1. Cattane N, Richetto J, Cattaneoa A. {{Prenatal exposure to environmental insults and enhanced risk of developing Schizophrenia and Autism Spectrum Disorder: Focus on biological pathways and epigenetic mechanisms}}. {Neurosci Biobehav Rev}. 2018.
When considering neurodevelopmental disorders (NDDs), Schizophrenia (SZ) and Autism Spectrum Disorder (ASD) are considered to be among the most severe in term of prevalence, morbidity and impact on the society. Similar features and overlapping symptoms have been observed at multiple levels, suggesting common pathophysiological bases. Indeed, recent genome-wide association studies (GWAS) and epidemiological data report shared vulnerability genes and environmental triggers across the two disorders. In this review, we will discuss the possible biological mechanisms, including glutamatergic and GABAergic neurotransmissions, inflammatory signals and oxidative stress related systems, which are targeted by adverse environmental exposures and that have been associated with the development of SZ and ASD. We will also discuss the emerging role of the gut microbiome as possible interplay between environment, immune system and brain development. Finally, we will describe the involvement of epigenetic mechanisms in the maintenance of long-lasting effects of adverse environments early in life. This will allow us to better understand the pathophysiology of these NDDs, and also to identify novel targets for future treatment strategies.
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2. Dickerson AS, Dickerson AS. {{Brief Report: Texas School District Autism Prevalence in Children from Non-English-Speaking Homes}}. {J Autism Dev Disord}. 2018.
Previous studies have implicated migration and ethnicity as possible risk factors for autism spectrum disorder (ASD) in developed countries. Using Texas education data, we calculated district-reported ASD prevalence stratified by geographic region, with reported home language as a proxy for immigration. Prevalence ratios were also stratified by race. Prevalence estimates were significantly lower for White children from homes speaking Spanish and other non-English languages compared to those from English-speaking homes. This is the first study, to our knowledge, that investigates ASD prevalence of children from non-English-speaking households in a large sample. Barriers in identification of children of immigrants with ASD indicate that the increased district-reported prevalence seen in our study may only be a small indicator of a potentially larger prevalence.
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3. Henriksen MW, Breck H, von Tetzchner S, Paus B, Skjeldal OH, Brodtkorb E. {{Epilepsy in classic Rett syndrome: Course and characteristics in adult age}}. {Epilepsy research}. 2018; 145: 134-9.
PURPOSE: Rett syndrome (RTT) is a neurodevelopmental disorder that almost exclusively affects females. Epilepsy is a major clinical feature, but its long-term course in RTT has not been sufficiently explored. This study addresses the development of the epilepsy in adults with RTT. METHODS: Available females diagnosed with RTT in Norway were asked to participate. Parents/caregivers were interviewed, the girls/women were examined and their medical records reviewed. Participants were categorized according to age, epilepsy, seizure patterns and mutation severity groups. RTT severity was assessed (epilepsy score excluded). RESULTS: 70 females with classic RTT were included. A presumed pathogenic mutation in MECP2 was found in 96%. The presence of active epilepsy (seizures last five years) was similar in all age groups above the age of ten: 11 (65%) in adolescents (11-20 years), 9 (60%) in young adults (21-30 years) and 14 (67%) in participants above 30 years of age. Tonic-clonic seizures within the last year were present in 55, 67 and 64%, and>/=weekly seizures occurred in 27, 45 and 50% in the respective age groups. Among participants with active epilepsy, 69% had unremitting seizures, whereas 31% had experienced remissions for more than six months during the last five years. In the oldest group (>30 years), only 19% had obtained seizure control for >5 years, and 14% had never experienced seizures. Seizure activity correlated with RTT severity score, whereas the relationship to mutation type remained ambiguous. CONCLUSION: Epilepsy continues to be a major concern in adults with RTT. Two thirds of women above 30 years of age remained with active epilepsy and 50% of them had seizures at least weekly.
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4. Karjalainen L, Rastam M, Paulson-Karlsson G, Wentz E. {{Do autism spectrum disorder and anorexia nervosa have some eating disturbances in common?}}. {Eur Child Adolesc Psychiatry}. 2018.
