Brain hyperserotonemia causes autism-relevant social deficits in mice / Miho TANAKA in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 60p. Titre : Brain hyperserotonemia causes autism-relevant social deficits in mice Type de document : texte imprimé Auteurs : Miho TANAKA, Auteur ; Atsushi SATO, Auteur ; Shinya KASAI, Auteur ; Yoko HAGINO, Auteur ; Hiroko KOTAJIMA-MURAKAMI, Auteur ; Hirofumi KASHII, Auteur ; Yukio TAKAMATSU, Auteur ; Yasumasa NISHITO, Auteur ; Masumi INAGAKI, Auteur ; Masashi MIZUGUCHI, Auteur ; F. Scott HALL, Auteur ; George R. UHL, Auteur ; Dennis MURPHY, Auteur ; Ichiro SORA, Auteur ; Kazutaka IKEDA, Auteur Article en page(s) : 60p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Heterozygous mice  Serotonin transporter  Tryptophan depletion Index. décimale : PER Périodiques Résumé : Background: Hyperserotonemia in the brain is suspected to be an endophenotype of autism spectrum disorder (ASD). Reducing serotonin levels in the brain through modulation of serotonin transporter function may improve ASD symptoms. Methods: We analyzed behavior and gene expression to unveil the causal mechanism of ASD-relevant social deficits using serotonin transporter (Sert) knockout mice. Results: Social deficits were observed in both heterozygous knockout mice (HZ) and homozygous knockout mice (KO), but increases in general anxiety were only observed in KO mice. Two weeks of dietary restriction of the serotonin precursor tryptophan ameliorated both brain hyperserotonemia and ASD-relevant social deficits in Sert HZ and KO mice. The expression of rather distinct sets of genes was altered in Sert HZ and KO mice, and a substantial portion of these genes was also affected by tryptophan depletion. Tryptophan depletion in Sert HZ and KO mice was associated with alterations in the expression of genes involved in signal transduction pathways initiated by changes in extracellular serotonin or melatonin, a derivative of serotonin. Only expression of the AU015836 gene was altered in both Sert HZ and KO mice. AU015836 expression and ASD-relevant social deficits normalized after dietary tryptophan restriction. Conclusions: These findings reveal a Sert gene dose-dependent effect on brain hyperserotonemia and related behavioral sequelae in ASD and a possible therapeutic target to normalize brain hyperserotonemia and ASD-relevant social deficits. En ligne : https://dx.doi.org/10.1186/s13229-018-0243-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Brain hyperserotonemia causes autism-relevant social deficits in mice [texte imprimé] / Miho TANAKA, Auteur ; Atsushi SATO, Auteur ; Shinya KASAI, Auteur ; Yoko HAGINO, Auteur ; Hiroko KOTAJIMA-MURAKAMI, Auteur ; Hirofumi KASHII, Auteur ; Yukio TAKAMATSU, Auteur ; Yasumasa NISHITO, Auteur ; Masumi INAGAKI, Auteur ; Masashi MIZUGUCHI, Auteur ; F. Scott HALL, Auteur ; George R. UHL, Auteur ; Dennis MURPHY, Auteur ; Ichiro SORA, Auteur ; Kazutaka IKEDA, Auteur . - 60p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 60p. Mots-clés : Autism spectrum disorder  Heterozygous mice  Serotonin transporter  Tryptophan depletion Index. décimale : PER Périodiques Résumé : Background: Hyperserotonemia in the brain is suspected to be an endophenotype of autism spectrum disorder (ASD). Reducing serotonin levels in the brain through modulation of serotonin transporter function may improve ASD symptoms. Methods: We analyzed behavior and gene expression to unveil the causal mechanism of ASD-relevant social deficits using serotonin transporter (Sert) knockout mice. Results: Social deficits were observed in both heterozygous knockout mice (HZ) and homozygous knockout mice (KO), but increases in general anxiety were only observed in KO mice. Two weeks of dietary restriction of the serotonin precursor tryptophan ameliorated both brain hyperserotonemia and ASD-relevant social deficits in Sert HZ and KO mice. The expression of rather distinct sets of genes was altered in Sert HZ and KO mice, and a substantial portion of these genes was also affected by tryptophan depletion. Tryptophan depletion in Sert HZ and KO mice was associated with alterations in the expression of genes involved in signal transduction pathways initiated by changes in extracellular serotonin or melatonin, a derivative of serotonin. Only expression of the AU015836 gene was altered in both Sert HZ and KO mice. AU015836 expression and ASD-relevant social deficits normalized after dietary tryptophan restriction. Conclusions: These findings reveal a Sert gene dose-dependent effect on brain hyperserotonemia and related behavioral sequelae in ASD and a possible therapeutic target to normalize brain hyperserotonemia and ASD-relevant social deficits. En ligne : https://dx.doi.org/10.1186/s13229-018-0243-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Polygenic and environmental influences on the course of African Americans' alcohol use from early adolescence through young adulthood / Jill A. RABINOWITZ in Development and Psychopathology, 32-2 (May 2020)  

