The effect of early life stress on the cognitive phenotype of children with an extra X chromosome (47,XXY/47,XXX)

Studies on gene–environment interactions suggest that some individuals may be more susceptible to life adversities than others due to their genetic profile. This study assesses whether or not children with an extra X chromosome are more vulnerable to the negative impact of early life stress on cognitive functioning than typically-developing children.

A total of 50 children with an extra X chromosome and 103 non-clinical controls aged 9 to 18 years participated in the study. Cognitive functioning in domains of language, social cognition and executive functioning were assessed. Early life stress was measured with the Questionnaire of Life Events. High levels of early life stress were found to be associated with compromised executive functioning in the areas of mental flexibility and inhibitory control, irrespective of group membership. In contrast, the children with an extra X chromosome were found to be disproportionally vulnerable to deficits in social cognition on top of executive dysfunction, as compared to typically-developing children. Within the extra X group the number of negative life events is significantly correlated with more problems in inhibition, mental flexibility and social cognition. It is concluded that children with an extra X chromosome are vulnerable to adverse life events, with social cognition being particularly impacted in addition to the negative effects on executive functioning. The findings that developmental outcome is codependent on early environmental factors in genetically vulnerable children also underscores opportunities for training and support to positively influence the course of development.     

Subregion-specific dendritic spine abnormalities in the hippocampus of Fmr1 KO mice

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and is caused by the lack of fragile X mental retardation protein (FMRP). In the brain, spine abnormalities have been reported in both patients with FXS and Fmr1 knockout mice. This altered spine morphology has been linked to disturbed synaptic transmission related to altered signaling in the excitatory metabotropic glutamate receptor 5 (mGluR5) pathway. We investigated hippocampal protrusion morphology in adult Fmr1 knockout mice. Our results show a hippocampal CA1-specific altered protrusion phenotype, which was absent in the CA3 region of the hippocampus. This suggests a subregion-specific function of FMRP in synaptic plasticity in the brain.     

The perception of biological and mechanical motion in female fragile X premutation carriers

Previous studies reported impaired visual information processing in patients with fragile X syndrome and in premutation carriers. In this study, we assessed the perception of biological motion (a walking point-light character) and mechanical motion (a rotating shape) in 25 female fragile X premutation carriers and in 20 healthy non-carrier controls. Stimuli were moving stimulus dots embedded among a cloud of noise dots. Sensitivity (d′) for motion detection was determined. Emotional symptoms were assessed by Hamilton’s depression and anxiety rating scales. Results revealed that the premutation carriers displayed lower sensitivities for biological and mechanical motion relative to the non-carriers. This deficit was more pronounced in the case of biological stimuli. The premutation carriers displayed higher depression and anxiety scores relative to the non-carriers. Higher depression, but not anxiety, scores were associated with decreased sensitivity for biological, but not mechanical, motion in the carrier group. These results suggest that motion perception deficits are detectable in fragile X premutation carriers, and that the impairment of biological motion perception is associated with depressive symptoms.     

Is Theory of Mind Understanding Impaired in Males with Fragile X Syndrome?

Males with fragile X syndrome (FXS) have difficulties with social interaction and many show autistic features. This study examined whether the social deficits characteristic of FXS are associated with theory of mind difficulties. Two groups of boys with FXS participated: a group with few autistic features and a group with many autistic features. An intellectual disability control group also participated. In addition to using standard theory of mind tasks, new techniques were used that were able to separate out the various processing demands of the task (e.g., memory, inhibitory control). Overall, the findings indicate that both groups of boys with FXS have difficulty with theory of mind tasks compared to an intellectual disability control group. However, both groups with FXS also performed worse on comparison trials that required working memory but not theory of mind. Theory of mind difficulties are likely to be an important aspect of the FXS clinical profile, but are most likely the result from a more basic difficulty with working memory.     

Trace decay and the priming of short-term memory in long-delay taste aversion learning: Disruptive effects of novel exteroceptive stimulation

