1. Bakker-Huvenaars MJ, Greven CU, Herpers P, Wiegers E, Jansen A, van der Steen R, van Herwaarden AE, Baanders AN, Nijhof KS, Scheepers F, Rommelse N, Glennon JC, Buitelaar JK. {{Saliva oxytocin, cortisol, and testosterone levels in adolescent boys with autism spectrum disorder, oppositional defiant disorder/conduct disorder and typically developing individuals}}. {Eur Neuropsychopharmacol};2018 (Sep 7)
The aim of the current study was to compare levels of oxytocin, cortisol, and testosterone in adolescents with either autism spectrum disorder (ASD), or oppositional defiant disorder (ODD)/conduct disorder (CD), and in typically developing individuals (TDI), and relate hormone levels to severity and subtype of aggression and callous-unemotional (CU) traits. Saliva concentrations of oxytocin, cortisol, and testosterone were assessed in 114 male participants (N=49 ASD, N=37 ODD/CD, N=28 TDI,) aged 12-19 years (M=15.4 years, SD=1.9). The ASD and the ODD/CD groups had significantly lower levels of oxytocin than the TDI group, and the ODD/CD group had significantly higher levels of testosterone than the ASD group. There were no group effects on cortisol levels. Group differences remained for oxytocin after correcting for the influence of CU traits, but were not significant after controlling for aggression. Results for testosterone became non-significant after correction for either CU traits or aggression. Across groups, higher levels of CU traits were related to higher levels of cortisol and testosterone, however, proactive and reactive aggression were unrelated to all three hormonal levels. The current findings show that, regardless of cognitive ability or comorbid disorders, the diagnostic groups (ASD, ODD/CD) differ from each other by their hormonal levels, with the ASD group characterized by relative low level of oxytocin, and the ODD/CD group by a relative low level of oxytocin and high level of testosterone. These group effects were partly driven by differences in CU traits between the groups.
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2. Caffarelli C, Francolini V, Hayek J, Valacchi G, Giannotti S, Nuti R, Gonnelli S. {{Bone status in relation to ambulatory performance in girls with Rett syndrome: a 10-year longitudinal study}}. {Pediatr Res};2018 (Aug 9)
BACKGROUND: Low bone mass is a frequent and early complication of girls with Rett syndrome. As a consequence of the low bone mass, Rett patients are at an increased risk of fragility fractures. This study aimed to investigate the long-term influences of mobility on bone status in girls with Rett syndrome. METHODS: In 58 girls with Rett syndrome, biochemical parameters and quantitative ultrasound parameters at phalanges (amplitude-dependent speed of sound: AD-SoS and bone transmission time: BTT) were measured at baseline and after 5 and 10 years. The subjects were divided into two groups: nonambulatory (n = 28) and ambulatory (n = 30). RESULTS: In nonambulatory Rett subjects, the values of AD-SoS and BTT were significantly lower than in ambulatory Rett subjects at each time point. However, during the 10-year follow-up both ambulatory and nonambulatory Rett patients showed a similar worsening in their bone status. CONCLUSION: This longitudinal study suggests that both ambulatory and nonambulatory Rett subjects present a progressive deterioration of bone status as assessed by quantitative ultrasound parameters, and the ambulatory impairment and the nutritional status seem to play a key role in the deterioration of bone status.
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3. Ghirardi L, Pettersson E, Taylor MJ, Freitag CM, Franke B, Asherson P, Larsson H, Kuja-Halkola R. {{Genetic and environmental contribution to the overlap between ADHD and ASD trait dimensions in young adults: a twin study}}. {Psychol Med};2018 (Sep 7):1-9.
BACKGROUND: Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults. METHODS: We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components. RESULTS: At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43). CONCLUSIONS: We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.
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4. Hou Q, Wang Y, Li Y, Chen D, Yang F, Wang S. {{A Developmental Study of Abnormal Behaviors and Altered GABAergic Signaling in the VPA-Treated Rat Model of Autism}}. {Front Behav Neurosci};2018;12:182.
