Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm / Simona SPINELLI in Development and Psychopathology, 19-4 (Fall 2007)  

Public ISBD [article]  inDevelopment and Psychopathology > 19-4 (Fall 2007) . - p.977-987 Titre : Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm Type de document : Texte imprimé et/ou numérique Auteurs : Simona SPINELLI, Auteur ; Melanie L. SCHWANDT, Auteur ; Stephen G. LINDELL, Auteur ; Timothy K. NEWMAN, Auteur ; Markus HEILIG, Auteur ; Stephen J. SUOMI, Auteur ; J. Dee HIGLEY, Auteur ; David GOLDMAN, Auteur ; Christina S. BARR, Auteur Année de publication : 2007 Article en page(s) : p.977-987 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Human studies have suggested an association between a variable length polymorphism in the serotonin transporter gene promoter region and vulnerability to anxiety and depression. Relative to the long (l) allele, the short (s) allele increases the risk of developing depression in individuals exposed to stressful life events. An orthologue of the human variant is present in rhesus macaques and allows for studies in animals exposed to stress. Here, we used an established model of early life stress exposure, in which rhesus macaques are raised without adults in a group of peers (peer-only reared [PR]), or with their mothers. At 6 months of age, animals were subjected to 4-day long social separations for 4 consecutive weeks, with 3 days of reunion in between. Data were collected during both the acute (Day 1) and chronic phases (Days 2–4) of separation. Behavioral factors were separately extracted for each phase of separation. For acute separation, the behavioral factors generated were despair and behavioral pathology and, for the chronic phase despair, agitation, and behavioral pathology. During both phases of social separation, PR l/s animals were more likely to exhibit pathological behaviors, whereas PR l/l monkeys show higher levels of despair compared to the other three groups. These findings indicate that early stress affects the behavioral response to separation differently as a function of recombinant human serotonin transporter linked polymorphic repeat genotype and suggest that carriers of the s allele are not only more anxious but may also be more vulnerable to developing behavioral pathology in the face of chronic adversity. En ligne : http://dx.doi.org/10.1017/s095457940700048x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=181 [article] Association between the recombinant human serotonin transporter linked promoter region polymorphism and behavior in rhesus macaques during a separation paradigm [Texte imprimé et/ou numérique] / Simona SPINELLI, Auteur ; Melanie L. SCHWANDT, Auteur ; Stephen G. LINDELL, Auteur ; Timothy K. NEWMAN, Auteur ; Markus HEILIG, Auteur ; Stephen J. SUOMI, Auteur ; J. Dee HIGLEY, Auteur ; David GOLDMAN, Auteur ; Christina S. BARR, Auteur . - 2007 . - p.977-987. Langues : Anglais (eng) in Development and Psychopathology > 19-4 (Fall 2007) . - p.977-987 Index. décimale : PER Périodiques Résumé : Human studies have suggested an association between a variable length polymorphism in the serotonin transporter gene promoter region and vulnerability to anxiety and depression. Relative to the long (l) allele, the short (s) allele increases the risk of developing depression in individuals exposed to stressful life events. An orthologue of the human variant is present in rhesus macaques and allows for studies in animals exposed to stress. Here, we used an established model of early life stress exposure, in which rhesus macaques are raised without adults in a group of peers (peer-only reared [PR]), or with their mothers. At 6 months of age, animals were subjected to 4-day long social separations for 4 consecutive weeks, with 3 days of reunion in between. Data were collected during both the acute (Day 1) and chronic phases (Days 2–4) of separation. Behavioral factors were separately extracted for each phase of separation. For acute separation, the behavioral factors generated were despair and behavioral pathology and, for the chronic phase despair, agitation, and behavioral pathology. During both phases of social separation, PR l/s animals were more likely to exhibit pathological behaviors, whereas PR l/l monkeys show higher levels of despair compared to the other three groups. These findings indicate that early stress affects the behavioral response to separation differently as a function of recombinant human serotonin transporter linked polymorphic repeat genotype and suggest that carriers of the s allele are not only more anxious but may also be more vulnerable to developing behavioral pathology in the face of chronic adversity. En ligne : http://dx.doi.org/10.1017/s095457940700048x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=181

The serotonin transporter gene linked polymorphic region is associated with the behavioral response to repeated stress exposure in infant rhesus macaques / Simona SPINELLI in Development and Psychopathology, 24-1 (January 2012)  