Public ISBD [article]  inDevelopment and Psychopathology > 32-2 (May 2020) . - p.703-718 Titre : Polygenic and environmental influences on the course of African Americans' alcohol use from early adolescence through young adulthood Type de document : texte imprimé Auteurs : Jill A. RABINOWITZ, Auteur ; Rashelle J. MUSCI, Auteur ; Beth REBOUSSIN, Auteur ; Adam J. MILAM, Auteur ; Kelly S. BENKE, Auteur ; George R. UHL, Auteur ; Danielle Y. SISTO, Auteur ; Nicholas S. IALONGO, Auteur ; Brion MAHER, Auteur Article en page(s) : p.703-718 Langues : Anglais (eng) Mots-clés : alcohol use classes  antisocial behavior polygenic risk score  community disadvantage  internalizing symptoms polygenic risk score  parental monitoring Index. décimale : PER Périodiques Résumé : The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14-26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes. En ligne : http://dx.doi.org/10.1017/s0954579419000701 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=426 [article] Polygenic and environmental influences on the course of African Americans' alcohol use from early adolescence through young adulthood [texte imprimé] / Jill A. RABINOWITZ, Auteur ; Rashelle J. MUSCI, Auteur ; Beth REBOUSSIN, Auteur ; Adam J. MILAM, Auteur ; Kelly S. BENKE, Auteur ; George R. UHL, Auteur ; Danielle Y. SISTO, Auteur ; Nicholas S. IALONGO, Auteur ; Brion MAHER, Auteur . - p.703-718. Langues : Anglais (eng) in Development and Psychopathology > 32-2 (May 2020) . - p.703-718 Mots-clés : alcohol use classes  antisocial behavior polygenic risk score  community disadvantage  internalizing symptoms polygenic risk score  parental monitoring Index. décimale : PER Périodiques Résumé : The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14-26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes. En ligne : http://dx.doi.org/10.1017/s0954579419000701 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=426

Polygenic Score × Intervention Moderation: An application of discrete-time survival analysis to modeling the timing of first tobacco use among urban youth / Rashelle J. MUSCI in Development and Psychopathology, 27-1 (February 2015)  

Public ISBD [article]  inDevelopment and Psychopathology > 27-1 (February 2015) . - p.111-122 Titre : Polygenic Score × Intervention Moderation: An application of discrete-time survival analysis to modeling the timing of first tobacco use among urban youth Type de document : texte imprimé Auteurs : Rashelle J. MUSCI, Auteur ; Katherine E. MASYN, Auteur ; George UHL, Auteur ; Brion MAHER, Auteur ; Sheppard G. KELLAM, Auteur ; Nicholas S. IALONGO, Auteur Article en page(s) : p.111-122 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial. The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation and tobacco use (Uhl et al., 2014). Using data from a longitudinal preventive intervention study, we examined age of first tobacco use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found a main effect of the intervention, with the intervention participants reporting their first cigarette smoked at an age significantly later than controls. We also found an Intervention × Polygenic Score interaction, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use. These results are consistent with Belsky and colleagues' (e.g., Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Belsky & Pleuss, 2009, 2013; Ellis, Boyce, Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2011) differential susceptibility hypothesis and the concept of “for better or worse,” wherein the expression of genetic variants are optimally realized in the context of an enriched environment, such as provided by a preventive intervention. En ligne : http://dx.doi.org/10.1017/S0954579414001333 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=257 [article] Polygenic Score × Intervention Moderation: An application of discrete-time survival analysis to modeling the timing of first tobacco use among urban youth [texte imprimé] / Rashelle J. MUSCI, Auteur ; Katherine E. MASYN, Auteur ; George UHL, Auteur ; Brion MAHER, Auteur ; Sheppard G. KELLAM, Auteur ; Nicholas S. IALONGO, Auteur . - p.111-122. Langues : Anglais (eng) in Development and Psychopathology > 27-1 (February 2015) . - p.111-122 Index. décimale : PER Périodiques Résumé : The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial. The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation and tobacco use (Uhl et al., 2014). Using data from a longitudinal preventive intervention study, we examined age of first tobacco use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found a main effect of the intervention, with the intervention participants reporting their first cigarette smoked at an age significantly later than controls. We also found an Intervention × Polygenic Score interaction, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use. These results are consistent with Belsky and colleagues' (e.g., Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Belsky & Pleuss, 2009, 2013; Ellis, Boyce, Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2011) differential susceptibility hypothesis and the concept of “for better or worse,” wherein the expression of genetic variants are optimally realized in the context of an enriched environment, such as provided by a preventive intervention. En ligne : http://dx.doi.org/10.1017/S0954579414001333 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=257

