1. Balestrieri E, Cipriani C, Matteucci C, Capodicasa N, Pilika A, Korca I, Sorrentino R, Argaw-Denboba A, Bucci I, Miele MT, Coniglio A, Alessandrelli R, Vallebona PS. {{Transcriptional activity of human endogenous retrovirus in Albanian children with autism spectrum disorders}}. {New Microbiol};2016 (Jul);39(3):228-231.
Recent studies suggest that autism spectrum disorders (ASD) result from interactions between genetic and environmental factors, whose possible links could be represented by epigenetic mechanisms. Here, we investigated the transcriptional activity of three human endogenous retrovirus (HERV) families, in peripheral blood mononuclear cells (PBMCs) from Albanian ASD children, by quantitative real-time PCR. We aimed to confirm the different expression profile already found in Italian ASD children, and to highlight any social and family health condition emerging from information gathered through a questionnaire, to be included among environmental risk factors. The presence of increased HERV-H transcriptional activity in all autistic patients could be understood as a constant epigenetic imprinting of the disease, potentially useful for early diagnosis and for the development of effective novel therapeutic strategies.
2. Bassett E, Heinle R, Johnston D. {{Sleep Apnea in Patients With Rett Syndrome: Roles for Polysomnography and Adenotonsillectomy}}. {J Child Neurol};2016 (Oct 4)
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3. Hegarty JP, 2nd, Ferguson BJ, Zamzow RM, Rohowetz LJ, Johnson JD, Christ SE, Beversdorf DQ. {{Beta-adrenergic antagonism modulates functional connectivity in the default mode network of individuals with and without autism spectrum disorder}}. {Brain Imaging Behav};2016 (Oct 6)
The beta-adrenergic antagonist propranolol benefits some social and communication domains affected in autism spectrum disorder (ASD), and these benefits appear to be associated with increased functional connectivity (FC) in the brain during task performance. FC is implicated in ASD, with the majority of studies suggesting long distance hypo-connectivity combined with regionally specific local hyper-connectivity. The objective in the current investigation was to examine the effect of propranolol on FC at rest and determine whether ASD-specific effects exist. Participants with and without ASD attended three sessions in which propranolol, nadolol (a beta-adrenergic antagonist that does not cross the blood-brain barrier), or placebo were administered. Resting-state fMRI data were acquired, and graph theory techniques were utilized to assess additional aspects of FC. Compared to placebo, propranolol administration was associated with decreased FC in the dorsal medial prefrontal cortex subnetwork of the default mode network and increased FC in the medial temporal lobe subnetwork, regardless of diagnosis. These effects were not seen with nadolol suggesting that the alterations in FC following propranolol administration were not exclusively due to peripheral cardiovascular effects. Thus, beta-adrenergic antagonism can up- or down- regulate FC, depending on the network, and alter coordinated functional activation in the brain. These changes in information processing, as demonstrated by FC, may mediate some of the clinical and behavioral effects of beta-adrenergic antagonism previously reported in patients with ASD.
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4. Helles A, Wallinius M, Gillberg IC, Gillberg C, Billstedt E. {{Asperger syndrome in childhood – personality dimensions in adult life: temperament, character and outcome trajectories}}. {BJPsych Open};2016 (May);2(3):210-216.
BACKGROUND: Temperament and character have been shown to be important factors in understanding psychiatric and neurodevelopmental disorder. Adults with autism spectrum disorder (ASD) have repeatedly been shown to have a distinct temperament and character, but this has not been evaluated in relation to psychiatric comorbidity and ASD diagnostic stability. AIMS: To examine temperament and character in males that were diagnosed with ASD in childhood and followed prospectively over almost two decades. METHOD: Temperament and character were assessed in 40 adult males with a childhood diagnosis of ASD. Results were analysed by the stability of ASD diagnosis over time and current psychiatric comorbidity. RESULTS: Three distinct temperament and character profiles emerged from the data. Those no longer meeting criteria for ASD had high reward dependence while those with a stable ASD diagnosis and psychiatric comorbidity showed elevated harm avoidance and low self-directedness and cooperativeness. Finally, those with a stable ASD and no comorbidity showed low novelty seeking and somewhat elevated harm avoidance. CONCLUSIONS: Temperament and character are important factors correlated with long-term diagnostic stability and psychiatric comorbidity in males diagnosed with ASD in childhood. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
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5. Hilton CL, Babb-Keeble A, Westover EE, Zhang Y, Adams C, Collins DM, Karmarkar A, Reistetter TA, Constantino JN. {{Sensory Responsiveness in Siblings of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2016 (Oct 4)
This study examined sensory responsiveness in unaffected siblings of children with autism spectrum disorder (ASD) and associations between sensory responsiveness and social severity. Sensory Profile Caregiver Questionnaires and Social Responsiveness Scales were completed by parents of 185 children between age 4 and 10.95 years. Significant differences were found between participants with ASD and controls, and between participants with ASD and unaffected siblings for all sensory quadrants and domains, but not between controls and unaffected siblings. Social responsiveness scores were significantly correlated with scores from most sensory profile categories. Sensory responsiveness as an endophenotype of ASD is not indicated from these findings; however, studies with larger numbers of unaffected siblings and controls are needed to confirm the null hypothesis.