Although studies have investigated the role of gamma-aminobutyric acid (GABA)ergic signaling in rodent neural development and behaviors relevant to autism, behavioral ontogeny, as underlain by the changes in GABAergic system, is poorly characterized in different brain regions. Here, we employed a valproic acid (VPA) rat model of autism to investigate the autism-like behaviors and GABAergic glutamic acid decarboxylase 67 (GAD67) expression underlying these altered behaviors in multiple brain areas at different developmental stages from birth to adulthood. We found that VPA-treated rats exhibited behavioral abnormalities relevant to autism, including delayed nervous reflex development, altered motor coordination, delayed sensory development, autistic-like and anxiety behaviors and impaired spatial learning and memory. We also found that VPA rats had the decreased expression of GAD67 in the hippocampus (HC) and cerebellum from childhood to adulthood, while decreased GAD67 expression of the temporal cortex (TC) was only observed in adulthood. Conversely, GAD67 expression was increased in the prefrontal cortex (PFC) from adolescence to adulthood. The dysregulated GAD67 expression could alter the excitatory-inhibitory balance in the cerebral cortex, HC and cerebellum. Our findings indicate an impaired GABAergic system could be a major etiological factor occurring in the cerebral cortex, HC and cerebellum of human cases of autism, which suggests enhancement of GABA signaling would be a promising therapeutic target for its treatment.
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5. Iritani S, Torii Y, Habuchi C, Sekiguchi H, Fujishiro H, Yoshida M, Go Y, Iriki A, Isoda M, Ozaki N. {{The neuropathological investigation of the brain in a monkey model of autism spectrum disorder with ABCA13 deletion}}. {Int J Dev Neurosci};2018 (Sep 7);71:130-139.
The precise biological etiology of autism spectrum disorder (ASD) remains unknown. In this study, we investigated the neuropathology of a monkey model of autism Human ABCA13 is the largest ABC transporter protein, with a length of 5058 amino acids and a predicted molecular weight of >450 kDa. However, the function of this protein remains to be elucidated. This protein is thought to be associated with major psychiatric disease. Using this monkey model of autism with an ABCA13 deletion and a mutation of 5HT2c, we neuropathologically investigated the changes in the neuronal formation in the frontal cortex. As a result, the neuronal formation in the cortex was found to be disorganized with regard to the neuronal size and laminal distribution in the ABCA13 deletion monkey. The catecholaminergic and GABAergic neuronal systems, serotoninergic neuronal formation (5HT2c) were also found to be impaired by an immunohistochemical evaluation. This study suggested that ABCA13 deficit induces the impairment of neuronal maturation or migration, and the function of the neuronal network. This protein might thus play a role in the neurodevelopmental function of the central nervous system and the dysfunction of this protein may be a pathophysiological cause of mental disorders including autism.
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6. Kupeli I, Tepe E, Kuyrukluyildiz U. {{Use of sugammadex in Rett syndrome: A case report}}. {J Dent Anesth Pain Med};2018 (Aug);18(4):261-265.
Rett syndrome (RS) is a neurodevelopmental disorder characterized by loss of cognitive, motor, and social skills, epilepsy, autistic behavior, abnormal airway patterns, gastroesophageal reflux, nutritional problems, and severe scoliosis. Although girls with RS show normal or near-normal growth until 6-8 months, they lose their skills after that. The anesthetic management of these patients requires care because of all these clinical features. Especially in the postoperative period, prolonged apnea is common and extubation is delayed. In this case report, the effect of using sugammadex was presented in a 16-year-old girl with RS. The patient’s all bimaxillary teeth and 4 wisdom teeth were extracted under general anesthesia in one session with minimal surgical trauma and moderate bleeding. Sugammadex can be a rapid and reliable agent for the reversal of the neuromuscular block in neurodegenerative patients.
