Hai Academic CollegeNeuropediatric Unit, Shaare Zedek Medical CenterNeuropediatric Unit, Shaare Zedek Medical CenterNeuropediatric Unit, Shaare Zedek Medical CenterObesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemAbstract Background The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6–21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5–21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results Children with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, P < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid “tone” in the brain, as found in animal models of ASD.http://link.springer.com/article/10.1186/s13229-019-0256-6Autism spectrum disorderEndocannabinoid systemAnandamideN-arachidonoylethanolamine2-arachidonoylglycerolArachidonic acid |
| spellingShingle | Adi Aran Maya Eylon Moria Harel Lola Polianski Alina Nemirovski Sigal Tepper Aviad Schnapp Hanoch Cassuto Nadia Wattad Joseph Tam Lower circulating endocannabinoid levels in children with autism spectrum disorder Molecular Autism Autism spectrum disorder Endocannabinoid system Anandamide N-arachidonoylethanolamine 2-arachidonoylglycerol Arachidonic acid |
| title | Lower circulating endocannabinoid levels in children with autism spectrum disorder |
| title_full | Lower circulating endocannabinoid levels in children with autism spectrum disorder |
| title_fullStr | Lower circulating endocannabinoid levels in children with autism spectrum disorder |
| title_full_unstemmed | Lower circulating endocannabinoid levels in children with autism spectrum disorder |
| title_short | Lower circulating endocannabinoid levels in children with autism spectrum disorder |
| title_sort | lower circulating endocannabinoid levels in children with autism spectrum disorder |
| topic | Autism spectrum disorder Endocannabinoid system Anandamide N-arachidonoylethanolamine 2-arachidonoylglycerol Arachidonic acid |
| url | http://link.springer.com/article/10.1186/s13229-019-0256-6 |
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