1. Anderberg E, Cox JC, Neeley Tass ES, Erekson DM, Gabrielsen TP, Warren JS, Cline J, Petersen D, South M. {{Sticking with it: Psychotherapy outcomes for adults with autism spectrum disorder in a university counseling center setting}}. {Autism Res};2017 (Aug 17)
Young adults with autism spectrum disorders (ASD) experience high rates of comorbid mental health concerns in addition to distress arising from the core symptoms of autism. Many adults with ASD seek psychological treatment in outpatient facilities in their communities that are not specifically geared toward individuals with ASD. However, few studies have looked at the effectiveness of standard psychotherapeutic care in adults with ASD. This study aimed to discover how individuals with ASD fare in psychotherapy within a college counseling setting, compared to their neurotypical peers. Clients with ASD (n = 76) or possible ASD (n = 91) were retrospectively identified from counseling center case notes. Data from the Outcome Questionnaire-45 (OQ) were retrieved for each therapy session as a measure of client distress. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers (n = 21,546), and improved about the same amount from pre- to post-treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on OQ reports. Results are discussed with implications for university and other community based treatment settings. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study aimed to discover how individuals with autism spectrum disorders (ASD) fare in psychotherapy within a university counseling setting, compared to their neurotypical peers. Clients with ASD showed no difference in level of distress at intake compared to their neurotypical peers, and improved about the same amount from pre- to post-treatment. However, students with ASD stayed in treatment for significantly more sessions than neurotypical clients, and took significantly longer to achieve maximum improvement on Outcome Questionnaire-45 reports.
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2. Bailey DB, Jr., Berry-Kravis E, Gane LW, Guarda S, Hagerman R, Powell CM, Tassone F, Wheeler A. {{Fragile X Newborn Screening: Lessons Learned From a Multisite Screening Study}}. {Pediatrics};2017 (Jun);139(Suppl 3):S216-s225.
BACKGROUND: Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. METHODS: Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. RESULTS: A number of publications have resulted from the project. This article summarizes 10 « lessons learned » about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. CONCLUSIONS: The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families.
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3. Bonanni P, Casellato S, Fabbro F, Negrin S. {{Epilepsy in fragile-X-syndrome mimicking panayiotopoulos syndrome: Description of three patients}}. {Am J Med Genet A};2017 (Aug 16)
Fragile-X-syndrome is the most common cause of inherited intellectual disability. Epilepsy is reported to occur in 10-20% of individuals with Fragile-X-syndrome. A frequent seizure/electroencephalogram (EEG) pattern resembles that of benign rolandic epilepsy. We describe the clinical features, EEG findings and evolution in three patients affected by Fragile-X-syndrome and epilepsy mimicking Panayiotopoulos syndrome. Age at seizure onset was between 4 and about 7 years. Seizures pattern comprised a constellation of autonomic symptoms with unilateral deviation of the eyes and ictal syncope. Duration of the seizures could be brief or lengthy. Interictal EEGs revealed functional multifocal abnormalities. The evolution was benign in all patients with seizures remission before the age of 14. This observation expands the spectrum of benign epileptic phenotypes present in Fragile-X-syndrome and may be quite helpful in guiding anticonvulsant management and counseling families as to expectations regarding seizure remission.