The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence / Rashelle J. MUSCI in Development and Psychopathology, 28-1 (February 2016)  

Public ISBD [article]  inDevelopment and Psychopathology > 28-1 (February 2016) . - p.225-237 Titre : The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence Type de document : texte imprimé Auteurs : Rashelle J. MUSCI, Auteur ; Katherine E. MASYN, Auteur ; Kelly S. BENKE, Auteur ; Brion MAHER, Auteur ; George UHL, Auteur ; Nicholas S. IALONGO, Auteur Article en page(s) : p.225-237 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Internalizing symptoms during adolescence and beyond is a major public health concern, particularly because severe symptoms can lead to the diagnosis of a number of serious psychiatric conditions. This study utilizes a unique sample with a complex statistical method in order to explore Gene × Environment interactions found in internalizing symptoms during adolescence. Data for this study were drawn from a longitudinal prevention intervention study (n = 798) of Baltimore city school children. Internalizing symptom data were collected using self-report and blood or saliva samples genotyped using Affymetrix 6.0 microarrays. A major depression polygenic score was created for each individual using information from the major depressive disorder Psychiatric Genetics Consortium and used as a predictor in a latent trait–state–occasion model. The major depressive disorder polygenic score was a significant predictor of the stable latent trait variable, which captures time-independent phenotypic variability. In addition, an early childhood stressor of death or divorce was a significant predictor of occasion-specific variables. A Gene × Environment interaction was not a significant predictor of the latent trait or occasion variables. These findings support the importance of genetics on the stable latent trait portion of internalizing symptoms across adolescence. En ligne : http://dx.doi.org/10.1017/S0954579415000401 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=278 [article] The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence [texte imprimé] / Rashelle J. MUSCI, Auteur ; Katherine E. MASYN, Auteur ; Kelly S. BENKE, Auteur ; Brion MAHER, Auteur ; George UHL, Auteur ; Nicholas S. IALONGO, Auteur . - p.225-237. Langues : Anglais (eng) in Development and Psychopathology > 28-1 (February 2016) . - p.225-237 Index. décimale : PER Périodiques Résumé : Internalizing symptoms during adolescence and beyond is a major public health concern, particularly because severe symptoms can lead to the diagnosis of a number of serious psychiatric conditions. This study utilizes a unique sample with a complex statistical method in order to explore Gene × Environment interactions found in internalizing symptoms during adolescence. Data for this study were drawn from a longitudinal prevention intervention study (n = 798) of Baltimore city school children. Internalizing symptom data were collected using self-report and blood or saliva samples genotyped using Affymetrix 6.0 microarrays. A major depression polygenic score was created for each individual using information from the major depressive disorder Psychiatric Genetics Consortium and used as a predictor in a latent trait–state–occasion model. The major depressive disorder polygenic score was a significant predictor of the stable latent trait variable, which captures time-independent phenotypic variability. In addition, an early childhood stressor of death or divorce was a significant predictor of occasion-specific variables. A Gene × Environment interaction was not a significant predictor of the latent trait or occasion variables. These findings support the importance of genetics on the stable latent trait portion of internalizing symptoms across adolescence. En ligne : http://dx.doi.org/10.1017/S0954579415000401 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=278

---

1 (1 - 4 / 4) Par page : 25 50 100 200