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7. Masiran R. {{Autism and trichotillomania in an adolescent boy}}. {BMJ Case Rep};2018 (Sep 5);2018
An adolescent with autism spectrum disorder and improperly treated attention deficit hyperactivity disorder presented with recurrent hair pulling. Treatment with selective serotonin reuptake inhibitor and stimulant improved these conditions.
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8. Miyajima A, Tateyama K, Fuji S, Nakaoka K, Hirao K, Higaki K. {{Development of an Intervention Programme for Selective Eating in Children with Autism Spectrum Disorder}}. {Hong Kong J Occup Ther};2017 (Dec);30(1):22-32.
Objective/Background: Most parents of children with autism spectrum disorder (ASD) have difficulties with the selective eating behaviour of their children. This study aimed to develop a newly designed intervention programme on improving selective eating behaviour for parents of children with ASD and evaluate its effectiveness. Methods: The participants were 23 parents of children (aged 3-6 years) with ASD. The education programme included a session that addressed approaches to improve selective eating and attitudes at meal times, with a discussion. The intervention aimed to identify the underlying factors and approaches to improve selective eating in children and the self-efficacy of parents. Results: Significant differences were observed before and after the intervention in the degree of difficulty perceived by parents, their degree of self-efficacy, the number of recommendations conducted by them, their subjective view of the degree of dietary imbalance, and the number of food items consumed by their children. Conclusion: We developed an interventional programme for parents of children with ASD and this programme was found to be useful. It is important for occupational therapists to consider the factors and approaches for selective eating in children with ASD in order to provide early intervention for their parents.
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9. Napoli E, Schneider A, Wang JY, Trivedi A, Carrillo NR, Tassone F, Rogawski M, Hagerman RJ, Giulivi C. {{Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study}}. {Mol Neurobiol};2018 (Sep 5)
Currently, there is no effective treatment for the fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. In this pilot study, we evaluated whether allopregnanolone, a natural neurosteroid that exerts beneficial effects in neurodegenerative diseases, nervous system injury, and peripheral neuropathies, could improve lymphocytic bioenergetics and plasma pharmacometabolomics in six males with FXTAS (68 +/- 3 years old; FMR1 CGG repeats 94 +/- 4; FXTAS stages ranging from 3 to 5) enrolled in a 12-week open-label intervention study conducted at the University of California Davis from December 2015 through July 2016. Plasma pharmacometabolomics and lymphocytic mitochondria function were assessed at baseline (on the day of the first infusion) and at follow-up (within 48 h from the last infusion). In parallel, quantitative measurements of tremor and ataxia and neuropsychological evaluations of mental state, executive function, learning, memory, and psychological symptoms were assessed at the same time points. Allopregnanolone treatment impacted significantly GABA metabolism, oxidative stress, and some of the mitochondria-related outcomes. Notably, the magnitude of the individual metabolic response, as well as the correlation with some of the behavioral tests, was overwhelmingly carrier-specific. Based on this pilot study, allopregnanolone treatment has the potential for improving cognitive and GABA metabolism in FXTAS aligned with the concept of precision medicine.
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10. Narzisi A, Posada M, Barbieri F, Chericoni N, Ciuffolini D, Pinzino M, Romano R, Scattoni ML, Tancredi R, Calderoni S, Muratori F. {{Prevalence of Autism Spectrum Disorder in a large Italian catchment area: a school-based population study within the ASDEU project}}. {Epidemiol Psychiatr Sci};2018 (Sep 6):1-10.