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4. Boutrus M, Maybery MT, Alvares GA, Tan DW, Varcin KJ, Whitehouse AJO. {{Investigating facial phenotype in autism spectrum conditions: The importance of a hypothesis driven approach}}. {Autism Res};2017 (Aug 17)
Atypical facial characteristics have been observed in many disorders associated with developmental disability. While autism spectrum conditions (ASC) have not previously been thought to be associated with a distinct facial phenotype, an emerging research literature is casting doubt on this assumption. The identification of differences in the facial phenotype of individuals with ASC may contribute to efforts to promote early identification of the condition and help elucidate etiological pathways. With the aim of identifying facial phenotypes associated with ASC, this commentary evaluated facial features purported to distinguish ASC from typical development. Although there is little consensus across the reviewed studies for the majority of facial characteristics described, preliminary evidence suggests increased facial asymmetry may be more common in ASC. There is also evidence to suggest that there are morphologically distinct subgroups within ASC that correspond with different cognitive and behavioral symptomatology. However, in light of the various inconsistencies in the reported literature, and based on an accumulating understanding of etiological pathways proposed to be associated with ASC, we propose an alternative paradigm for investigating facial phenotypes in ASC. A series of studies are outlined to demonstrate the promise of a research program that has taken a hypothesis-driven approach to examine facial phenotypes associated with increased exposure to prenatal testosterone and to ASC. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This commentary reviewed studies that found differences in the facial features of individuals with autism spectrum conditions (ASC) compared to typically developing individuals. While there is little agreement between studies, there is some support for asymmetrical facial features associated with ASC, and preliminary evidence that particular facial features relate to specific patterns of cognitive and behavioral symptoms. However, in light of inconsistencies between studies and based on accumulating understanding of etiological pathways, we propose an alternative approach to investigating facial differences in ASC.
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5. Casellato C, Gandolla M, Crippa A, Pedrocchi A. {{Robotic set-up to quantify hand-eye behavior in motor execution and learning of children with autism spectrum disorder}}. {IEEE Int Conf Rehabil Robot};2017 (Jul);2017:953-958.
Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder characterized by a persistence of social and communication impairment, and restricted and repetitive behaviors. However, motor disorders have also been described, but not objectively assessed. Most studies showed inefficient eye-hand coordination and motor learning in children with ASD; in other experiments, mechanisms of acquisition of internal models in self-generated movements appeared to be normal in autism. In this framework, we have developed a robotic protocol, recording gaze and hand data during upper limb tasks, in which a haptic pen-like handle is moved along specific trajectories displayed on the screen. The protocol includes trials of reaching under a perturbing force field and catching moving targets, with or without visual availability of the whole path. We acquired 16 typically-developing scholar-age children and one child with ASD as a case study. Speed-accuracy tradeoff, motor performance, and gaze-hand spatial coordination have been evaluated. Compared to typically developing peers, in the force field sequence, the child with ASD showed an intact but delayed learning, and more variable gazehand patterns. In the catching trials, he showed less efficient movements, but an intact capability of exploiting the available a-priori plan. The proposed protocol represents a powerful tool, easily tunable, for quantitative (longitudinal) assessment, and for subject-tailored training in ASD.
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6. Davis JK, Broadie K. {{Multifarious Functions of the Fragile X Mental Retardation Protein}}. {Trends Genet};2017 (Aug 18)
Fragile X syndrome (FXS), a heritable intellectual and autism spectrum disorder (ASD), results from the loss of Fragile X mental retardation protein (FMRP). This neurodevelopmental disease state exhibits neural circuit hyperconnectivity and hyperexcitability. Canonically, FMRP functions as an mRNA-binding translation suppressor, but recent findings have enormously expanded its proposed roles. Although connections between burgeoning FMRP functions remain unknown, recent advances have extended understanding of its involvement in RNA, channel, and protein binding that modulate calcium signaling, activity-dependent critical period development, and the excitation-inhibition (E/I) neural circuitry balance. In this review, we contextualize 3 years of FXS model research. Future directions extrapolated from recent advances focus on discovering links between FMRP roles to determine whether FMRP has a multitude of unrelated functions or whether combinatorial mechanisms can explain its multifaceted existence.