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6. Iacono T, Trembath D, Erickson S. {{The role of augmentative and alternative communication for children with autism: current status and future trends}}. {Neuropsychiatr Dis Treat};2016;12:2349-2361.
BACKGROUND: Augmentative and alternative communication (AAC) interventions are used for children with autism, often as stand-alone communication interventions for those who are minimally verbal. Our aim was to synthesize the evidence for AAC interventions for children (up to 21 years), and then consider the role of AAC within established, comprehensive, evidence-based autism interventions targeting learning across multiple developmental domains. DESIGN: We completed a systematic search of three databases (OVID Medline, PsycINFO, ERIC) as well as forward citation and hand searches to identify systematic reviews of AAC intervention efficacy research including children with autism, published between 2000 and March 2016 in peer-reviewed journals. Data pertaining to the quality indicators of included studies, effect sizes for intervention outcomes, and evidence for effectiveness were extracted for descriptive analysis. RESULTS: The search yielded 17 systematic reviews. Most provided indicators of research quality for included studies, of which only relatively few provided conclusive results. Communication targets tended to be focused on teaching children to make requests. Still, effect size measures for included studies indicated that AAC was effective to highly effective. CONCLUSION: There is growing evidence for the potential benefits of AAC for children with autism, but there is a need for more well-designed studies and broader, targeted outcomes. Furthermore, a lack of evidence for the role of AAC within comprehensive intervention programs may account for a tendency by autism researchers and practitioners to neglect this intervention. Attempts to compare evidence for AAC with other interventions for children with autism, including those in which the use of AAC is delayed or excluded in pursuit of speech-only communication, must take into account the needs of children with the most significant learning needs. These children pose the greatest challenges to achieving large and consistent intervention effects, yet stand to gain the most from AAC interventions.
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7. Ida-Eto M, Hara N, Ohkawara T, Narita M. {{Mechanism of auditory hypersensitivity in human autism using autism model rats}}. {Pediatr Int};2016 (Oct 5)
BACKGROUND: Auditory hypersensitivity is one of the major complications accompanied by autism spectrum disorders. The aim of this study is to investigate whether auditory brain center is affected in autism model rats. METHODS: Autism model rats were prepared by prenatal exposure to thalidomide, which is administered to embryonic day 9 and 10 of pregnant rats. Superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. RESULTS: In autism model rats, immunoreactivity of SOC was markedly decreased. Strength of immunostaining of auditory fibers in SOC was also weak in autism model rats. Surprisingly, when measured the size of medial nucleus of trapezoid body (MNTB), a nucleus exerting inhibitory function in SOC, the size of MNTB was significantly decreased in autism model rats. CONCLUSIONS: These results indicate that auditory hypersensitivity may be, in part, due to impairment of inhibitory processing exerted by auditory brain center. This article is protected by copyright. All rights reserved.
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8. Johansen A, Rosti RO, Musaev D, Sticca E, Harripaul R, Zaki M, Caglayan AO, Azam M, Sultan T, Froukh T, Reis A, Popp B, Ahmed I, John P, Ayub M, Ben-Omran T, Vincent JB, Gleeson JG, Abou Jamra R. {{Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features}}. {Am J Hum Genet};2016 (Oct 6);99(4):912-916.
The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysophosphatidylinositol acyltransferase (LPIAT1). Subjects presented with ID frequently accompanied by epilepsy and autistic features. LPIAT1 is a membrane-bound phospholipid-remodeling enzyme that transfers arachidonic acid (AA) to lysophosphatidylinositol to produce AA-containing phosphatidylinositol. This study suggests a role for AA-containing phosphatidylinositols in the development of ID accompanied by epilepsy and autistic features.