A possible overlap between autism spectrum disorder (ASD) and anorexia nervosa (AN), in terms of both behavioural and cognitive features, has led to new areas of research. The aim of the present study was to examine the occurrence of eating behaviours frequently seen in ASD among adolescents and young adults with AN. The participants were females within the age range 15-25 years: 36 with current AN (32 were followed up after 1 year), 19 with ASD, and 30 healthy females. The participants completed the SWedish Eating Assessment for Autism spectrum disorders (SWEAA) and the Autism Spectrum Quotient tool (AQ). AN groups had significantly higher SWEAA scores than the healthy comparison group, also when patients had gained weight. Typical autistic eating behaviours, such as selective eating, were more common in the AN groups than in the ASD group. This is the first time that SWEAA has been implemented in an AN population. Eating behaviours frequently seen in ASD seem to be frequent in AN and some remain also after weight gain.
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5. Khalaj R, Hajizadeh Moghaddam A, Zare M. {{Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism}}. {Int J Dev Neurosci}. 2018; 69: 80-7.
Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the comparative effects of hesperetin (Hst) and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were VPA-exposed which received hesperetin and nano-hesperetin (10 and 20mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high level of anxiety-like behaviors (P< 0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido-inflammatory markers. Hesperetin and nano-hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p< 0.05) plasma's inflammation indexes. In conclusion, it can be state that nano-hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation. Lien vers le texte intégral (Open Access ou abonnement)
6. Knox J, Arpadi SM, Kauchali S, Craib M, Kvalsvig JD, Taylor M, Bah F, Mellins C, Davidson LL. {{Screening for developmental disabilities in HIV positive and HIV negative children in South Africa: Results from the Asenze Study}}. {PLoS One}. 2018; 13(7): e0199860.
BACKGROUND: While neurodevelopmental abnormalities are common in children with HIV infection, their detection can be challenging in settings with limited availability of health professionals. The aim of this study was to assess the ability to identify developmental disability among HIV positive and HIV negative children living in South Africa with an internationally used screen. METHODS AND FINDINGS: This analysis uses a sample of 1,330 4-6 year old children and 1,231 of their caregivers in KwaZulu-Natal, South Africa, including administration of the Ten Questions (TQ) screen, a standardized medical history and physical examination conducted by a medical doctor, with hearing and vision screening, psychological assessment for cognition and language delay, and voluntary HIV testing. There was a high prevalence of disability among the sample. Compared to HIV negative children, HIV positive children were more likely to screen positive on at least one TQ item (59.3 vs 42.8%, p = 0.01), be delayed in sitting, standing or walking (OR 3.89, 95% CI = 2.1-7.2) and have difficulty walking or weakness in the arms or legs (OR = 2.7, 95%CI = 0.8-9.37). By medical doctor assessment, HIV positive children were more likely to be diagnosed with gross motor disability (OR = 3.5, 95%CI = 1.3-9.2) and hearing disability (OR = 2.5, 95%CI = 1.2-5.3). By independent psychological assessment, HIV positive children were more likely to have cognitive delay (OR = 2.2, 95%CI = 1.2-3.9) and language delay (OR = 4.3, 95%CI = 2.2-8.4). Among HIV positive children, the sensitivity and specificity of the TQ for serious disability (vs. no disability) was 100% and 51.2%, respectively. Among HIV-negative children, the sensitivity and specificity of the TQ for serious disability (vs. no disability) was 90.2% and 63.9%, respectively. CONCLUSIONS: In this first report of the use of the TQ screen in the isiZulu language, it was found to have high sensitivity for detecting serious developmental disabilities in children, especially HIV positive children. The performance of the TQ in this sample indicates utility for making best use of limited neurodevelopmental resources by screening HIV positive children.
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7. La Buissonniere-Ariza V, Wood JJ, Kendall PC, McBride NM, Cepeda SL, Small BJ, Lewin AB, Kerns C, Storch EA. {{Presentation and Correlates of Hoarding Behaviors in Children with Autism Spectrum Disorders and Comorbid Anxiety or Obsessive-Compulsive Symptoms}}. {J Autism Dev Disord}. 2018.