AimsThis study aims to estimate Autism Spectrum Disorders (ASD) prevalence in school-aged children in the province of Pisa (Italy) using the strategy of the ASD in the European Union (ASDEU) project. METHODS: A multistage approach was used to identify cases in a community sample (N = 10 138) of 7-9-year-old children attending elementary schools in Pisa – Italy. First, the number of children with a disability certificate was collected from the Local Health Authority and an ASD diagnosis was verified by the ASDEU team. Second, a Teacher Nomination form (TN) to identify children at risk for ASD was filled in by teachers who joined the study and the Social Communication Questionnaire (SCQ) was filled in by the parents of children identified as positive by the TN; a comprehensive assessment, which included the Autism Diagnostic Observation Schedule-Second Edition, was performed for children with positive TN and SCQ9. RESULTS: A total of 81 children who had a disability certificate also had ASD (prevalence: 0.79%, i.e. 1/126). Specifically, 66 children (57 males and nine females; 62% with intellectual disability -ID-) were certified with ASD, whereas another 15 (11 males and four females; 80% with ID) were recognised as having ASD among those certified with another neurodevelopmental disorder. Considering the population of 4417 (children belonging to schools which agreed to participate in the TN/SCQ procedure) and using only the number of children certified with ASD, the prevalence (38 in 4417) was 0.86%, i.e. one in 116. As far as this population is concerned, the prevalence rises to 1% if we consider the eight new cases (six males and two females; no subject had ID) identified among children with no pre-existing diagnoses and to 1.15%, i.e., one in 87, if probabilistic estimation is used. CONCLUSIONS: This is the first population-based ASD prevalence study conducted in Italy so far and its results indicate a prevalence of ASD in children aged 7-9 years of about one in 87. This finding may help regional, national and international health planners to improve ASD policies for ASD children and their families in the public healthcare system.
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11. Patusco R, Ziegler J. {{Role of Probiotics in Managing Gastrointestinal Dysfunction in Children with Autism Spectrum Disorder: An Update for Practitioners}}. {Adv Nutr};2018 (Sep 7)
Children with autism spectrum disorder (ASD) are 4 times as likely to experience gastrointestinal symptoms as children without ASD. The gut microbiota has increasingly been the subject of investigation as a contributing factor to these symptoms in this population because there is evidence to suggest that alterations in the intestinal microflora are correlated with gastrointestinal and ASD symptom severity. Probiotic therapy has been proposed as a treatment for augmented gastrointestinal symptom severity in children with ASD. This narrative review systematically searched the literature to provide an update for practitioners on the state of the evidence surrounding probiotic therapy in children with ASD as a treatment option for reducing gastrointestinal symptoms. A total of 186 articles were screened and 5 articles met the inclusion criteria. A collective sample of 117 children with ASD is represented and outcomes addressed include improvement in gastrointestinal symptoms as well as influence of probiotic supplementation on the gut microbiota and ASD symptoms and behavior. There is promising evidence to suggest that probiotic therapy may improve gastrointestinal dysfunction, beneficially alter fecal microbiota, and reduce the severity of ASD symptoms in children with ASD. Future research is still warranted in this area because there are methodologic flaws in the available literature and optimal species, strains, dosages, and duration of treatment have not been identified.
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12. Trobiani L, Favaloro FL, Di Castro MA, Di Mattia M, Cariello M, Miranda E, Canterini S, De Stefano ME, Comoletti D, Limatola C, De Jaco A. {{UPR activation specifically modulates glutamate neurotransmission in the cerebellum of a mouse model of autism}}. {Neurobiol Dis};2018 (Sep 7);120:139-150.
An increasing number of rare mutations linked to autism spectrum disorders have been reported in genes encoding for proteins involved in synapse formation and maintenance, such as the post-synaptic cell adhesion proteins neuroligins. Most of the autism-linked mutations in the neuroligin genes map on the extracellular protein domain. The autism-linked substitution R451C in Neuroligin3 (NLGN3) induces a local misfolding of the extracellular domain, causing defective trafficking and retention of the mutant protein in the endoplasmic reticulum (ER). The activation of the unfolded protein response (UPR), due to misfolded proteins accumulating in the ER, has been implicated in pathological and physiological conditions of the nervous system. It was previously shown that the over-expression of R451C NLGN3 in a cellular system leads to the activation of the UPR. Here, we have investigated whether this protective cellular response is detectable in the knock-in mouse model of autism endogenously expressing R451C NLGN3. Our data showed up-regulation of UPR markers uniquely in the cerebellum of the R451C mice compared to WT littermates, at both embryonic and adult stages, but not in other brain regions. Miniature excitatory currents in the Purkinje cells of the R451C mice showed higher frequency than in the WT, which was rescued inhibiting the PERK branch of UPR. Taken together, our data indicate that the R451C mutation in neuroligin3 elicits UPR in vivo, which appears to trigger alterations of synaptic function in the cerebellum of a mouse model expressing the R451C autism-linked mutation.
