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Auteur John P. CAPITANIO |
Documents disponibles écrits par cet auteur (5)
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Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality / A. K. MYERS in Autism Research, 14-7 (July 2021)
[article]
Titre : Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality Type de document : Texte imprimé et/ou numérique Auteurs : A. K. MYERS, Auteur ; Catherine F. TALBOT, Auteur ; L. A. DEL ROSSO, Auteur ; A. C. MANESS, Auteur ; S. M. V. SIMMONS, Auteur ; J. P. GARNER, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : p.1332-1346 Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/epidemiology Autistic Disorder Humans Macaca mulatta Morbidity Social Behavior Social Responsiveness Scale animal model autism spectrum disorder medical morbidities rhesus macaque social behavior Index. décimale : PER Périodiques Résumé : People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model. En ligne : http://dx.doi.org/10.1002/aur.2512 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449
in Autism Research > 14-7 (July 2021) . - p.1332-1346[article] Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality [Texte imprimé et/ou numérique] / A. K. MYERS, Auteur ; Catherine F. TALBOT, Auteur ; L. A. DEL ROSSO, Auteur ; A. C. MANESS, Auteur ; S. M. V. SIMMONS, Auteur ; J. P. GARNER, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - p.1332-1346.
Langues : Anglais (eng)
in Autism Research > 14-7 (July 2021) . - p.1332-1346
Mots-clés : Animals Autism Spectrum Disorder/epidemiology Autistic Disorder Humans Macaca mulatta Morbidity Social Behavior Social Responsiveness Scale animal model autism spectrum disorder medical morbidities rhesus macaque social behavior Index. décimale : PER Périodiques Résumé : People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model. En ligne : http://dx.doi.org/10.1002/aur.2512 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=449 Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / O. OZTAN in Molecular Autism, 12 (2021)
[article]
Titre : Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys Type de document : Texte imprimé et/ou numérique Auteurs : O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : Arginine vasopressin Autism spectrum disorder Biomarker Cerebrospinal fluid Kinase signaling pathway Oxytocin Rhesus macaque Social responsiveness scale Social trait variation the University of California, San Francisco (UCSF) have filed patent applications related to biological measures studied herein (Stanford University: PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism spectrum disorder” UCSF: PCT/US2016/014623 “Methods of diagnosing and treating autism spectrum disorders”). These patents have not been granted or licensed, and no study author is receiving any financial compensation at this time. EHS serves on the advisory board for Retrophin Inc. All other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N?=?76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n?=?43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n?=?57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n?=?75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 50 p.[article] Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys [Texte imprimé et/ou numérique] / O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 50 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 50 p.
Mots-clés : Arginine vasopressin Autism spectrum disorder Biomarker Cerebrospinal fluid Kinase signaling pathway Oxytocin Rhesus macaque Social responsiveness scale Social trait variation the University of California, San Francisco (UCSF) have filed patent applications related to biological measures studied herein (Stanford University: PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism spectrum disorder” UCSF: PCT/US2016/014623 “Methods of diagnosing and treating autism spectrum disorders”). These patents have not been granted or licensed, and no study author is receiving any financial compensation at this time. EHS serves on the advisory board for Retrophin Inc. All other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N?=?76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n?=?43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n?=?57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n?=?75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population / Catherine F. TALBOT in Autism Research, 13-9 (September 2020)
[article]
Titre : A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population Type de document : Texte imprimé et/ou numérique Auteurs : Catherine F. TALBOT, Auteur ; Joseph P. GARNER, Auteur ; Alyssa C. MANESS, Auteur ; Brenda MCCOWAN, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : p.1465-1475 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Naturally low-social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (ASD). To more efficiently identify low-social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque Social Responsiveness Scale (mSRS), an instrument previously derived from the human ASD screening tool. We performed quantitative social behavior assessments and mSRS ratings on a total of N = 349 rhesus macaques (Macaca mulatta) housed in large, outdoor corrals. In one cohort (N = 116), we conducted inter-rater and test-retest reliabilities, and in a second cohort (N = 233), we evaluated the convergent construct and predictive validity of the mSRS-Revised (mSRS-R). Only 17 of the original 36 items demonstrated inter-rater and test–retest reliability, resulting in the 17-item mSRS-R. The mSRS-R showed strong validity: mSRS-R scores robustly predicted monkeys' social behavior frequencies in home corrals. Monkeys that scored 1.5 standard deviations from the mean on nonsocial behavior likewise exhibited significantly more autistic-like traits, and mSRS-R scores predicted individuals' social classification (low-social vs. high-social) with 96% accuracy (likelihood ratio chi-square = 25.07; P?0.0001). These findings indicate that the mSRS-R is a reliable, valid, and sensitive measure of social functioning, and like the human SRS, can be used as a high-throughput screening tool to identify socially impaired individuals in the general population. Lay Summary Variation in autistic traits can be measured in humans using the Social Responsiveness Scale (SRS). Here, we revised this scale for rhesus macaques (i.e., the mSRS-R), and showed that macaques exhibit individual differences in mSRS-R scores, and at the behavioral extremes, low-social vs. high-social monkeys exhibit more autistic-like traits. These results suggest that the mSRS-R can be used as a screening tool to rapidly and accurately identify low-social monkeys in the general population. Autism Res 2020, 13: 1465–1475. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2335 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431
in Autism Research > 13-9 (September 2020) . - p.1465-1475[article] A Psychometrically Robust Screening Tool To Rapidly Identify Socially Impaired Monkeys In The General Population [Texte imprimé et/ou numérique] / Catherine F. TALBOT, Auteur ; Joseph P. GARNER, Auteur ; Alyssa C. MANESS, Auteur ; Brenda MCCOWAN, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - p.1465-1475.