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7. Esse Wilson J, Quinn DK, Wilson JK, Garcia CM, Tesche CD. {{Transcranial Direct Current Stimulation to the Right Temporoparietal Junction for Social Functioning in Autism Spectrum Disorder: Case Report}}. {J ect};2017 (Aug 18)
OBJECTIVES: While there is evidence of improved social functioning after applying transcranial direct current stimulation (tDCS) at the right temporoparietal junction (rTPJ) in individuals who are healthy, no current studies have investigated the use of tDCS at the rTPJ to improve social functioning in individuals with autism spectrum disorder (ASD). This case investigates the use of tDCS applied to the rTPJ to target social functioning in a high-functioning adult with ASD. METHODS: The authors present a case of an 18-year old patient with ASD treated successfully with tDCS; 1.5 mA of tDCS was applied once a day for 30 minutes for 8 consecutive days with the anode electrode over rTPJ (CP6 in the 10/10 electroencephalogram system) and the cathode electrode placed on the ipsilateral deltoid. Behavioral outcome was assessed using the Autism Treatment Evaluation Checklist prior to tDCS, after the final tDCS session, and at 2 months after tDCS. An additional, informal follow-up was also made 1 year after tDCS. RESULTS: Autism Treatment Evaluation Checklist showed substantial improvement in social functioning from baseline to post-tDCS, which was maintained at 2 months. The patient also reported lessened feelings of anger and frustration over social disappointments. Informal follow-up 1 year after stimulation indicates that the patient continues to maintain many improvements. CONCLUSIONS: Anodal tDCS to the rTPJ may represent an effective treatment for improving social functioning in ASD, with a larger clinical trial needed to validate this effect.
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8. Gogliotti RG, Senter RK, Fisher NM, Adams J, Zamorano R, Walker AG, Blobaum AL, Engers DW, Hopkins CR, Daniels JS, Jones CK, Lindsley CW, Xiang Z, Conn PJ, Niswender CM. {{mGlu7 potentiation rescues cognitive, social, and respiratory phenotypes in a mouse model of Rett syndrome}}. {Sci Transl Med};2017 (Aug 16);9(403)
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. The cognitive impairments seen in mouse models of RTT correlate with deficits in long-term potentiation (LTP) at Schaffer collateral (SC)-CA1 synapses in the hippocampus. Metabotropic glutamate receptor 7 (mGlu7) is the predominant mGlu receptor expressed presynaptically at SC-CA1 synapses in adult mice, and its activation on GABAergic interneurons is necessary for induction of LTP. We demonstrate that pathogenic mutations in MECP2 reduce mGlu7 protein expression in brain tissue from RTT patients and in MECP2-deficient mouse models. In rodents, this reduction impairs mGlu7-mediated control of synaptic transmission. We show that positive allosteric modulation of mGlu7 activity restores LTP and improves contextual fear learning, novel object recognition, and social memory. Furthermore, mGlu7 positive allosteric modulation decreases apneas in Mecp2+/- mice, suggesting that mGlu7 may be a potential therapeutic target for multiple aspects of the RTT phenotype.
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9. Golestan S, Soleiman P, Moradi H. {{Feasibility of using sphero in rehabilitation of children with autism in social and communication skills}}. {IEEE Int Conf Rehabil Robot};2017 (Jul);2017:989-994.
The majority of children with autism face difficulties in social interaction and communication skills. Consequently, in this paper we present a pilot study in which we explored the usability of SpheroTM as a rehabilitation tool for developing social and communication skills. We designed an interactive scenario where children with autism should verbally control the robot and utter voice commands. Our observations show that the children were very interested to interact with the robot in the given framework. They showed surprising behaviors that are promising evidences of effectiveness of using Sphero in rehabilitation of social and communication deficits.