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13. Wachspress B, Maeir A, Mazor-Karsenty T. {{Content Validity of the Parentship Protocol: A Multidimensional Intervention for Parents of Adolescents with High-Functioning Autism Spectrum Disorder}}. {Phys Occup Ther Pediatr};2018 (Sep 6):1-15.
The Parentship protocol is a short-term intervention program in occupational therapy for parents of adolescents with High-Functioning Autism Spectrum Disorder (HFASD). Its purpose is to promote parental resilience and enhance adolescents’ participation in daily life. AIMS: To explore and analyze the perceptions of occupational therapists and parents of individuals with HFASD, regarding the content of the protocol and its theoretical framework. METHODS: Implementation of a phenomenological qualitative approach using two focus groups (six occupational therapists and five parents). A transcript-based analysis was used for analyzing the data. RESULTS: The degree of agreement regarding the potential purposes and contents of the protocol was high. In addition, nine themes were raised and led to changes and additions in the protocol. CONCLUSIONS: The study provided support for content validity and acceptability of the Parentship protocol. Future research should test the feasibility of this new intervention program.
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14. Willem L, Knops N, Mekahli D, Cochat P, Edefonti A, Verrina E, Groothoff J, Lagae L, Pirenne J, Dobbels F, Borry P, Van Geet C, Levtchenko E. {{Renal Replacement Therapy in children with severe developmental disability: guiding questions for decision-making}}. {Eur J Pediatr};2018 (Sep 7)
Whether to initiate or to withhold Renal Replacement Therapy (RRT) in children with severe developmental disability (DD) remains a topic of intense debate. The present study investigated the opinion of professionals on this difficult issue and proposed a checklist with guiding questions for decision-making. Clinicians affiliated to different organizations involved in pediatric nephrology worldwide were invited to respond to a web-based survey. This survey focused on the collection of demographic data of the respondents together with their opinion concerning the decision-making regarding RRT in a particular case and for children with severe DD in general. A total of 286 professionals responded to the survey. Sixty-six percent supported initiating RRT in the child of the case report, with pre-emptive transplantation being the preferred modality. Important arguments pro RRT initiation in children with severe DD in general were parental preference, decrease of suffering, and improvement of survival and quality of life. Important contraindications included low IQ, severe comorbidities, and inability of the patient to take medication or for the family to provide sufficient care. CONCLUSION: The present study presents an inventory on the opinions of health care professionals involved in RRT in children regarding the treatment of children with DD and assists in the decision-making process by identifying important medical and psychosocial arguments for initiating or withholding RRT in severe DD patients. What is Known: *Renal Replacement Therapy (RRT) in children with severe developmental disability (DD) is a topic of intense debate. *Previous studies on the opinion of professionals mainly focused on the use of IQ as an argument in the decision-making whether or not starting RRT. What is New: *The present study investigated the opinion of professionals with regard to considering initiation or withholding RRT in children with severe DD and identified medical and psychosocial arguments playing a role in the decision-making process. *Based on these arguments, a checklist with guiding questions for decision-making is proposed.
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15. Zhang D, Poustka L, Marschik PB, Einspieler C. {{The onset of hand stereotypies in fragile X syndrome}}. {Dev Med Child Neurol};2018 (Oct);60(10):1060-1061.