We investigated the presentation and correlates of hoarding behaviors in 204 children aged 7-13 with autism spectrum disorder (ASD) and comorbid anxiety or obsessive-compulsive disorder (OCD) symptoms. Approximately 34% of the sample presented at least moderate levels, and with 7% presenting severe to extreme levels of hoarding. Child gender predicted hoarding severity. In addition, child ASD-related social difficulties together with attention-deficit and hyperactivity disorder symptom severity positively predicted hoarding controlling for child gender and restricted and repetitive behaviors. Finally, child anxiety/OCD symptoms positively predicted hoarding, controlling for all other factors. These results suggest hoarding behaviors may constitute a common feature of pediatric ASD with comorbid anxiety/OCD, particularly in girls and children with greater social difficulties and comorbid psychiatric symptom severity.
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8. Lammert CR, Frost EL, Bolte AC, Paysour MJ, Shaw ME, Bellinger CE, Weigel TK, Zunder ER, Lukens JR. {{Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism}}. {Journal of immunology (Baltimore, Md : 1950)}. 2018; 201(3): 845-50.
Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome-immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood. In this study, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a murine maternal immune activation (MIA) model of autism that is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that preconception microbiota transplantation can transfer susceptibility to MIA-associated neurodevelopmental disease and that this is associated with modulation of the maternal immune response. Furthermore, we find that ablation of IL-17a signaling provides protection against the development of neurodevelopmental abnormalities in MIA offspring. Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.
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9. Lumaka A, Lubala TK, Race V, Peeters H, Lukusa P, Devriendt K. {{Usefulness of fragile X checklist and CGG distribution in specialized institutions in Kinshasa, DR Congo}}. {Journal of community genetics}. 2018.
Screening for fragile X syndrome (FXS) is essential in children with developmental delay or intellectual disability (ID). In addition, using clinical screening checklists remains of high interest in resource-limited settings. We aimed to gain insight into the prevalence of FXS and the distribution of CGG alleles and to evaluate the usefulness of three checklists in specialized institutions in Kinshasa, DR Congo. We recruited 80 males and 25 females from six specialized institutions in Kinshasa and administered a questionnaire comprising items from the following FXS checklists: Hagerman, Maes, and Guruju. FMR1 CGG repeats were assessed for every patient. About 37% of patients were referable for FX testing based on Hagerman’s checklist, 35% for Maes’, and 43.80% for Guruju’s, but none of them was molecularly confirmed to have FXS. Thus, specificities were 62.86, 64.76, and 56.5%, respectively, for Hagerman, Maes, and Guruju, respectively. The mean CGG allele size was 28.55 +/- 2.83 (ranges, 17-48). The 29 CGG was the most frequent allele (24.61%). Thus, existing checklists should not be automatically applied to Congolese patients without adjustments. The distribution of CGG repeats and the number of CGG alleles are similar to other African studies.
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10. Mastrominico A, Fuchs T, Manders E, Steffinger L, Hirjak D, Sieber M, Thomas E, Holzinger A, Konrad A, Bopp N, Koch SC. {{Effects of Dance Movement Therapy on Adult Patients with Autism Spectrum Disorder: A Randomized Controlled Trial}}. {Behav Sci (Basel)}. 2018; 8(7).
This study examines the effects of dance movement therapy (DMT) on empathy for adults with autism spectrum disorder (ASD). DMT based on the embodiment approach offers body-centered interventions, such as mirroring techniques, to address the needs of ASD patients. Accordingly, findings of a feasibility study suggest that DMT may be an effective approach for clients on the ASD spectrum. The present study is a randomized controlled trial that was conducted as a multicenter study within the framework of the EU-funded research project TESIS (Toward an Embodied Science of Intersubjectivity), and employed a two-factorial between-subject design. The treatment group (n = 35) participated in a 10-week manualized DMT intervention, whereas the control group (n = 22) received treatment only after a waiting period. Empathy, measured with the Cognitive and Emotional Empathy Questionnaire (CEEQ), was the main variable of interest, analyzed by a repeated measures analysis of variance. In order to also include incomplete data cases, we used the expectation-maximization algorithm for missing data estimation. Results suggest no significant changes in overall empathy between groups. We discuss the results and limitations, as well as future research options.