Langues : Anglais (eng)
in Autism Research > 13-9 (September 2020) . - p.1465-1475
Index. décimale : PER Périodiques Résumé : Naturally low-social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (ASD). To more efficiently identify low-social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque Social Responsiveness Scale (mSRS), an instrument previously derived from the human ASD screening tool. We performed quantitative social behavior assessments and mSRS ratings on a total of N = 349 rhesus macaques (Macaca mulatta) housed in large, outdoor corrals. In one cohort (N = 116), we conducted inter-rater and test-retest reliabilities, and in a second cohort (N = 233), we evaluated the convergent construct and predictive validity of the mSRS-Revised (mSRS-R). Only 17 of the original 36 items demonstrated inter-rater and test–retest reliability, resulting in the 17-item mSRS-R. The mSRS-R showed strong validity: mSRS-R scores robustly predicted monkeys' social behavior frequencies in home corrals. Monkeys that scored 1.5 standard deviations from the mean on nonsocial behavior likewise exhibited significantly more autistic-like traits, and mSRS-R scores predicted individuals' social classification (low-social vs. high-social) with 96% accuracy (likelihood ratio chi-square = 25.07; P?0.0001). These findings indicate that the mSRS-R is a reliable, valid, and sensitive measure of social functioning, and like the human SRS, can be used as a high-throughput screening tool to identify socially impaired individuals in the general population. Lay Summary Variation in autistic traits can be measured in humans using the Social Responsiveness Scale (SRS). Here, we revised this scale for rhesus macaques (i.e., the mSRS-R), and showed that macaques exhibit individual differences in mSRS-R scores, and at the behavioral extremes, low-social vs. high-social monkeys exhibit more autistic-like traits. These results suggest that the mSRS-R can be used as a screening tool to rapidly and accurately identify low-social monkeys in the general population. Autism Res 2020, 13: 1465–1475. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.2335 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431 Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism / Catherine F. TALBOT ; Laura A. DEL ROSSO ; Brenda MCCOWAN ; Sreetharan KANTHASWAMY ; David HAIG ; John P. CAPITANIO ; Karen J. PARKER in Molecular Autism, 14 (2023)
[article]
Titre : Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism Type de document : Texte imprimé et/ou numérique Auteurs : Catherine F. TALBOT, Auteur ; Laura A. DEL ROSSO, Auteur ; Brenda MCCOWAN, Auteur ; Sreetharan KANTHASWAMY, Auteur ; David HAIG, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 25 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N=407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (?(2)(P)) between sons that could uniquely be attributed to their shared genetics (?(2)(g)), expressed as ?(2)(g)/?(2)(P) (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h(2)). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. En ligne : http://dx.doi.org/10.1186/s13229-023-00556-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513
in Molecular Autism > 14 (2023) . - 25 p.[article] Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism [Texte imprimé et/ou numérique] / Catherine F. TALBOT, Auteur ; Laura A. DEL ROSSO, Auteur ; Brenda MCCOWAN, Auteur ; Sreetharan KANTHASWAMY, Auteur ; David HAIG, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 25 p.
Langues : Anglais (eng)
in Molecular Autism > 14 (2023) . - 25 p.
