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Purpose: In this study, the authors examined the impact of sampling context on multiple aspects of expressive language in male participants with fragile X syndrome in comparison to male participants with Down syndrome or typical development. Method: Participants with fragile X syndrome (n = 27), ages 10-17 years, were matched groupwise on nonverbal mental age to adolescents with Downs yndrome(n = 15) and typically developing 3- to 6-year-olds (n = 15). Language sampling contexts were an interview-style conversation and narration of a wordless book, with scripted examiner behavior. Language was assessed in terms of amount of talk, mean length of communication unit (MLCU), lexical diversity, fluency, and intelligibility. Results: Participants with fragile X syndrome had lower MLCU and lexical diversity than did participants with typical development. Participants with Down syndrome produced yet lower MLCU. A differential effect of context among those with fragile X syndrome, Down syndrome, and typical development emerged for the number of attempts per minute, MLCU, and fluency. For participants with fragile X syndrome, autism symptom severity related to the number of utterances produced in conversation. Aspects of examiner behavior related to participant performance. Conclusion: Sampling context characteristics should be considered when assessing expressive language in individuals with neurodevelopmental disabilities. Key Words: language sampling, conversation, narrative, fragile X syndrome, mean length of utterance (MLU), Of the methods used to assess expressive language in children and adolescents with intellectual disabilities, standardized tests and spontaneous language samples are the most often used (Abbeduto, Kover, & McDuffie, [...]

Fragile X syndrome (FXS), a common inherited form of mental impairment and autism, is caused by transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult Fmr1 knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased pairedpulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework. autism | long-term potentiation | synaptic plasticity | metabotropic glutamate receptor doi/ 10.1073/pnas.1002262107

Purpose: To compare the phonological accuracy and speech intelligibility of boys with fragile X syndrome with autism spectrum disorder (FXS-ASD), fragile X syndrome only (FXS-O), Down syndrome (DS), and typically developing (TD) boys. Method: Participants were 32 boys with FXS-O (3-14 years), 31 with FXS-ASD (5-15 years), 34 with DS (4-16 years), and 45 TD boys of similar nonverbal mental age. We used connected speech samples to compute measures of phonological accuracy, phonological process occurrence, and intelligibility. Results: The boys with FXS, regardless of autism status, did not differ from TD boys on phonological accuracy and phonological process occurrence but produced fewer intelligible words than did TD boys. The boys with DS scored lower on measures of phonological accuracy and occurrence of phonological processes than all other groups and used fewer intelligible words than did TD boys. The boys with FXS and the boys with DS did not differ on measures of intelligibility. Conclusions: Boys with FXS, regardless of autism status, exhibited phonological characteristics similar to those of younger TD children but were less intelligible in connected speech. Boys with DS showed greater delays in all phonological measures than the boys with FXS and the TD boys. KEY WORDS: fragile X syndrome, Down syndrome, autism, phonology, Fragile X syndrome (FXS) and Down syndrome (DS) are the two most common genetic causes of intellectual disability (Dykens, Hodapp, & Finucane, 2000; Hagerman & Hagerman, 2002). In addition to [...]

Fragile X syndrome, a common form of inherited mental retardation, is caused by the absence of the fragile X mental retardation protein (FMRP) due to a mutation in the FMR1 gene. We investigated the differentiation of neural stem cells generated from the brains of fmr1-knockout (KO) mice and from postmortem tissue of a fragile X fetus. Mouse and human FMRP-deficient neurospheres generated more TuJ1-positive cells (3-fold and 5-fold, respectively) than the control neurospheres generated from normal mouse and human brains, and these cells showed morphological alterations with fewer and shorter neurites and a smaller cell body volume. The number of cells expressing glial fibrillary acidic protein and generated by these neurospheres was reduced because of increased apoptotic cell death. Furthermore, there was an increase in a population of cells with intense oscillatory [Ca.sup.2+] responses to neurotransmitters in differentiated cells lacking FMRP. In addition, the number of cells in a cohort of bromodeoxyuridine-labeled newborn cells was increased in the subventricular zone of the telencephalon of the fmr1-KO mouse in vivo. These results demonstrate substantial alterations in the early maturation of FMRP-deficient neural stem cells in fragile X syndrome and in the fmr1-KO mice. fmr1 gene | fragile X mental retardation protein | neurogenesis | oscillations