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10. Hubbard DJ, Faso DJ, Assmann PF, Sasson NJ. {{Production and perception of emotional prosody by adults with autism spectrum disorder}}. {Autism Res};2017 (Aug 17)
This study examined production and perception of affective prosody by adults with autism spectrum disorder (ASD). Previous research has reported increased pitch variability in talkers with ASD compared to typically developing (TD) controls in grammatical speaking tasks (e.g., comparing interrogative vs. declarative sentences), but it is unclear whether this pattern extends to emotional speech. In this study, speech recordings in five emotion contexts (angry, happy, interested, sad, and neutral) were obtained from 15 adult males with ASD and 15 controls (Experiment 1), and were later presented to 52 listeners (22 with ASD) who were asked to identify the emotion expressed and rate the level of naturalness of the emotion in each recording (Experiment 2). Compared to the TD group, talkers with ASD produced phrases with greater intensity, longer durations, and increased pitch range for all emotions except neutral, suggesting that their greater pitch variability was specific to emotional contexts. When asked to identify emotion from speech, both groups of listeners were more accurate at identifying the emotion context from speech produced by ASD speakers compared to TD speakers, but rated ASD emotional speech as sounding less natural. Collectively, these results reveal differences in emotional speech production in talkers with ASD that provide an acoustic basis for reported perceptions of oddness in the speech presentation of adults with ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study examined emotional speech communication produced and perceived by adults with autism spectrum disorder (ASD) and typically-developing (TD) controls. Compared to the TD group, talkers with ASD produced emotional phrases that were louder, longer, and more variable in pitch. Both ASD and TD listeners were more accurate at identifying emotion in speech produced by ASD speakers compared to TD speakers, but rated ASD emotional speech as sounding less natural.
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11. Jackel C, Shults J, Wiley S, Meinzen-Derr J, Augustyn M, Blum N. {{Factors Associated with Developmental Behavioral Pediatricians Prescribing Psychotropic Medication to Children with Autism Spectrum Disorder: A Study of Three DBPNet Sites}}. {J Dev Behav Pediatr};2017 (Aug 10)
OBJECTIVE: Psychotropic medications are frequently prescribed to children with autism spectrum disorder (ASD), but little is known about the prescribing practices of developmental-behavioral pediatricians (DBPs). Our objective was to determine whether clinical site, age, insurance, or comorbidities influenced DBPs prescribing psychotropic medication for children with ASD. METHODS: A retrospective analysis was performed using electronic health record data of all patients with ASD seen at 3 academic developmental-behavioral pediatrics (DBP) clinical programs from January 2010 to December 2011. Data included age, diagnoses, primary insurance, and medications prescribed. Factors associated with prescribing psychotropic medication were examined using generalized estimating equations. RESULTS: Sites varied in the frequency with which they prescribed psychotropic medication for children with ASD (site 1: 33.1%, site 2: 49.3%, site 3: 4.0%; p < .001). We found that the following factors predicted prescribing of psychotropic medications: comorbidities (odds ratio [OR]: 2.87; 95% confidence interval [CI], 2.58-3.18), age, and primary insurance. However, the impact of insurance depended on age. For 3- to 5-year-old children, those on Medicaid were more likely to be prescribed psychotropic medications than those with private insurance (OR: 1.65; 95% CI, 1.29-2.12). This was particularly true for alpha-2-adrenergic agonists (OR: 2.48; 95% CI, 1.56-3.92) and atypical antipsychotics (OR: 2.57; 95% CI, 1.46-4.55). CONCLUSION: There are large variations in prescribing psychotropic medication to children with ASD at 3 academic DBP programs. Further research is needed to understand factors that contribute to higher use of psychotropic medication in young children with Medicaid. Lien vers le texte intégral (Open Access ou abonnement)
12. Kaufmann WE, Kidd SA, Andrews HF, Budimirovic DB, Esler A, Haas-Givler B, Stackhouse T, Riley C, Peacock G, Sherman SL, Brown WT, Berry-Kravis E. {{Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment}}. {Pediatrics};2017 (Jun);139(Suppl 3):S194-s206.