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11. Melancia F, Schiavi S, Servadio M, Cartocci V, Campolongo P, Palmery M, Pallottini V, Trezza V. {{Sex specific autistic endophenotypes induced by prenatal exposure to valproic acid involve anandamide signaling}}. {British journal of pharmacology}. 2018.
BACKGROUND AND PURPOSE: Autism spectrum disorder (ASD) is more commonly diagnosed in males than in females. Prenatal exposure to the antiepileptic drug valproic acid (VPA) is an environmental risk factor of ASD. Male rats prenatally exposed to VPA show socio-emotional autistic-like dysfunctions that have been related with changes in the activity of the endocannabinoid anandamide. Our aim was to investigate whether prenatal VPA induces sex specific autistic endophenotypes involving anandamide signaling. EXPERIMENTAL APPROACH: We studied sex-specific differences in the ASD-like socio-emotional, cognitive and repetitive symptoms displayed in the course of development by rats prenatally exposed to VPA, and investigated the role of anandamide in the autistic-like symptoms displayed by VPA-exposed rats of both sexes. KEY RESULTS: Female rats were less vulnerable to the deleterious effects of prenatal VPA exposure on social communication, emotional reactivity and cognitive performance than male rats. Conversely, similarly to what happens in male rats, prenatal VPA exposure induced selective deficits in social play behavior and stereotypies in the female rat offspring. At the neurochemical level, prenatal VPA exposure altered the phosphorylation of CB1 cannabinoid receptors in a sex-, age- and tissue-specific manner. Enhancing anandamide signaling through inhibition of its degradation reversed the behavioral deficits displayed by VPA-exposed animals of both sexes. CONCLUSION AND IMPLICATION: These findings highlight sexually-dimorphic consequences of prenatal VPA exposure that may be related to a sex-specific impact of VPA on endocannabinoid neurotransmission in the course of development, and introduce a new therapeutic target for reversing autistic-like symptoms in both sexes.
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12. Mensi MM, Gasparini L, Chiappedi M, Guerini FR, Orlandi M, Rogantini C, Balottin U. {{Empathy and behavior in children affected by Autism Spectrum Disorders}}. {Minerva pediatrica}. 2018.
BACKGROUND: Many studies have already shown that individuals suffering from Autism Spectrum Disorders (ASD) present low levels of empathy: in fact, reduced emotional reciprocity is considered a clinically significant indicator of autistic functioning. We decided to investigate the role of empathy in determining pathological behaviors in children affected by ASD considering parents’ point of view and to evaluate the presence of differences between mothers and fathers’ perception of their child’s empathy and behaviors. METHODS: We compared empathy levels in a sample of 58 patients with ASD as reported by a parent-filled questionnaire with the results of a global evaluation conducted by means of play observations, clinician-rated scales, a semi-structured interview with both caregivers and parent-filled questionnaires. RESULTS: The majority of ASD patients have low levels of empathy according to both parents’ points of view; noteworthy, mothers and fathers are highly concordant in this respect. Children’s levels of empathy negatively correlate with many behavioral problems, both internalizing and externalizing. Furthermore, we found that mothers tend to perceive more internalizing problems, while fathers are more willing to notice externalizing ones. CONCLUSIONS: Involving both caregivers in children’s diagnostic assessment could deepen patient’s evaluation and finally the therapeutic results. Mothers and fathers seem to be highly consistent in describing the psychological characteristics of their child, but not in respect to symptoms.
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13. Morrison-Levy N, Go C, Ochi A, Otsubo H, Drake J, Rutka J, Weiss SK. {{Children with autism spectrum disorders and drug-resistant epilepsy can benefit from epilepsy surgery}}. {Epilepsy Behav}. 2018; 85: 200-4.