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9. Kishimoto N, Yamamuro K, Iida J, Ota T, Tanaka S, Kyo M, Kimoto S, Kishimoto T. {{Distinctive Rorschach profiles of young adults with schizophrenia and autism spectrum disorder}}. {Neuropsychiatr Dis Treat};2016;12:2403-2410.
OBJECTIVE: The differential diagnosis of schizophrenia (SZ) versus autism spectrum disorder (ASD) can be clinically challenging because accumulating evidence suggests both clinical and biological overlaps between them. The aim of this study was to compare Rorschach profiles between young adults with SZ and those with ASD. METHODS: We evaluated quantitative tendencies on the Rorschach test among 20 patients diagnosed with SZ and 20 diagnosed with ASD. Both groups were matched for age, sex, and intelligence quotient. RESULTS: We found significant differences in six response variables on the Rorschach comprehensive system. Those with SZ had significantly higher scores on D score, adjusted D score (Adj D), developmental quality code reflecting ordinary response (DQo), and form quality minus (FQ -) than those with ASD. In contrast, those with SZ had significantly lower scores on the active and developmental quality code reflecting synthesized response (DQ+) subscales than those with ASD. CONCLUSION: The present findings reveal that individuals with SZ might have more stress tolerance, stronger perception distortions, and simpler and poorer recognition than those with ASD. We suggest that the Rorschach test might be a useful tool for differentiating between SZ and ASD.
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10. Langdon PE, Murphy GH, Shepstone L, Wilson EC, Fowler D, Heavens D, Malovic A, Russell A, Rose A, Mullineaux L. {{The People with Asperger syndrome and anxiety disorders (PAsSA) trial: a pilot multicentre, single-blind randomised trial of group cognitive-behavioural therapy}}. {BJPsych Open};2016 (Mar);2(2):179-186.
BACKGROUND: There is a growing interest in using cognitive-behavioural therapy (CBT) with people who have Asperger syndrome and comorbid mental health problems. AIMS: To examine whether modified group CBT for clinically significant anxiety in an Asperger syndrome population is feasible and likely to be efficacious. METHOD: Using a randomised assessor-blind trial, 52 individuals with Asperger syndrome were randomised into a treatment arm or a waiting-list control arm. After 24 weeks, those in the waiting-list control arm received treatment, while those initially randomised to treatment were followed up for 24 weeks. RESULTS: The conversion rate for this trial was high (1.6:1), while attrition was 13%. After 24 weeks, there was no significant difference between those randomised to the treatment arm compared with those randomised to the waiting-list control arm on the primary outcome measure, the Hamilton Rating Scale for Anxiety. CONCLUSIONS: Trials of psychological therapies with this population are feasible. Larger definitive trials are now needed. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.
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11. Magnusson C, Lundberg M, Lee BK, Rai D, Karlsson H, Gardner R, Kosidou K, Arver S, Dalman C. {{Maternal vitamin D deficiency and the risk of autism spectrum disorders: population-based study}}. {BJPsych Open};2016 (Mar);2(2):170-172.
BACKGROUND: Maternal vitamin D deficiency may increase risk of autism spectrum disorder (ASD), but direct evidence is lacking. AIMS: To clarify the relationship between maternal vitamin D deficiency and offspring risk of ASD with and without intellectual disability. METHOD: Using a register-based total population study (N=509 639), we calculated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of ASD with and without intellectual disability in relation to lifetime diagnoses of maternal vitamin D deficiency. Although rare, such deficiency was associated with offspring risk of ASD with, but not without, intellectual disability (aORs 2.51, 95% CI 1.22-5.16 and 1.28, 0.68-2.42). Relationships were stronger in non-immigrant children. CONCLUSIONS: If reflecting associations for prenatal hypovitaminosis, these findings imply gestational vitamin D substitution as a means of ASD prevention. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
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12. Miller LE, Burke JD, Troyb E, Knoch K, Herlihy LE, Fein DA. {{Preschool predictors of school-age academic achievement in autism spectrum disorder}}. {Clin Neuropsychol};2016 (Oct 5):1-22.
