Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a natur...

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Main Authors: Marco Colizzi, Riccardo Bortoletto, Rosalia Costa, Leonardo Zoccante
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/13/4/1346
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spelling doaj-61577df0b70f4b53a1523f11c8892fcd2021-04-18T23:00:23ZengMDPI AGNutrients2072-66432021-04-01131346134610.3390/nu13041346Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal EvidenceMarco Colizzi0Riccardo Bortoletto1Rosalia Costa2Leonardo Zoccante3Child and Adolescent Neuropsychiatry Unit, Maternal-Child Integrated Care Department, Integrated University Hospital of Verona, 37126 Verona, ItalyChild and Adolescent Neuropsychiatry Unit, Maternal-Child Integrated Care Department, Integrated University Hospital of Verona, 37126 Verona, ItalyCommunity Mental Health Team, Department of Mental Health, ASST Mantova, 46100 Mantua, ItalyChild and Adolescent Neuropsychiatry Unit, Maternal-Child Integrated Care Department, Integrated University Hospital of Verona, 37126 Verona, ItalyAutism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.https://www.mdpi.com/2072-6643/13/4/1346neurodevelopmentpervasive developmental disordercannabinoidsacylethanolaminesimmune responseglutamate
collection DOAJ
language English
format Article
sources DOAJ
author Marco Colizzi
Riccardo Bortoletto
Rosalia Costa
Leonardo Zoccante
spellingShingle Marco Colizzi
Riccardo Bortoletto
Rosalia Costa
Leonardo Zoccante
Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
Nutrients
neurodevelopment
pervasive developmental disorder
cannabinoids
acylethanolamines
immune response
glutamate
author_facet Marco Colizzi
Riccardo Bortoletto
Rosalia Costa
Leonardo Zoccante
author_sort Marco Colizzi
title Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
title_short Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
title_full Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
title_fullStr Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
title_full_unstemmed Palmitoylethanolamide and Its Biobehavioral Correlates in Autism Spectrum Disorder: A Systematic Review of Human and Animal Evidence
title_sort palmitoylethanolamide and its biobehavioral correlates in autism spectrum disorder: a systematic review of human and animal evidence
publisher MDPI AG
series Nutrients
issn 2072-6643
publishDate 2021-04-01
description Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.
topic neurodevelopment
pervasive developmental disorder
cannabinoids
acylethanolamines
immune response
glutamate
url https://www.mdpi.com/2072-6643/13/4/1346
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