A variation of Kalat and Rozin's two-presentation paradigm was used to test the hypothesis that the first, as opposed to the second, presentation of a flavor conditioned stimulus (CS) constitutes the functional CS in two-presentation experiments involving moderate interflavor intervals (IFIs), and results in flavor aversions that are a function of the primary, as opposed to the secondary, conditioned stimulus-unconditioned stimulus (CS-US) interval. Contrary to the hypothesis, it was shown in Experiment 1 that holding the primary CS-US interval constant at 4 hr for each of three groups, while decreasing the secondary CS-US interval (i.e., the interval between the second flavor presentation and the illness) from 3.75 hr to 2.5 hr to .5 hr, resulted in the flavor aversion increasing as the secondary CS-US interval decreased. However, the aversion acquired by the group with a 0.5 hr secondary CS-US interval was also found to be significantly weaker than that acquired by a single-presentation 0.5 hr control group. In Experiment 2 it was demonstrated that animals exposed to novel exteroceptive stimulation (NES) immediately prior to a second flavor presentation that preceded the US by 0.5 hr acquired an aversion as strong as that acquired by a 0.5-hr control group. In Experiment 3 it was demonstrated that, in the absence of a second flavor presentation, animals exposed to novel exteroceptive stimulation 0.5 hr prior to the US acquired a weaker flavor aversion than did animals not exposed to novel exteroceptive stimulation during the 4-hr flavor CS-illness US interval. The contrasting effects of novel exteroceptive stimulation observed in Experiments 2 and 3 were replicated in Experiment 4. The results suggest, consistent with the trace-decay hypothesis and Wagner's (1976) general model of stimulus processing, that exposure to novel exteroceptive stimulation disrupts continued processing of the short-term memory (STM) trace of the initial presentation of a flavor CS, and hence minimizes stimulus preexposure effects attributable to the priming of STM.     

Hemispheric lateralization in 47,XXY Klinefelter's syndrome boys

Thirty-two boys with a 47,XXY karyotype were compared with chromosomally normal male controls in their performance on six tasks of hemispheric specialization. The results revealed that the 47,XXY subjects had smaller asymmetries on left hemisphere tasks and larger asymmetries on right hemisphere tasks than controls. Analyses of individual right and left side scores revealed that the atypical lateral asymmetries of the 47,XXYs were due to a shift toward greater right hemisphere involvement on four of the six measures. It was postulated that the slower fetal growth rates of the extra X chromosome group might contribute to their atypical hemispheric specialization and the failure of their left hemisphere to gain dominance over their right in language processing.     

Effects of induced elation-depression on the accessibility of memories of happy and unhappy experiences

Elated and depressed moods were induced in student volunteers on separate occasions. On each occasion they retrieved past real-life experiences associated to stimulus words presented. Subjects subsequently rated the experiences for happiness-unhappiness and pleasantness-unpleasantness on a third occasion in a neutral mood state. Extremely unhappy memories were significantly more likely to be retrieved in the depressed mood than in the elated mood. Extremely happy memories were significantly more likely to be retrieved in the elated mood than in the depressed mood. Measures of latency of retrieval showed a significant interaction between mood state and type of memory. The results confirm the generality of previous findings in suggesting an effect of mood state on the accessibility of different types of cognition. The results are considered in relation to mood as a context in contextual-specific encoding and retrieval, and in relation to models and treatment of clinical conditions.     

The trajectory of mathematics skills and working memory thresholds in girls with fragile X syndrome

Fragile X syndrome is a common genetic disorder associated with executive function deficits and poor mathematics achievement. In the present study, we examined changes in math performance during the elementary and middle school years in girls with fragile X syndrome, changes in the working memory loads under which children could complete a cognitive switching task, and the association between these two areas of function, in girls with fragile X syndrome relative to their peers. Our findings indicate that the trajectory of math and executive function skills of girls with fragile X differs from that of their peers and that these skills contribute to predicting math achievement and growth in math performance over time. Also, changes in math performance were associated with incremental increases in working memory demands, suggesting that girls with fragile X have a lower threshold for being able to perform under increasing task demands. Still, we found improvement in executive function performance between 10 and 12 years in girls with fragile X rather than a performance plateau as has been reported in other studies. The findings implicate the importance of early intervention in mathematics for girls with fragile X that addresses poor calculation skills, the supporting numerical skills, and deficits in executive functions, including working memory.     

A narrative synthesis of the applicability of the CaR–FA–X model in child and adolescent populations: a systematic review

The CaR–FA–X model [Williams, J. M. G., Barnhofer, T., Crane, C., Hermans, D., Raes, F., Watkins, E.,?…?Dalgleish, T. (2007). Autobiographical memory specificity and emotional disorder. Psychological Bulletin, 133(1), 122–148. doi:10.1037/0033-2909.133.1.122] is the most prominent and comprehensive model of overgeneral autobiographical memory (OGM) and provides a framework for OGM. The model comprises of three mechanisms, capture and rumination, functional avoidance and impaired executive control. These can independently, or in interaction, account for OGM. This systematic review aims to evaluate the existing research on the CaR–FA–X model, and trauma exposure studies specific to child and adolescent populations. The following databases were searched: “PsychInfo”, “PsychArticles”, “PubMed”, “Web of Science”, “Medline”, “SCOPUS” and “Embase” for English-language, peer-reviewed papers with samples <M?=?18 years, published since 1986. Support was reported for a relationship between trauma exposure and OGM as well as for capture errors and OGM. Limited support was found for rumination, avoidance and impaired executive control in isolation. No support was found for interacting mechanisms and OGM. Partial support for the CaR–FA–X model was found for child and adolescent populations. Recommendations, proposals for future research and plausible explanations for the mixed findings are discussed.