OBJECTIVE: The objective of this research was to evaluate a cohort of children with both autism spectrum disorder (ASD) and drug-resistant epilepsy (DRE) after epilepsy surgery to determine predictors of best outcome. METHODS: Retrospective chart review was done for 29 children ages 2 to 18years with ASD and DRE who had neurosurgical intervention for seizure management over 15years at one institution. All subjects had at least 1year of follow-up. Data abstraction included demographic information, seizure diagnosis, treatment, investigations, surgical intervention, neuropsychological assessment, and outcome. Statistical analysis software (SAS) was used for statistical analysis. Engel classification was used to assess seizure outcome. RESULTS: Fifteen subjects had resective surgery. Fourteen had palliative surgery with vagal nerve stimulator (VNS) insertion (13) and corpus callosotomy (1). Of the 29 subjects, 35% had class I outcome (all in the resective group). When combining all subjects (resective and palliative), 66% of subjects benefited with class I-III outcomes. In the total cohort, age at time of surgery was significant, with class I outcome more frequently seen in the younger age group when compared with classes II-IV (p=0.01). CONCLUSION: A subset of children with ASD can benefit from resective surgery, and for those who are not candidates, a VNS can offer significant improvements in seizure control.
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14. Sanchez-Sanchez SM, Magdalon J, Griesi-Oliveira K, Yamamoto G, Santacruz-Perez C, Fogo M, Passos-Bueno MR, Sertie AL. {{Rare RELN variants affect Reelin-DAB1 signal transduction in autism spectrum disorder}}. {Human mutation}. 2018.
The Reelin-DAB1 signaling pathway plays a crucial role in regulating neuronal migration and synapse function. While many rare heterozygous variants in the Reelin gene (RELN) have been identified in patients with autism spectrum disorder (ASD), most variants are still of unknown clinical significance. Also, genetic data suggest that heterozygous variants in RELN alone appear to be insufficient to cause ASD. Here, we describe the identification and functional characterization of rare compound heterozygous missense variants in RELN in a patient with ASD in whom we have previously reported hyperfunctional mTORC1 signaling of yet unknown etiology. Using iPSC-derived neural progenitor cells (NPCs) from this patient, we provide experimental evidence that the identified variants are deleterious and lead to diminished Reelin secretion and impaired Reelin-DAB1 signal transduction. Also, our results suggest that mTORC1 pathway overactivation may function as a second hit event contributing to downregulation of the Reelin-DAB1 cascade in patient-derived NPCs, and that inhibition of mTORC1 by rapamycin attenuates Reelin-DAB1 signaling impairment. Taken together, our findings point to an abnormal interplay between Reelin-DAB1 and mTORC1 networks in nonsyndromic ASD. This article is protected by copyright. All rights reserved.
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15. Zuckerman KE, Chavez AE, Murillo CR, Lindly OJ, Reeder JA. {{Disparities in Familiarity with Developmental Disabilities among Low-Income Parents}}. {Academic pediatrics}. 2018.
OBJECTIVE: Parent knowledge about developmental disabilities (DDs) may facilitate access to DD care; however, parents may vary in their knowledge and familiarity with common DDs. This study aimed to assess racial/ethnic and language differences in low-income families’ familiarity, knowledge, and personal experience with DDs. METHODS: We conducted a child development survey among 539 low-income parents of young children attending visits at the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), in six Oregon counties in 2015. Survey items assessed parent familiarity with early signs of DDs, self-reported knowledge about DDs, and personal experience with a friend or family member with a DD. Bivariable and multivariable analyses assessed differences in outcomes among non-Latino white [white], Latino-English proficient [Latino-EP], Latino-limited English proficient [Latino-LEP], and non-Latino other race English proficient [other race] parents. RESULTS: Overall, parent participants correctly identified 64.7% of early signs of DDs. White parents correctly identified the earliest signs, even after adjustment for socio-demographic factors. Latino-LEP, Latino-EP and other race parents were less likely to have heard of prevalent DDs such as ADHD and autism, and were less likely to have a friend or family member with a DD compared to white parents. CONCLUSIONS: Low-income Latino-LEP and other race parents have less familiarity or personal experience with DDs, and are less aware of DD early signs compared to low-income white parents. Study findings suggest that interventions to reduce disparities in DD diagnosis and treatment should include increasing information transfer to parents in racial/ethnic and language minority communities. WHAT’S NEW: Low-income racial/ethnic minority parents, and particularly Latinos parents with limited English proficiency, have less familiarity or personal experience with DDs, and are less aware of DD early signs compared to low-income white parents.