Public ISBD [article]  inDevelopment and Psychopathology > 24-1 (January 2012) . - p.157-165 Titre : The serotonin transporter gene linked polymorphic region is associated with the behavioral response to repeated stress exposure in infant rhesus macaques Type de document : Texte imprimé et/ou numérique Auteurs : Simona SPINELLI, Auteur ; Melanie L. SCHWANDT, Auteur ; Stephen G. LINDELL, Auteur ; Markus HEILIG, Auteur ; Stephen J. SUOMI, Auteur ; J. Dee HIGLEY, Auteur ; David GOLDMAN, Auteur ; Christina S. BARR, Auteur Année de publication : 2012 Article en page(s) : p.157-165 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The short allele of the serotonin transporter linked polymorphic region (5-HTTLPR) moderates the effects of stress on vulnerability to mood and anxiety disorders. The mechanism by which this occurs may relate to differential sensitivity to stressful life events. Here we explored whether 5-HTTLPR and sex affected behavioral responses to repeated maternal separation in infant rhesus macaques. Behaviors were collected during the acute (Day 1) and the chronic (Days 2–4) phases of the separation, and the effects of duration of separation (acute vs. chronic), genotype (long/long vs. short allele), and sex (male vs. female) on behavioral responses were analyzed across four successive separations. Males increased their levels of locomotion with repeated maternal separation, whereas females exhibited an increase in frequency of self-directed behavior, a measure of “depression-like” behavior. The short-allele predicted increased environmental exploration, particularly during the chronic phase of social separation, indicative of higher arousal. In addition, the short-allele carriers were more likely to increase their levels of self-directed behavior during the chronic phase of separation, as a function of repeated exposures. These findings suggest that the short allele may increase reactivity to repeated, chronic stressors, leaving them more vulnerable to affective psychopathology, with females particularly vulnerable. En ligne : http://dx.doi.org/10.1017/S0954579411000745 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=151 [article] The serotonin transporter gene linked polymorphic region is associated with the behavioral response to repeated stress exposure in infant rhesus macaques [Texte imprimé et/ou numérique] / Simona SPINELLI, Auteur ; Melanie L. SCHWANDT, Auteur ; Stephen G. LINDELL, Auteur ; Markus HEILIG, Auteur ; Stephen J. SUOMI, Auteur ; J. Dee HIGLEY, Auteur ; David GOLDMAN, Auteur ; Christina S. BARR, Auteur . - 2012 . - p.157-165. Langues : Anglais (eng) in Development and Psychopathology > 24-1 (January 2012) . - p.157-165 Index. décimale : PER Périodiques Résumé : The short allele of the serotonin transporter linked polymorphic region (5-HTTLPR) moderates the effects of stress on vulnerability to mood and anxiety disorders. The mechanism by which this occurs may relate to differential sensitivity to stressful life events. Here we explored whether 5-HTTLPR and sex affected behavioral responses to repeated maternal separation in infant rhesus macaques. Behaviors were collected during the acute (Day 1) and the chronic (Days 2–4) phases of the separation, and the effects of duration of separation (acute vs. chronic), genotype (long/long vs. short allele), and sex (male vs. female) on behavioral responses were analyzed across four successive separations. Males increased their levels of locomotion with repeated maternal separation, whereas females exhibited an increase in frequency of self-directed behavior, a measure of “depression-like” behavior. The short-allele predicted increased environmental exploration, particularly during the chronic phase of social separation, indicative of higher arousal. In addition, the short-allele carriers were more likely to increase their levels of self-directed behavior during the chronic phase of separation, as a function of repeated exposures. These findings suggest that the short allele may increase reactivity to repeated, chronic stressors, leaving them more vulnerable to affective psychopathology, with females particularly vulnerable. En ligne : http://dx.doi.org/10.1017/S0954579411000745 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=151