OBJECTIVE: Characterization of academic functioning in children with autism spectrum disorder (ASD), particularly predictors of achievement, may have important implications for intervention. The current study aimed to characterize achievement profiles, confirm associations between academic ability and concurrent intellectual and social skills, and explore preschool predictors of school-age academic achievement in a sample of children with ASD. METHOD: Children with ASD (n = 26) were evaluated at the approximate ages of two, four, and ten. Multiple regression was used to predict school-age academic achievement in reading and mathematics from both concurrent (i.e. school-age) and preschool variables. RESULTS: Children with ASD demonstrated a weakness in reading comprehension relative to word reading. There was a smaller difference between mathematics skills; math reasoning was lower than numerical operations, but this did not quite reach trend level significance. Concurrent IQ and social skills were associated with school-age academic achievement across domains. Preschool verbal abilities significantly predicted school-age reading comprehension, above and beyond concurrent IQ, and early motor functioning predicted later math skills. CONCLUSIONS: Specific developmental features of early ASD predict specific aspects of school-age achievement. Early intervention targeting language and motor skills may improve later achievement in this population.
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13. Must A, Eliasziw M, Phillips SM, Curtin C, Kral TV, Segal M, Sherwood NE, Sikich L, Stanish HI, Bandini LG. {{The Effect of Age on the Prevalence of Obesity among US Youth with Autism Spectrum Disorder}}. {Child Obes};2016 (Oct 5)
BACKGROUND: We sought to assess the association between age and the prevalence of obesity among children with and without autism spectrum disorder (ASD) in the 2011-2012 National Survey of Children’s Health. METHODS: Analyses were restricted to 43,777 children, ages 10-17, with valid measures of parent-reported weight, height, and ASD status. Exploratory analyses describe the impact of sex, race/ethnicity, and household income on the relationship between age and obesity in ASD. RESULTS: Although the overall prevalence of obesity among children with ASD was significantly (p < 0.001) higher than among children without ASD (23.1% vs. 14.1%, 95% confidence interval for difference 3.6 to 14.4), child age significantly (p = 0.035) modified this difference. In a multivariable logistic regression analysis, adjusted for sex, race/ethnicity, and household income, the odds of obesity among children with ASD compared with children without ASD increased monotonically from ages 10 to 17 years. This pattern arose due to a consistently high prevalence of obesity among children with ASD and a decline in prevalence with advancing age among children without ASD. These findings were replicated using a propensity score analysis. Exploratory analyses suggested that the age-related change in obesity disparity between children with and without ASD may be further modified by sex, race/ethnicity, and household income. CONCLUSIONS: The patterns of prevalence observed with increasing age among children with and without ASD were unexpected. A better understanding of the etiological and maintenance factors for obesity in youth with ASD is needed to develop interventions tailored to the specific needs of these children. Lien vers le texte intégral (Open Access ou abonnement)
14. Pinto RN, Torquato IM, Collet N, Reichert AP, Souza VLN, Saraiva AM. {{Infantile autism: impact of diagnosis and repercussions in family relationships}}. {Rev Gaucha Enferm};2016 (Oct 03);37(3):e61572.
Objective: To analyse the context in which the diagnosis of autism is revealed and the impact of this revelation on family relationships. Methods: This is a qualitative study with 10 families of autistic children assisted at the Psychosocial Care Centre for Children and Youths in a municipality of Paraiba. Data were collected between July and August 2013 through semi-structured interviews and interpreted using thematic content analysis. Results: The identified Main Unit of Analysis and the respective categories were: the impact of disclosing the diagnosis of autism to the family; characteristics of diagnosis disclosure: the place, time, and the dialogic relationship between the professional and the family; changes in family relationships and the mother’s burden when caring for the autistic child. Conclusions: The health professionals who report autism should better prepare the family to cope with the difficulties of this syndrome and autonomously care for the autistic child.
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15. Poole D, Gowen E, Warren PA, Poliakoff E. {{Brief Report: Which Came First? Exploring Crossmodal Temporal Order Judgements and Their Relationship with Sensory Reactivity in Autism and Neurotypicals}}. {J Autism Dev Disord};2016 (Oct 4)
Previous studies have indicated that visual-auditory temporal acuity is reduced in children with autism spectrum conditions (ASC) in comparison to neurotypicals. In the present study we investigated temporal acuity for all possible bimodal pairings of visual, tactile and auditory information in adults with ASC (n = 18) and a matched control group (n = 18). No group differences in temporal acuity for crossmodal stimuli were observed, suggesting that this may be typical in adults with ASC. However, visual-tactile temporal acuity and bias towards vision when presented with visual-auditory information were both predictors of self-reported sensory reactivity. This suggests that reduced multisensory temporal acuity and/or attention towards vision may contribute to atypical sensory reactivity.