BACKGROUND AND OBJECTIVE: Individuals with fragile X syndrome (FXS) are frequently codiagnosed with autism spectrum disorder (ASD). Most of our current knowledge about ASD in FXS comes from family surveys and small studies. The objective of this study was to examine the impact of the ASD diagnosis in a large clinic-based FXS population to better inform the care of people with FXS. METHODS: The study employed a data set populated by data from individuals with FXS seen at specialty clinics across the country. The data were collected by clinicians at the patient visit and by parent report for nonclinical and behavioral outcomes from September 7, 2012 through August 31, 2014. Data analyses were performed by using chi2 tests for association, t tests, and multiple logistic regression to examine the association between clinical and other factors with ASD status. RESULTS: Half of the males and nearly 20% of females met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for current ASD. Relative to the FXS-only group, the FXS with ASD (FXS+ASD) group had a higher prevalence of seizures (20.7% vs 7.6%, P < .001), persistence of sleep problems later in childhood, increased behavior problems, especially aggressive/disruptive behavior, and higher use of alpha-agonists and antipsychotics. Behavioral services, including applied behavior analysis, appeared to be underused in children with FXS+ASD (only 26% and 16% in prekindergarten and school-age periods, respectively) relative to other populations with idiopathic ASD. CONCLUSIONS: These findings confirm among individuals with FXS an association of an ASD diagnosis with important cooccurring conditions and identify gaps between expected and observed treatments among individuals with FXS+ASD. Lien vers le texte intégral (Open Access ou abonnement)
13. Prasad H, Osei-Owusu J, Rao R. {{Functional analysis of Na+/H+ exchanger 9 variants identified in patients with autism and epilepsy}}. {Matters (Zur)};2017 (Apr);2017
Na+/H+ exchanger isoform 9, NHE9, finely tunes the pH within the endosomal lumen to regulate cargo trafficking and turnover. In patients with autism, genetic approaches have revealed deletions, truncations and missense mutations in the gene encoding NHE9 (SLC9A9). To help establish causality, functional evaluation is needed to distinguish pathogenic mutations from harmless polymorphisms. Here, we evaluated three previously uncharacterized NHE9 variants, P117T, D496N, and Q609K reported in patients with autism and epilepsy. We show that NHE9-DsRed localizes to recycling endosomes in HEK293 cells where it significantly alkalinizes luminal pH, and elevates accumulation of transferrin. All three NHE9 variants were expressed and localized to endosomal compartments, similar to wild-type NHE9. In contrast to previously characterized NHE9 variants, we observed no loss-of-function with respect to endosomal pH homeostasis and transferrin endocytosis. These findings suggest that the three NHE9 substitutions analyzed in our study are either benign polymorphisms or may have a cell-type specific or regulatory function not detected in our cell culture model. Our findings highlight the importance of combining the use of cellular studies of function with sequencing technologies that capture genomic variation in patients.
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14. Raspa M, Wheeler AC, Riley C. {{Public Health Literature Review of Fragile X Syndrome}}. {Pediatrics};2017 (Jun);139(Suppl 3):S153-s171.
OBJECTIVES: The purpose of this systematic literature review is to describe what is known about fragile X syndrome (FXS) and to identify research gaps. The results can be used to help inform future public health research and provide pediatricians with up-to-date information about the implications of the condition for individuals and their families. METHODS: An electronic literature search was conducted, guided by a variety of key words. The search focused on 4 areas of both clinical and public health importance: (1) the full mutation phenotype, (2) developmental trajectories across the life span, (3) available interventions and treatments, and (4) impact on the family. A total of 661 articles were examined and 203 were included in the review. RESULTS: The information is presented in the following categories: developmental profile (cognition, language, functional skills, and transition to adulthood), social-emotional profile (cooccurring psychiatric conditions and behavior problems), medical profile (physical features, seizures, sleep, health problems, and physiologic features), treatment and interventions (educational/behavioral, allied health services, and pharmacologic), and impact on the family (family environment and financial impact). Research gaps also are presented. CONCLUSIONS: The identification and treatment of FXS remains an important public health and clinical concern. The information presented in this article provides a more robust understanding of FXS and the impact of this complex condition for pediatricians. Despite a wealth of information about the condition, much work remains to fully support affected individuals and their families.
