Diffusional kurtosis imaging of the corpus callosum in autism / Y. V. SUI in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 62 p. Titre : Diffusional kurtosis imaging of the corpus callosum in autism Type de document : Texte imprimé et/ou numérique Auteurs : Y. V. SUI, Auteur ; J. DONALDSON, Auteur ; L. MILES, Auteur ; James S. BABB, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; M. LAZAR, Auteur Article en page(s) : 62 p. Langues : Anglais (eng) Mots-clés : Adolescent  Adult  Autistic Disorder/*diagnostic imaging/physiopathology  Case-Control Studies  Corpus Callosum/*diagnostic imaging  Humans  Magnetic Resonance Imaging  Wechsler Scales  White Matter/diagnostic imaging  *Autism  *Corpus callosum  *Diffusional kurtosis imaging  *Interhemispheric connectivity  *Processing speed  Medicine. All participants provided informed consent at the time of their  visit.The authors give consent for this manuscript to be published.The authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined. Methods: We employed diffusional kurtosis imaging (DKI) metrics to characterize white matter properties within five discrete segments of the corpus callosum in 17 typically developing (TD) adults and 16 age-matched participants with ASD without co-occurring intellectual disability (ID). The DKI metrics included axonal water fraction (f axon) and intra-axonal diffusivity (D axon), which reflect axonal density and caliber, and extra-axonal radial (RDextra) and axial (ADextra) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined. Results: ASD group had significantly decreased callosal f axon and D axon (p = .01 and p = .045), particularly in the midbody, isthmus, and splenium. Regression analysis showed that variation in DKI metrics, primarily in the mid and posterior callosal regions explained up to 70.7% of the variance in processing speed scores for TD (p = .001) but not for ASD (p > .05). Conclusion: Decreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants. En ligne : https://dx.doi.org/10.1186/s13229-018-0245-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Diffusional kurtosis imaging of the corpus callosum in autism [Texte imprimé et/ou numérique] / Y. V. SUI, Auteur ; J. DONALDSON, Auteur ; L. MILES, Auteur ; James S. BABB, Auteur ; Francisco Xavier CASTELLANOS, Auteur ; M. LAZAR, Auteur . - 62 p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 62 p. Mots-clés : Adolescent  Adult  Autistic Disorder/*diagnostic imaging/physiopathology  Case-Control Studies  Corpus Callosum/*diagnostic imaging  Humans  Magnetic Resonance Imaging  Wechsler Scales  White Matter/diagnostic imaging  *Autism  *Corpus callosum  *Diffusional kurtosis imaging  *Interhemispheric connectivity  *Processing speed  Medicine. All participants provided informed consent at the time of their  visit.The authors give consent for this manuscript to be published.The authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: The corpus callosum is implicated in the pathophysiology of autism spectrum disorder (ASD). However, specific structural deficits and underlying mechanisms are yet to be well defined. Methods: We employed diffusional kurtosis imaging (DKI) metrics to characterize white matter properties within five discrete segments of the corpus callosum in 17 typically developing (TD) adults and 16 age-matched participants with ASD without co-occurring intellectual disability (ID). The DKI metrics included axonal water fraction (f axon) and intra-axonal diffusivity (D axon), which reflect axonal density and caliber, and extra-axonal radial (RDextra) and axial (ADextra) diffusivities, which reflect myelination and microstructural organization of the extracellular space. The relationships between DKI metrics and processing speed, a cognitive feature known to be impaired in ASD, were also examined. Results: ASD group had significantly decreased callosal f axon and D axon (p = .01 and p = .045), particularly in the midbody, isthmus, and splenium. Regression analysis showed that variation in DKI metrics, primarily in the mid and posterior callosal regions explained up to 70.7% of the variance in processing speed scores for TD (p = .001) but not for ASD (p > .05). Conclusion: Decreased DKI metrics suggested that ASD may be associated with axonal deficits such as reduced axonal caliber and density in the corpus callosum, especially in the mid and posterior callosal areas. These data suggest that impaired interhemispheric connectivity may contribute to decreased processing speed in ASD participants. En ligne : https://dx.doi.org/10.1186/s13229-018-0245-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

The possible role of the kynurenine pathway in adolescent depression with melancholic features / Vilma GABBAY in Journal of Child Psychology and Psychiatry, 51-8 (August 2010)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 51-8 (August 2010) . - p.935-943 Titre : The possible role of the kynurenine pathway in adolescent depression with melancholic features Type de document : Texte imprimé et/ou numérique Auteurs : Vilma GABBAY, Auteur ; Rachel G. KLEIN, Auteur ; Yisrael KATZ, Auteur ; Sandra MENDOZA, Auteur ; Leah E. GUTTMAN, Auteur ; Carmen M. ALONSO, Auteur ; James S. BABB, Auteur ; Glenn S. HIRSCH, Auteur ; Leonard LIEBES, Auteur Année de publication : 2010 Article en page(s) : p.935-943 Langues : Anglais (eng) Mots-clés : Adolescent-depression indoleamine dioxygenase IDO kynurenine-(KYN) tryptophan(TRP) melancholic MDD subtypes Index. décimale : PER Périodiques Résumé : Background:  Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. Methods:  Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale-Revised (CDRS-R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons. Results:  As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R. Conclusions:  Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02245.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=108 [article] The possible role of the kynurenine pathway in adolescent depression with melancholic features [Texte imprimé et/ou numérique] / Vilma GABBAY, Auteur ; Rachel G. KLEIN, Auteur ; Yisrael KATZ, Auteur ; Sandra MENDOZA, Auteur ; Leah E. GUTTMAN, Auteur ; Carmen M. ALONSO, Auteur ; James S. BABB, Auteur ; Glenn S. HIRSCH, Auteur ; Leonard LIEBES, Auteur . - 2010 . - p.935-943. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 51-8 (August 2010) . - p.935-943 Mots-clés : Adolescent-depression indoleamine dioxygenase IDO kynurenine-(KYN) tryptophan(TRP) melancholic MDD subtypes Index. décimale : PER Périodiques Résumé : Background:  Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. Methods:  Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale-Revised (CDRS-R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons. Results:  As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R. Conclusions:  Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02245.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=108

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