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16. Russell G, Collishaw S, Golding J, Kelly SE, Ford T. {{Changes in diagnosis rates and behavioural traits of autism spectrum disorder over time}}. {BJPsych Open};2015 (Oct);1(2):110-115.
BACKGROUND: The increased proportion of UK children diagnosed with autism spectrum disorder (ASD) has been attributed to improved identification, rather than true increase in incidence. AIM: To explore whether the proportion of children with diagnosis of ASD and/or the proportion with associated behavioural traits had increased over a 10-year period. METHOD: A cross-cohort comparison using regression to compare prevalence of diagnosis and behavioural traits over time. Participants were children aged 7 years assessed in 1998/1999 (n=8139) and 2007/2008 (n=13 831). RESULTS: During 1998/1999, 1.09% (95% CI 0.86-1.37) of children were reported as having ASD diagnosis compared with 1.68% (95% CI 1.42-2.00) in 2007/2008: risk ratio (RR)=1.55 (95% CI 1.17-2.06), P=0.003. The proportion of children in the population with behavioural traits associated with ASD was also larger in the later cohort: RR=1.61 (95% CI 1.35-1.92), P<0.001. Increased odds of diagnosis at the later time point was partially accounted for by adjusting for the increased proportion of children with ASD-type traits. CONCLUSIONS: Increased ASD diagnosis may partially reflect increase in rates of behaviour associated with ASD and/or greater parent/teacher recognition of associated behaviours. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence. Lien vers le texte intégral (Open Access ou abonnement)
17. Tonacci A, Billeci L, Ruta L, Tartarisco G, Pioggia G, Gangemi S. {{A systematic review of the association between allergic asthma and autism}}. {Minerva Pediatr};2016 (Oct 05)
BACKGROUND: Autism Spectrum Disorder represents a burdensome condition in early childhood, with a number of risk factors proposed to explain its pathogenesis, most of which without a reliable scientific basis. Allergic asthma is likely to be one of the possible comorbilities of autism. EVIDENCE ACQUISITION: In this paper, the relationship between autism and allergic asthma was analyzed through a systematic literature review, conducted according to the PRISMA guidelines. The review was performed on PubMed and Science Direct database and covered the period January 1, 2004- July 9, 2016. The search was limited to articles published in peer-reviewed journals. The obtained results were sorted by relevance and the most significant case-control, epidemiological and nationwide-based works associating autism and allergic asthma in humans were selected. EVIDENCE SYNTHESIS: A slight correlation between these conditions has been found in more than a half studies selected, suggesting a possible association between the two diseases. Small sample sizes of some works and some methodological limitations rise uncertainty about this link. CONCLUSIONS: Autism Spectrum Disorder and asthma could be associated conditions, as evidenced by the higher prevalence of asthma in autistic children with respect to typically developed controls, with also a verisimilar biological basis. Despite that, future studies are required to provide more reliable data, also by employing animal models, to better clarify this, still unsure, relationship. Methods for study selection and inclusion criteria were specified in advance and documented in PROSPERO protocol #CRD42014012851.