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15. Reinvall O, Kujala T, Voutilainen A, Moisio AL, Lahti-Nuuttila P, Laasonen M. {{Sluggish cognitive tempo in children and adolescents with higher functioning autism spectrum disorders: Social impairments and internalizing symptoms}}. {Scand J Psychol};2017 (Aug 16)
Sluggish cognitive tempo (SCT) was introduced in 1980s in the field of attention deficit hyperactivity disorder (ADHD). Studies indicate that symptoms of SCT are separate from symptoms of ADHD and independently associated with multiple domains of functioning in clinical groups and in typical development. We assessed whether similar pattern would apply to higher functioning autism spectrum disorders (ASD). Children with higher functioning ASD (N = 55; 5-15 years) were divided into the ASD+High SCT (n = 17), the ASD+Medium SCT (n = 18) and the ASD+Low SCT (n = 20) groups based on parent-rated daydreaming and slowness on the Five to Fifteen questionnaire (FTF). The groups were compared on SCT-related impairments found in previous studies: social skills, academic functioning, psychiatric symptoms, and processing speed. Assessment methods were the FTF, the Development and Well-Being Assessment, and the Coding subtest of the WISC-III. The ADHD symptoms were statistically controlled due to the overlap between SCT and ADHD. The ASD+High SCT and ASD+Medium SCT groups were significantly more likely to have the most pronounced social impairments, and the ASD+High SCT group had significantly higher rate of internalizing disorders compared to the ASD+Low SCT group. Our results suggest that children with higher functioning ASD and high or medium levels of SCT symptoms could be at higher risk for psychosocial impairments than children with higher functioning ASD with low levels of SCT symptoms. Co-occurring ADHD symptoms do not explain the finding. Recognizing SCT symptoms in higher functioning ASD would be important to targeting preventive support.
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16. Riley C, Mailick M, Berry-Kravis E, Bolen J. {{The Future of Fragile X Syndrome: CDC Stakeholder Meeting Summary}}. {Pediatrics};2017 (Jun);139(Suppl 3):S147-s152.
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17. Riley C, Wheeler A. {{Assessing the Fragile X Syndrome Newborn Screening Landscape}}. {Pediatrics};2017 (Jun);139(Suppl 3):S207-s215.
BACKGROUND: Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. METHODS: A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. RESULTS: The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. CONCLUSIONS: The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life.
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18. Sherman SL, Kidd SA, Riley C, Berry-Kravis E, Andrews HF, Miller RM, Lincoln S, Swanson M, Kaufmann WE, Brown WT. {{FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome}}. {Pediatrics};2017 (Jun);139(Suppl 3):S183-s193.
BACKGROUND AND OBJECTIVE: Advances in the care of patients with fragile X syndrome (FXS) have been hampered by lack of data. This deficiency has produced fragmentary knowledge regarding the natural history of this condition, healthcare needs, and the effects of the disease on caregivers. To remedy this deficiency, the Fragile X Clinic and Research Consortium was established to facilitate research. Through a collective effort, the Fragile X Clinic and Research Consortium developed the Fragile X Online Registry With Accessible Research Database (FORWARD) to facilitate multisite data collection. This report describes FORWARD and the way it can be used to improve health and quality of life of FXS patients and their relatives and caregivers. METHODS: FORWARD collects demographic information on individuals with FXS and their family members (affected and unaffected) through a 1-time registry form. The longitudinal database collects clinician- and parent-reported data on individuals diagnosed with FXS, focused on those who are 0 to 24 years of age, although individuals of any age can participate. RESULTS: The registry includes >2300 registrants (data collected September 7, 2009 to August 31, 2014). The longitudinal database includes data on 713 individuals diagnosed with FXS (data collected September 7, 2012 to August 31, 2014). Longitudinal data continue to be collected on enrolled patients along with baseline data on new patients. CONCLUSIONS: FORWARD represents the largest resource of clinical and demographic data for the FXS population in the United States. These data can be used to advance our understanding of FXS: the impact of cooccurring conditions, the impact on the day-to-day lives of individuals living with FXS and their families, and short-term and long-term outcomes.
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19. Sjaarda CP, Hecht P, McNaughton AJM, Zhou A, Hudson ML, Will MJ, Smith G, Ayub M, Liang P, Chen N, Beversdorf D, Liu X. {{Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development}}. {Sci Rep};2017 (Aug 18);7(1):8735.
