Oxidative stress-related biomarkers in autism

Systematic review and meta-analyses

Alessandra Frustaci, Monica Neri, Alfredo Cesario, James Adams, Enrico Domenici, Bernardo Dalla Bernardina, Stefano Bonassi

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.

Original languageEnglish (US)
Pages (from-to)2128-2141
Number of pages14
JournalFree Radical Biology and Medicine
Volume52
Issue number10
DOIs
StatePublished - May 15 2012

Fingerprint

Oxidative stress
Biomarkers
Autistic Disorder
Meta-Analysis
Oxidative Stress
Blood
Association reactions
cysteinylglycine
Glutathione
Genes
Cystathionine
Methylenetetrahydrofolate Reductase (NADPH2)
Ceruloplasmin
Glutathione Disulfide
Thiobarbituric Acid Reactive Substances
Homocysteine
Vitamin B 12
Glutathione Peroxidase
Polymorphism
Vitamin A

Keywords

  • Amino acids
  • Antioxidants
  • Autistic disorder
  • Biological markers
  • Case-control studies
  • Free radicals
  • Genetic polymorphisms
  • Glutathione
  • Oxidative stress
  • Oxidoreductases
  • Vitamins

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Frustaci, A., Neri, M., Cesario, A., Adams, J., Domenici, E., Dalla Bernardina, B., & Bonassi, S. (2012). Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses. Free Radical Biology and Medicine, 52(10), 2128-2141. https://doi.org/10.1016/j.freeradbiomed.2012.03.011

Oxidative stress-related biomarkers in autism : Systematic review and meta-analyses. / Frustaci, Alessandra; Neri, Monica; Cesario, Alfredo; Adams, James; Domenici, Enrico; Dalla Bernardina, Bernardo; Bonassi, Stefano.

In: Free Radical Biology and Medicine, Vol. 52, No. 10, 15.05.2012, p. 2128-2141.

Research output: Contribution to journalArticle

Frustaci, A, Neri, M, Cesario, A, Adams, J, Domenici, E, Dalla Bernardina, B & Bonassi, S 2012, 'Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses', Free Radical Biology and Medicine, vol. 52, no. 10, pp. 2128-2141. https://doi.org/10.1016/j.freeradbiomed.2012.03.011
Frustaci, Alessandra ; Neri, Monica ; Cesario, Alfredo ; Adams, James ; Domenici, Enrico ; Dalla Bernardina, Bernardo ; Bonassi, Stefano. / Oxidative stress-related biomarkers in autism : Systematic review and meta-analyses. In: Free Radical Biology and Medicine. 2012 ; Vol. 52, No. 10. pp. 2128-2141.
@article{35f2376e8c674e0f99dde7608463065a,
title = "Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses",
abstract = "Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27{\%}), glutathione peroxidase (18{\%}), methionine (13{\%}), and cysteine (14{\%}) and increased concentrations of oxidized glutathione (45{\%}) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95{\%} CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.",
keywords = "Amino acids, Antioxidants, Autistic disorder, Biological markers, Case-control studies, Free radicals, Genetic polymorphisms, Glutathione, Oxidative stress, Oxidoreductases, Vitamins",
author = "Alessandra Frustaci and Monica Neri and Alfredo Cesario and James Adams and Enrico Domenici and {Dalla Bernardina}, Bernardo and Stefano Bonassi",
year = "2012",
month = "5",
day = "15",
doi = "10.1016/j.freeradbiomed.2012.03.011",
language = "English (US)",
volume = "52",
pages = "2128--2141",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - Oxidative stress-related biomarkers in autism

T2 - Systematic review and meta-analyses

AU - Frustaci, Alessandra

AU - Neri, Monica

AU - Cesario, Alfredo

AU - Adams, James

AU - Domenici, Enrico

AU - Dalla Bernardina, Bernardo

AU - Bonassi, Stefano

PY - 2012/5/15

Y1 - 2012/5/15

N2 - Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.

AB - Autism spectrum disorders (ASDs) are rarely diagnosed in children younger than 2 years, because diagnosis is based entirely on behavioral tests. Oxidative damage may play a central role in this pathogenesis, together with the interconnected transmethylation cycle and transsulfuration pathway. In an attempt to clarify and quantify the relationship between oxidative stress-related blood biomarkers and ASDs, a systematic literature review was carried out. For each identified study, mean biomarker levels were compared in cases and controls providing a point estimate, the mean ratio, for each biomarker. After meta-analysis, the ASD patients showed decreased blood levels of reduced glutathione (27%), glutathione peroxidase (18%), methionine (13%), and cysteine (14%) and increased concentrations of oxidized glutathione (45%) relative to controls, whereas superoxide dismutase, homocysteine, and cystathionine showed no association with ASDs. For the C677T allele in the methylene tetrahydrofolate reductase gene (MTHFR), homozygous mutant subjects (TT) showed a meta-OR of 2.26 (95% CI 1.30-3.91) of being affected by ASD with respect to the homozygous nonmutant (CC). Case-control studies on blood levels of vitamins suggest a lack of association (folic acid and vitamin B12) or rare association (vitamins A, B6, C, D, E). Sparse results were available for other biomarkers (ceruloplasmin, catalase, cysteinylglycine, thiobarbituric acid-reactive substances, nitric oxide) and for polymorphisms in other genes. Existing evidence is heterogeneous and many studies are limited by small sample size and effects. In conclusion, existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.

KW - Amino acids

KW - Antioxidants

KW - Autistic disorder

KW - Biological markers

KW - Case-control studies

KW - Free radicals

KW - Genetic polymorphisms

KW - Glutathione

KW - Oxidative stress

KW - Oxidoreductases

KW - Vitamins

UR - http://www.scopus.com/inward/record.url?scp=84861035734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861035734&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2012.03.011

DO - 10.1016/j.freeradbiomed.2012.03.011

M3 - Article

VL - 52

SP - 2128

EP - 2141

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 10

ER -