Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder / Andrew W. ZIMMERMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 44 p. Titre : Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. JILL JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur Article en page(s) : 44 p. Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00451-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. JILL JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur . - 44 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 44 p. Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1186/s13229-021-00451-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli / Stephen BENT in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 35p. Titre : Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli Type de document : Texte imprimé et/ou numérique Auteurs : Stephen BENT, Auteur ; B. LAWTON, Auteur ; T. WARREN, Auteur ; F. WIDJAJA, Auteur ; K. DANG, Auteur ; J. W. FAHEY, Auteur ; Brian CORNBLATT, Auteur ; J. M. KINCHEN, Auteur ; K. DELUCCHI, Auteur ; R. L. HENDREN, Auteur Article en page(s) : 35p. Langues : Anglais (eng) Mots-clés : Adolescent  Antioxidants/administration & dosage/analysis/therapeutic use  Autistic Disorder/drug therapy/urine  Biomarkers/urine  Brassica/chemistry  Child  Female  Humans  Isothiocyanates/administration & dosage/analysis/therapeutic use  Male  Metabolome  Social Behavior  Young Adult  Antioxidant  Autism  Biomarker  Metabolomics Index. décimale : PER Périodiques Résumé : Background: Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds, was recently shown to lead to improvements in behavior and social responsiveness in children with ASD. We conducted the current open-label study to determine if we could identify changes in urinary metabolites that were associated with clinical improvements with the goal of identifying a potential mechanism of action. Methods: Children and young adults enrolled in a school for children with ASD and related neurodevelopmental disorders were recruited to participate in a 12-week, open-label study of sulforaphane. Fasting urinary metabolites and measures of behavior (Aberrant Behavior Checklist-ABC) and social responsiveness (Social Responsiveness Scale-SRS) were measured at baseline and at the end of the study. Pearson's correlation coefficient was calculated for the pre- to post-intervention change in each of the two clinical scales (ABS and SRS) versus the change in each metabolite. Results: Fifteen children completed the 12-week study. Mean scores on both symptom measures showed improvements (decreases) over the study period, but only the change in the SRS was significant. The ABC improved - 7.1 points (95% CI - 17.4 to 3.2), and the SRS improved - 9.7 points (95% CI - 18.7 to - 0.8). We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism. Conclusions: Urinary metabolomics analysis is a useful tool to identify pathways that may be involved in the mechanism of action of treatments targeting abnormal physiology in ASD. Trial registration: This study was prospectively registered at clinicaltrials.gov (NCT02654743) on January 11, 2016. En ligne : https://dx.doi.org/10.1186/s13229-018-0218-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli [Texte imprimé et/ou numérique] / Stephen BENT, Auteur ; B. LAWTON, Auteur ; T. WARREN, Auteur ; F. WIDJAJA, Auteur ; K. DANG, Auteur ; J. W. FAHEY, Auteur ; Brian CORNBLATT, Auteur ; J. M. KINCHEN, Auteur ; K. DELUCCHI, Auteur ; R. L. HENDREN, Auteur . - 35p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 35p. Mots-clés : Adolescent  Antioxidants/administration & dosage/analysis/therapeutic use  Autistic Disorder/drug therapy/urine  Biomarkers/urine  Brassica/chemistry  Child  Female  Humans  Isothiocyanates/administration & dosage/analysis/therapeutic use  Male  Metabolome  Social Behavior  Young Adult  Antioxidant  Autism  Biomarker  Metabolomics Index. décimale : PER Périodiques Résumé : Background: Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds, was recently shown to lead to improvements in behavior and social responsiveness in children with ASD. We conducted the current open-label study to determine if we could identify changes in urinary metabolites that were associated with clinical improvements with the goal of identifying a potential mechanism of action. Methods: Children and young adults enrolled in a school for children with ASD and related neurodevelopmental disorders were recruited to participate in a 12-week, open-label study of sulforaphane. Fasting urinary metabolites and measures of behavior (Aberrant Behavior Checklist-ABC) and social responsiveness (Social Responsiveness Scale-SRS) were measured at baseline and at the end of the study. Pearson's correlation coefficient was calculated for the pre- to post-intervention change in