The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon. Restraint stress was applied to pregnant Slc6a4 +/+ and Slc6a4 +/- mice and post-stress embryonic brains were assessed for whole genome level profiling of methylome, transcriptome and miRNA using Next Generation Sequencing. Embryos of stressed Slc6a4 +/+ dams exhibited significantly altered methylation profiles and differential expression of 157 miRNAs and 1009 genes affecting neuron development and cellular adhesion pathways, which may function as a coping mechanism to prenatal stress. In striking contrast, the response of embryos of stressed Slc6a4 +/- dams was found to be attenuated, shown by significantly reduced numbers of differentially expressed genes (458) and miRNA (0) and genome hypermethylation. This attenuated response may pose increased risks on typical brain development resulting in development of ASD-like characteristics in offspring of mothers with deficits in serotonin related pathways during stressful pregnancies.
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20. Ueda K, Sood S, Asano E, Kumar A, Luat AF. {{Elimination of medically intractable epileptic drop attacks following endoscopic total corpus callosotomy in Rett syndrome}}. {Childs Nerv Syst};2017 (Aug 16)
INTRODUCTION: Rett syndrome is a neurodevelopmental genetic disorder, characterized by developmental delay, hand stereotypies, abnormal gait, and acquired microcephaly. Epilepsy is very common in Rett syndrome and can be medically intractable. It remains uncertain if a patient with epileptic drop attacks associated with this genetic disease can benefit from corpus callosotomy. CASE REPORT: We report an 8-year-old girl with Rett syndrome and medically intractable epileptic drop attacks who underwent endoscopic total corpus callosotomy without any complications that led to the successful elimination of her seizures. CONCLUSION: Total corpus callosotomy is a feasible treatment option for medically intractable epileptic drop attacks in Rett syndrome and should not be considered as a contraindication in this condition. This is the first reported case of corpus callosotomy in Rett syndrome.
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21. Upthegrove R, Abu-Akel A, Chisholm K, Lin A, Zahid S, Pelton M, Apperly I, Hansen PC, Wood SJ. {{Autism and psychosis: Clinical implications for depression and suicide}}. {Schizophr Res};2017 (Aug 18)
There is increasing recognition of the co-occurrence of autism and schizophrenia spectrum disorders. However, the clinical significance of this on outcomes such as depression and suicidal thinking has not been explored. This study examines the association of autism spectrum traits, depressive symptoms and suicidal behaviour in individuals with psychotic experiences. In two cross sectional studies, individuals from a non-help seeking university student sample and patients with first episode psychosis (FEP) service completed standardized measures of autism spectrum traits, psychotic experiences, depressive symptoms and suicidal thinking. In healthy non-help seeking students, increased autism traits and increased subclinical psychotic experiences were significantly associated with depressive symptoms; a significant interaction effect suggests their combined presence has a greater impact on depression. In FEP, high autism traits and positive symptoms were associated with increased depression, hopelessness and suicidality, however there was no significant interaction effect. In FEP a multiple mediation model revealed that the relationship between autism traits and risk for suicidality was mediated through hopelessness. Young people with subclinical psychotic experiences and all patients with FEP should be screened for autism spectrum traits, which may have significant impact on clinical outcomes. Tailored interventions for patients with high levels of autistic spectrum co-morbidities in FEP should be a priority for future research.
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22. Wheeler A, Raspa M, Hagerman R, Mailick M, Riley C. {{Implications of the FMR1 Premutation for Children, Adolescents, Adults, and Their Families}}. {Pediatrics};2017 (Jun);139(Suppl 3):S172-s182.