18. Umbricht D, Del Valle Rubido M, Hollander E, McCracken JT, Shic F, Scahill L, Noeldeke J, Boak L, Khwaja O, Squassante L, Grundschober C, Kletzl H, Fontoura P. {{A Single Dose, Randomized, Controlled Proof-of-Mechanism Study of a Novel Vasopressin 1a Receptor Antagonist (RG7713) in High-Functioning Adults with Autism Spectrum Disorder}}. {Neuropsychopharmacology};2016 (Oct 06)
The core symptoms of Autism Spectrum Disorder (ASD) include impaired social communication, repetitive behaviors and restricted interests. No effective pharmacotherapy for these core deficits exists. Within the domain of social communication, the vasopressin system is implicated in social cognition and social signaling deficits of ASD, and represents a potential therapeutic target. We assessed the effects of a single 20 mg intravenous dose of the arginine vasopressin receptor 1A (V1a) antagonist, RG7713, on exploratory biomarkers (eye-tracking), behavioral and clinical measures of social cognition and communication (affective speech recognition [ASR], reading the mind in the eyes [RMET], olfactory identification, scripted interaction), and safety and tolerability in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 19 high-functioning adult male subjects with DSM-IV Autistic Disorder (age 18-45 years; full scale IQ>70; ABC-Irritability subscale 13). Eye-tracking showed an increase in biological motion orienting preference with RG7713 (ES=0.8, p=0.047), and a non-significant improvement in the composite score (ES=0.2, p=0.29). RG7713 reduced ability to detect lust (ES=-0.8, p=0.03), and fear (ES=-0.7, p=0.07) in ASR. However, when all eight individual emotion subscales were combined into an overall ASR performance score, the reduction was non-significant (ES=-0.1, p=0.59). Thirteen adverse events were reported in 10 subjects; all were of mild (11/13) or moderate (2/13) severity. Although interpretation should be cautious due to multiple comparisons and small sample size, these results provide preliminary evidence from experimental and behavioral biomarkers, that blockade of the V1a receptor may improve social communication in adults with high-functioning ASD. ClinicalTrials.gov identifier: NCT01474278 A Study of RO5028442 in Adult Male High-Functioning Autistic Patients. Available at: http://clinicaltrials.gov/ct2/show/NCT01474278Neuropsychopharmacology accepted article preview online, 06 October 2016. doi:10.1038/npp.2016.232.
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19. Vigod SN, Lunsky Y, Cobigo V, Wilton AS, Somerton S, Seitz DP. {{Morbidity and mortality of women and men with intellectual and developmental disabilities newly initiating antipsychotic drugs}}. {BJPsych Open};2016 (Mar);2(2):188-194.
BACKGROUND: While up to 45% of individuals with intellectual and developmental disabilities (IDD) have a comorbid psychiatric disorder, and antipsychotics are commonly prescribed, gender differences in the safety of antipsychotics have rarely been studied in this population. AIMS: To compare men and women with IDD on medical outcomes after antipsychotic initiation. METHOD: Our population-based study in Ontario, Canada, compared 1457 women and 1951 men with IDD newly initiating antipsychotic medication on risk for diabetes mellitus, hypertension, venous thromboembolism, myocardial infarction, stroke and death, with up to 4 years of follow-up. RESULTS: Women were older and more medically complex at baseline. Women had higher risks for venous thromboembolism (HR 1.72, 95% CI 1.15-2.59) and death (HR 1.46, 95% CI 1.02-2.10) in crude analyses; but only thromboembolism risk was greater for women after covariate adjustment (aHR 1.58, 95% CI 1.05-2.38). CONCLUSIONS: Gender should be considered in decision-making around antipsychotic medications for individuals with IDD. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: (c) The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
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20. Wang X, Mu Y, Sun M, Han J. {{Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin homeostasis}}. {J Mol Cell Biol};2016 (Oct 4)
Homeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photoreceptors. The major fly rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how translation of Rh1 is regulated. Here, we show that adult photoreceptors maintain a constant, abundant quantity of ninaE mRNA, which encodes Rh1. We demonstrate that the Fmr1 protein associates with ninaE mRNA and represses its translation. Further, light exposure triggers a calcium-dependent dephosphorylation of Fmr1, which relieves suppression of Rh1 translation. We demonstrate that the catalytic subunit of PP2A (Mts) mediates light-induced Fmr1 dephosphorylation in a regulatory B subunit of PP2A (CKa)-dependent manner. Finally, we show that blocking light-induced Rh1 translation results in reduced light sensitivity. Our results reveal the molecular mechanism of Rh1 homeostasis and physiological consequence of Rh1 dysregulation.
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21. Zhou Y, Kumari D, Sciascia N, Usdin K. {{CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons}}. {Mol Autism};2016;7:42.
BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5′ untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats.
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22. Zoghbi HY. {{Rett Syndrome and the Ongoing Legacy of Close Clinical Observation}}. {Cell};2016 (Oct 6);167(2):293-297.
This year marks the 50th anniversary of the publication of Andreas Rett’s report on 22 girls who developed a peculiar and devastating neurological disorder that later came to bear his name. On this occasion, we reflect on the progress that has occurred in understanding Rett Syndrome, development of potential treatments, and the ramifications that Rett research has had on the fields of neurobiology and genetics.