each of the two clinical scales (ABS and SRS) versus the change in each metabolite. Results: Fifteen children completed the 12-week study. Mean scores on both symptom measures showed improvements (decreases) over the study period, but only the change in the SRS was significant. The ABC improved - 7.1 points (95% CI - 17.4 to 3.2), and the SRS improved - 9.7 points (95% CI - 18.7 to - 0.8). We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism. Conclusions: Urinary metabolomics analysis is a useful tool to identify pathways that may be involved in the mechanism of action of treatments targeting abnormal physiology in ASD. Trial registration: This study was prospectively registered at clinicaltrials.gov (NCT02654743) on January 11, 2016. En ligne : https://dx.doi.org/10.1186/s13229-018-0218-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Maternal Obesity/Diabetes, Plasma Branched-Chain Amino Acids, and Autism Spectrum Disorder Risk in Urban Low-Income Children: Evidence of Sex Difference / Anita A PANJWANI in Autism Research, 12-10 (October 2019)  

Public ISBD [article]  inAutism Research > 12-10 (October 2019) . - p.1562-1573 Titre : Maternal Obesity/Diabetes, Plasma Branched-Chain Amino Acids, and Autism Spectrum Disorder Risk in Urban Low-Income Children: Evidence of Sex Difference Type de document : Texte imprimé et/ou numérique Auteurs : Anita A PANJWANI, Auteur ; Y. JI, Auteur ; J. W. FAHEY, Auteur ; A. PALMER, Auteur ; G. WANG, Auteur ; X. HONG, Auteur ; Barry S. ZUCKERMAN, Auteur ; X. WANG, Auteur Article en page(s) : p.1562-1573 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  branched-chain amino acids  diabetes mellitus  metabolomics  obesity  pre- and perinatal risk factors  sex differences Index. décimale : PER Périodiques Résumé : Maternal metabolic conditions are known risk factors for child autism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of child ASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72 hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019, 12: 1562-1573. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study investigated whether maternal obesity/diabetes and maternal circulating branched-chain amino acids (BCAAs) can jointly affect child ASD risk and whether the associations differ by child's sex. We found that the risk of ASD was greater among mothers with obesity/diabetes who also had elevated concentrations of BCAAs and that this risk was even greater for male children. These findings provide new evidence on fetal origins of ASD and sex difference and warrant additional investigation. En ligne : http://dx.doi.org/10.1002/aur.2177 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408 [article] Maternal Obesity/Diabetes, Plasma Branched-Chain Amino Acids, and Autism Spectrum Disorder Risk in Urban Low-Income Children: Evidence of Sex Difference [Texte imprimé et/ou numérique] / Anita A PANJWANI, Auteur ; Y. JI, Auteur ; J. W. FAHEY, Auteur ; A. PALMER, Auteur ; G. WANG, Auteur ; X. HONG, Auteur ; Barry S. ZUCKERMAN, Auteur ; X. WANG, Auteur . - p.1562-1573. Langues : Anglais (eng) in Autism Research > 12-10 (October 2019) . - p.1562-1573 Mots-clés : autism spectrum disorder  branched-chain amino acids  diabetes mellitus  metabolomics  obesity  pre- and perinatal risk factors  sex differences Index. décimale : PER Périodiques Résumé : Maternal metabolic conditions are known risk factors for child autism spectrum disorder (ASD). Branched-chain amino acids (BCAAs) are also associated with ASD. We examined the joint associations of maternal metabolic conditions and BCAAs on the risk of child ASD and whether the associations differed by child's sex. We analyzed 789 mother-infant pairs, a subset of the Boston Birth Cohort, from a predominantly urban, low-income, minority population. Maternal plasma BCAAs were measured by liquid chromatography-tandem mass spectrometry in samples collected 24-72 hr postpartum. A composite BCAA score was created using factor analysis, and prepregnancy obesity and diabetes (ob/DM) were combined into one variable. Logistic regression was used to explore the role of BCAAs as mediators or cofactors with ob/DM and child's sex on ASD risk. BCAA-ob/DM and BCAA-sex interactions were also examined. Maternal BCAAs alone were not associated with ASD and did not mediate the path between ob/DM and ASD. In the presence of maternal ob/DM, BCAA score was significantly associated with ASD (adjusted OR 2.33, 95% CI 1.18, 4.60). Interactions were present for valine with ob/DM and for valine and isoleucine with male sex on ASD risk. The odds ratio (OR) for risk of ASD was the greatest with all three risk factors combined-male sex, above median BCAA score, and ob/DM (OR 10.79, 95% CI 4.40, 26.42). Similar patterns were found for other developmental disorders, though not as strong as for ASD. Additional studies are warranted to clarify the role of maternal BCAAs, ob/DM, and child's sex in ASD. Autism Res 2019, 12: 1562-1573. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study investigated whether maternal obesity/diabetes and maternal circulating branched-chain amino acids (BCAAs) can jointly affect child ASD risk and whether the associations differ by child's sex. We found that the risk of ASD was greater among mothers with obesity/diabetes who also had elevated concentrations of BCAAs and that this risk was even greater for male children. These findings provide new evidence on fetal origins of ASD and sex difference and warrant additional investigation. En ligne : http://dx.doi.org/10.1002/aur.2177 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=408

Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder / Andrew W. ZIMMERMAN in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 38 p. Titre : Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. J. JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur Article en page(s) : 38 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Biomarkers  Clinical trial  Placebo effects  Sulforaphane  defendants in matters related to pediatric neurology and Autism Spectrum Disorder.  JWF retired from the full-time faculty at Johns Hopkins in mid-2020, and now serves  as a scientific advisor to Brassica Protection Products LLC (Baltimore, MD, USA),  which produces a glucoraphanin-rich broccoli seed extract that it supplies to the  supplement industry. AWZ is named on a patent on the use of sulforaphane for the  treatment of autism that has been assigned to Johns Hopkins University. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI -?0.46, 0.88 and 0.10; 95% CI -?0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d -?0.96; 95% CI -?1.73, -?0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00447-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Andrew W. ZIMMERMAN, Auteur ; K. SINGH, Auteur ; S. L. CONNORS, Auteur ; H. LIU, Auteur ; Anita A PANJWANI, Auteur ; L. C. LEE, Auteur ; E. DIGGINS, Auteur ; A. FOLEY, Auteur ; S. MELNYK, Auteur ; I. N. SINGH, Auteur ; S. J. JAMES, Auteur ; R. E. FRYE, Auteur ; J. W. FAHEY, Auteur . - 38 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 38 p. Mots-clés : Autism spectrum disorder (ASD)  Biomarkers  Clinical trial  Placebo effects  Sulforaphane  defendants in matters related to pediatric neurology and Autism Spectrum Disorder.  JWF retired from the full-time faculty at Johns Hopkins in mid-2020, and now serves  as a scientific advisor to Brassica Protection Products LLC (Baltimore, MD, USA),  which produces a glucoraphanin-rich broccoli seed extract that it supplies to the  supplement industry. AWZ is named on a patent on the use of sulforaphane for the  treatment of autism that has been assigned to Johns Hopkins University. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sulforaphane (SF), an isothiocyanate in broccoli, has potential benefits relevant to autism spectrum disorder (ASD) through its effects on several metabolic and immunologic pathways. Previous clinical trials of oral SF demonstrated positive clinical effects on behavior in young men and changes in urinary metabolomics in children with ASD. METHODS: We conducted a 15-week randomized parallel double-blind placebo-controlled clinical trial with 15-week open-label treatment and 6-week no-treatment extensions in 57 children, ages 3-12 years, with ASD over 36 weeks. Twenty-eight were assigned SF and 29 received placebo (PL). Clinical effects, safety and tolerability of SF were measured as were biomarkers to elucidate mechanisms of action of SF in ASD. RESULTS: Data from 22 children taking SF and 23 on PL were analyzed. Treatment effects on the primary outcome measure, the Ohio Autism Clinical Impressions Scale (OACIS), in the general level of autism were not significant between SF and PL groups at 7 and 15 weeks. The effect sizes on the OACIS were non-statistically significant but positive, suggesting a possible trend toward greater improvement in those on treatment with SF (Cohen's d 0.21; 95% CI -?0.46, 0.88 and 0.10; 95% CI -?0.52, 0.72, respectively). Both groups improved in all subscales when on SF during the open-label phase. Caregiver ratings on secondary outcome measures improved significantly on the Aberrant Behavior Checklist (ABC) at 15 weeks (Cohen's d -?0.96; 95% CI -?1.73, -?0.15), but not on the Social Responsiveness Scale-2 (SRS-2). Ratings on the ABC and SRS-2 improved with a non-randomized analysis of the length of exposure to SF, compared to the pre-treatment baseline (p? En ligne : http://dx.doi.org/10.1186/s13229-021-00447-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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