BACKGROUND AND OBJECTIVES: Given the nature of FMR1 gene expansions, most biological mothers, and often multiple other family members of children with fragile X syndrome (FXS), will have a premutation, which may increase individual and family vulnerabilities. This article summarizes important gaps in knowledge and notes potential implications for pediatric providers with regard to developmental and medical risks for children and adolescents with an FMR1 premutation, including possible implications into adulthood. METHODS: A structured electronic literature search was conducted on FMR1 pre- and full mutations, yielding a total of 306 articles examined. Of these, 116 focused primarily on the premutation and are included in this review. RESULTS: Based on the literature review, 5 topic areas are discussed: genetics and epidemiology; phenotypic characteristics of individuals with the premutation; implications for carrier parents of children with FXS; implications for the extended family; and implications for pediatricians. CONCLUSIONS: Although the premutation phenotype is typically less severe in clinical presentation than in FXS, premutation carriers are much more common and are therefore more likely to be seen in a typical pediatric practice. In addition, there is a wide range of medical, cognitive/developmental, and psychiatric associated features that individuals with a premutation are at increased risk for having, which underscores the importance of awareness on the part of pediatricians in identifying and monitoring premutation carriers and recognizing the impact this identification may have on family members.
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23. Youssef EA, Berry-Kravis E, Czech C, Hagerman RJ, Hessl D, Wong CY, Rabbia M, Deptula D, John A, Kinch R, Drewitt P, Lindemann L, Marcinowski M, Langland R, Horn C, Fontoura P, Santarelli L, Quiroz JA. {{Effect of the mGluR5-NAM Basimglurant on Behavior in Adolescents and Adults with Fragile X Syndrome in a Randomized, Double-Blind, Placebo-Controlled Trial: FragXis Phase 2 Results}}. {Neuropsychopharmacology};2017 (Aug 17)
Preclinical data suggests that inhibition of the mGluR5 receptor might hold therapeutic benefits in Fragile X syndrome (FXS). Treatment of Fmr1 knockout mice with mGluR5-negative allosteric modulators (NAMs) has been reported to correct a broad range of phenotypes related to FXS. The early short-term clinical trials with mGluR5 NAMs, including basimglurant, assessing the effects in individuals with FXS, were supportive of further exploration in larger, well-controlled trials. We evaluated basimglurant, a potent and selective mGluR5 NAM, in a 12-week, double-blind, parallel-group study of 183 adults and adolescents (aged 14-50, mean 23.4 years) with FXS. Individuals with an FMR1 full mutation were randomized to placebo or one of two doses of basimglurant. The primary efficacy endpoint was the change from baseline in behavioral symptoms using the Anxiety Depression and Mood Scale (ADAMS) total score. All treatment arms showed marked behavioral improvements from baseline to week 12 with less improvement in the basimglurant 1.5 mg arm than placebo; however, basimglurant 0.5 mg was inferior to placebo in the ADAMs total score. Treatment with basimglurant was overall well-tolerated. A higher incidence of adverse events classified as psychiatric disorders were reported in patients treated with basimglurant, including three patients with hallucinations or psychosis. In this phase 2 clinical trial, basimglurant did not demonstrate improvement over placebo. Evaluation of the overall risk-benefit in younger patient populations is an important consideration for the design of potential further investigations of efficacy with this class of medications.Neuropsychopharmacology accepted article preview online, 17 August 2017. doi:10.1038/npp.2017.177.
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24. Zeleke WA, Hughes T, Chitiyo M. {{The Path to an Autism Spectrum Disorders Diagnosis in Ethiopia: Parent Perspective}}. {Am J Orthopsychiatry};2017 (Aug 17)
This study explores the common characteristics of children with autism spectrum disorders (ASDs) and the available diagnostic and intervention currently practiced for children with ASDs in Ethiopia based on parents’ experience. Data gathered from 100 parents in Ethiopia detail the difficulties families face when they suspect their child has an autism spectrum disorder (ASD). The data indicate Ethiopian parents pursued a diagnosis of ASD after noting common ASD behaviors such as hand flapping and unusual attachments to objects. Poor social interactions were the least likely to symptoms to prompt an ASD evaluation. The large majority of parents indicated they were unaware of the services provided to their children and indicated poor parent-agency coordination. Parents noted very limited formal support systems to help cope with the stigma of having a child with ASD. Implication for future research and intervention are discussed. (PsycINFO Database Record