Variability in post-error behavioral adjustment is associated with functional abnormalities in the temporal cortex in children with ADHD / Simona SPINELLI in Journal of Child Psychology and Psychiatry, 52-7 (July 2011)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 52-7 (July 2011) . - p.808-816 Titre : Variability in post-error behavioral adjustment is associated with functional abnormalities in the temporal cortex in children with ADHD Type de document : Texte imprimé et/ou numérique Auteurs : Simona SPINELLI, Auteur ; Roma A. VASA, Auteur ; Suresh JOEL, Auteur ; Tess E. NELSON, Auteur ; James J. PEKAR, Auteur ; Stewart H. MOSTOFSKY, Auteur Année de publication : 2011 Article en page(s) : p.808-816 Langues : Anglais (eng) Mots-clés : Error processing  variability  temporal cortex  medial frontal cortex  ADD/ADHD  child  fMRI  brain imaging  distractibility  emotion regulation  reaction time Index. décimale : PER Périodiques Résumé : Background:  Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral deficits remain unclear. The dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC) are key regions implicated in error processing and subsequent behavioral adjustment. We hypothesized that children with ADHD, compared to typically developing (TD) controls, would exhibit reduced PFC activation during post-error (versus post-correct inhibition) trials and reduced dACC activation during error (versus correct inhibition) trials. Methods:  Using functional Magnetic Resonance Imaging (fMRI) and a Go/No-Go task, we analyzed the neural correlates of error processing in 13 children with ADHD and 17 TD children. Results:  Behaviorally, children with ADHD showed similar RT slowing but increased ISV compared to controls. The post-error contrast revealed a relative increase in blood-oxygen-level dependent (BOLD) signal in the middle/inferior temporal cortex (TempC), the ACC/supplementary motor area (SMA) and the somatosensory/auditory cortex (AudC) in children with ADHD compared to controls. Importantly, in the ADHD group, increased post-error temporal cortex activity was associated with lower ISV. During error (versus correct inhibition) trials, no between-group differences were detected. However, in children with ADHD lower ISV was associated with decreased insula and increased precentral gyrus activity. Conclusions:  In children with ADHD, post-error neural activity suggests, first, a shift of attention towards task-irrelevant stimuli (AudC), and second, a recruitment of compensatory regions that resolve stimulus conflict (TempC) and improve response selection/execution (ACC/SMA). ADHD children with higher temporal cortex activation showed lower ISV, suggesting that functional abnormalities in the compensatory temporal regions contribute to increased variability. Moreover, increased ISV may be related to an over-sensitivity to negative outcomes during error trials in ADHD (insula correlation). En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02356.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=126 [article] Variability in post-error behavioral adjustment is associated with functional abnormalities in the temporal cortex in children with ADHD [Texte imprimé et/ou numérique] / Simona SPINELLI, Auteur ; Roma A. VASA, Auteur ; Suresh JOEL, Auteur ; Tess E. NELSON, Auteur ; James J. PEKAR, Auteur ; Stewart H. MOSTOFSKY, Auteur . - 2011 . - p.808-816. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 52-7 (July 2011) . - p.808-816 Mots-clés : Error processing  variability  temporal cortex  medial frontal cortex  ADD/ADHD  child  fMRI  brain imaging  distractibility  emotion regulation  reaction time Index. décimale : PER Périodiques Résumé : Background:  Error processing is reflected, behaviorally, by slower reaction times (RT) on trials immediately following an error (post-error). Children with attention-deficit hyperactivity disorder (ADHD) fail to show RT slowing and demonstrate increased intra-subject variability (ISV) on post-error trials. The neural correlates of these behavioral deficits remain unclear. The dorsal anterior cingulate cortex (ACC) and lateral prefrontal cortex (PFC) are key regions implicated in error processing and subsequent behavioral adjustment. We hypothesized that children with ADHD, compared to typically developing (TD) controls, would exhibit reduced PFC activation during post-error (versus post-correct inhibition) trials and reduced dACC activation during error (versus correct inhibition) trials. Methods:  Using functional Magnetic Resonance Imaging (fMRI) and a Go/No-Go task, we analyzed the neural correlates of error processing in 13 children with ADHD and 17 TD children. Results:  Behaviorally, children with ADHD showed similar RT slowing but increased ISV compared to controls. The post-error contrast revealed a relative increase in blood-oxygen-level dependent (BOLD) signal in the middle/inferior temporal cortex (TempC), the ACC/supplementary motor area (SMA) and the somatosensory/auditory cortex (AudC) in children with ADHD compared to controls. Importantly, in the ADHD group, increased post-error temporal cortex activity was associated with lower ISV. During error (versus correct inhibition) trials, no between-group differences were detected. However, in children with ADHD lower ISV was associated with decreased insula and increased precentral gyrus activity. Conclusions:  In children with ADHD, post-error neural activity suggests, first, a shift of attention towards task-irrelevant stimuli (AudC), and second, a recruitment of compensatory regions that resolve stimulus conflict (TempC) and improve response selection/execution (ACC/SMA). ADHD children with higher temporal cortex activation showed lower ISV, suggesting that functional abnormalities in the compensatory temporal regions contribute to increased variability. Moreover, increased ISV may be related to an over-sensitivity to negative outcomes during error trials in ADHD (insula correlation). En ligne : http://dx.doi.org/10.1111/j.1469-7610.2010.02356.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=126

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