Index. décimale : PER Périodiques Résumé : BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N=407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (?(2)(P)) between sons that could uniquely be attributed to their shared genetics (?(2)(g)), expressed as ?(2)(g)/?(2)(P) (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h(2)). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. En ligne : http://dx.doi.org/10.1186/s13229-023-00556-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 Serotonin pathway gene–gene and gene–environment interactions influence behavioral stress response in infant rhesus macaques / Erin L. KINNALLY in Development and Psychopathology, 22-1 (January 2010)
[article]
Titre : Serotonin pathway gene–gene and gene–environment interactions influence behavioral stress response in infant rhesus macaques Type de document : Texte imprimé et/ou numérique Auteurs : Erin L. KINNALLY, Auteur ; Sally MENDOZA, Auteur ; Genesio M. KARERE, Auteur ; Leslie A. LYONS, Auteur ; William A. MASON, Auteur ; John P. CAPITANIO, Auteur Année de publication : 2010 Article en page(s) : p.35-44 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : A subset of serotonin (5-HT) pathway polymorphisms has been shown to confer risk for psychological dysfunction, particularly in individuals who experience early adversity. Understanding the developmental processes underlying these Gene × Environment interactions will strengthen the search for risk factors for behavioral dysfunction. We investigated the combined influence of two serotonin pathway polymorphisms and species-atypical, and possibly adverse, rearing (nursery rearing [NR]) on two dimensions of behavioral stress response in infant rhesus macaques. We hypothesized that the experience of NR and possession of both “high-risk” genotypes (genotypes that are thought to confer low 5-HT function) would predict the greatest behavioral stress response to maternal/social separation. Using a matched-pair design, the impact of early experience and the serotonin transporter (rh5-HTTLPR) and monoamine oxidase A (rhMAO-A-LPR) promoter polymorphisms on behavioral reactivity of 136 infant rhesus macaques (90–120 days of age) during a 25-hr social separation/relocation procedure was assessed. Each pair included one infant reared with mother in a large, outdoor field enclosure (field rearing) and one infant reared in a nursery (NR). Pairs were matched for putative gene activity of each polymorphism, sex, age, and weight at testing. Behavioral responses in a “human intruder” test were recorded, and activity and emotional reactivity composites were created to detect different aspects of psychological adaptation to stress. Our hypothesis that high-risk groups would be the most reactive to stress was not entirely borne out. Rh5-HTTLPR × rhMAOA-LPR interactions predicted emotional reactivity and tended to predict behavioral activity scores. Carriers of the two “low-risk” alleles exhibited the lowest behavioral activity, as might be predicted, but carriers of both “high-risk” alleles were two of four genotype groups exhibiting the highest observed Emotional Reactivity. Gene × Gene interactions were exacerbated by the experience of nursery rearing, as predicted, however. Finally, we suggest that genetic or environmental factors may mitigate the risk for behavioral dysregulation illustrated in the patterns of behavioral activity and emotional reactivity displayed by infants. En ligne : http://dx.doi.org/10.1017/s0954579409990241 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=969
in Development and Psychopathology > 22-1 (January 2010) . - p.35-44[article] Serotonin pathway gene–gene and gene–environment interactions influence behavioral stress response in infant rhesus macaques [Texte imprimé et/ou numérique] / Erin L. KINNALLY, Auteur ; Sally MENDOZA, Auteur ; Genesio M. KARERE, Auteur ; Leslie A. LYONS, Auteur ; William A. MASON, Auteur ; John P. CAPITANIO, Auteur . - 2010 . - p.35-44.
Langues : Anglais (eng)
in Development and Psychopathology > 22-1 (January 2010) . - p.35-44
Index. décimale : PER Périodiques Résumé : A subset of serotonin (5-HT) pathway polymorphisms has been shown to confer risk for psychological dysfunction, particularly in individuals who experience early adversity. Understanding the developmental processes underlying these Gene × Environment interactions will strengthen the search for risk factors for behavioral dysfunction. We investigated the combined influence of two serotonin pathway polymorphisms and species-atypical, and possibly adverse, rearing (nursery rearing [NR]) on two dimensions of behavioral stress response in infant rhesus macaques. We hypothesized that the experience of NR and possession of both “high-risk” genotypes (genotypes that are thought to confer low 5-HT function) would predict the greatest behavioral stress response to maternal/social separation. Using a matched-pair design, the impact of early experience and the serotonin transporter (rh5-HTTLPR) and monoamine oxidase A (rhMAO-A-LPR) promoter polymorphisms on behavioral reactivity of 136 infant rhesus macaques (90–120 days of age) during a 25-hr social separation/relocation procedure was assessed. Each pair included one infant reared with mother in a large, outdoor field enclosure (field rearing) and one infant reared in a nursery (NR). Pairs were matched for putative gene activity of each polymorphism, sex, age, and weight at testing. Behavioral responses in a “human intruder” test were recorded, and activity and emotional reactivity composites were created to detect different aspects of psychological adaptation to stress. Our hypothesis that high-risk groups would be the most reactive to stress was not entirely borne out. Rh5-HTTLPR × rhMAOA-LPR interactions predicted emotional reactivity and tended to predict behavioral activity scores. Carriers of the two “low-risk” alleles exhibited the lowest behavioral activity, as might be predicted, but carriers of both “high-risk” alleles were two of four genotype groups exhibiting the highest observed Emotional Reactivity. Gene × Gene interactions were exacerbated by the experience of nursery rearing, as predicted, however. Finally, we suggest that genetic or environmental factors may mitigate the risk for behavioral dysregulation illustrated in the patterns of behavioral activity and emotional reactivity displayed by infants. En ligne : http://dx.doi.org/10.1017/s0954579409990241 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=969