1. Hashemi E, Ariza J, Lechpammer M, Noctor SC, Martinez-Cerdeno V. {{Abnormal white matter tracts resembling pencil fibers involving prefrontal cortex (Brodmann area 47) in autism: a case report}}. {J Med Case Rep}. 2016; 10(1): 237.
BACKGROUND: Autism is not correlated with any neuropathological hallmark as the brain of autistic individuals lack defined lesions. However, previous investigations have reported cortical heterotopias and local distortion of the cytoarchitecture of the neocortex in some cases of autism. CASE PRESENTATION: Our patient was a 40-year-old white woman diagnosed at an early age with autism and mental retardation. Pencil fibers were present within the prefrontal cortex (Brodmann area 47) and its composition resembled that of the underlying white matter region. Pencil fibers encompassed most of the extent of the cortical grey matter and were populated by oligodendrocytes, astrocytes, and microglial cells, but not by neurons. CONCLUSIONS: Here we report a new cytoarchitectural abnormality that has not been previously described in autism. Future pathological examinations should keep in mind the potential presence of pencil fibers within the prefrontal cortex of cases with autism.
Lien vers le texte intégral (Open Access ou abonnement)
2. Liu CX, Peng XL, Hu CC, Li CY, Li Q, Xu X. {{Developmental profiling of ASD-related shank3 transcripts and their differential regulation by valproic acid in zebrafish}}. {Dev Genes Evol}. 2016.
SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood. Here, we investigated temporal, spatial, and isoform-specific expression patterns of shank3 during zebrafish development on the basis of previous researches and the differential effects of each shank3 transcript expression after exposure to valproic acid (VPA), an ASD-associated drug. At first, we observed that both shank3a and shank3b were barely expressed at very early ages (before 24 h post-fertilization (hpf)), whereas their expression levels were increased and mainly enriched in the nervous system after 24 hpf. Secondly, all of the six shank3 transcripts gradually increased during the first 7 hpf and then decreased. Subsequently, they exhibited a second increasing peak between 1 month post-fertilization (mpf) and adulthood. Thirdly, VPA treatment affected the isoform-specific expression of zebrafish shank3. In particular, the mRNA expression levels of those isoforms that contain a SAM domain were significantly increased, whereas the mRNA expression level of those which contained an ANK domain but without a SAM domain was decreased. To conclude, our findings support the molecular diversity of shank3 in zebrafish and provide a molecular framework to understand the isoform-specific function of shank3 in zebrafish.
Lien vers le texte intégral (Open Access ou abonnement)
3. Niemczyk J, von Gontard A, Equit M, Bauer K, Naumann T, Wagner C, Curfs L. {{Detailed assessment of incontinence in boys with fragile-X-syndrome in a home setting}}. {Eur J Pediatr}. 2016.
Fragile-X-syndrome (FXS) is caused by a mutation on the X chromosome (Xq27.3). Males with a full mutation have typical dysmorphic signs, moderate intellectual disability and psychological disorders. Twenty-five to fifty percent are affected by incontinence. The aim of the study was to assess subtypes of incontinence and psychological problems in children with FXS in their home environments. Twenty-two boys with FXS (mean age 11.0 years) and 22 healthy controls (mean age 11.1 years) were examined with sonography, uroflowmetry, 48-h bladder diary, physical examination, IQ test, parental psychiatric interview and questionnaires regarding incontinence and psychological symptoms in a home setting. Boys with FXS had higher rates of incontinence than controls (59.1 vs. 4.8 %). The most common subtypes in FXS boys were primary non-monosymptomatic nocturnal enuresis, urge incontinence and nonretentive faecal incontinence. 90.9 % boys with FXS had a psychological comorbidity. Incontinence and behavioural symptoms were not associated. CONCLUSION: Boys with FXS have a higher risk for physical disabilities, psychological disorders and incontinence than healthy boys. Constipation is not a major problem in FXS. As effective treatment is available for children with ID, we recommend offering assessment and therapy to all children with FXS and incontinence. WHAT IS KNOWN: * Boys with fragile-X-syndrome (FXS) have higher rates of incontinence, psychological disorders and somatic conditions than typically developing boys. What is New: * Constipation is a rare condition in FXS in contrast to other genetic syndromes. * Although incontinence rates are higher, urological findings (uroflowmetry, sonography) are not more pathological per se in FXS.
Lien vers le texte intégral (Open Access ou abonnement)
4. Pecora LA, Mesibov GB, Stokes MA. {{Sexuality in High-Functioning Autism: A Systematic Review and Meta-analysis}}. {J Autism Dev Disord}. 2016.
Preliminary research examining sexuality within High-Functioning Autism (HFA) has been yet to consider the impact sex may have on the sexual/romantic functioning of this population. A systematic database search was carried out to identify 27 observational and cross-sectional publications meeting predetermined inclusion criteria. Using standardised mean differences, a random-effects meta-analysis pooled data from 9 eligible studies. Exhibiting higher levels of sexual understanding, females with HFA were subject to more adverse sexual experiences than males with HFA and neurotypical counterparts. Males reported greater desire for, and engagement in both solitary and dyadic sexual contact. Findings have provided initial insight into characterising the sexuality of males and females with HFA, yet also necessitated the need for future research in the field.
Lien vers le texte intégral (Open Access ou abonnement)
5. Porokhovnik LN, Kostyuk SV, Ershova ES, Stukalov SM, Veiko NN, Korovina NY, Gorbachevskaya NL, Sorokin AB, Lyapunova NA. {{[The maternal effect in infantile autism: elevated DNA damage degree in patients and their mothers]}}. {Biomed Khim}. 2016; 62(4): 466-70.
Infantile autism is a common disorder of mental development, which is characterized by impairments in the communicative, cognitive and speech spheres and obsessional stereotyped behaviour. Although in most cases, pathogenic factors remain unclear, infantile autism has a significant hereditary component, however, its etiology is also under the influence of environmental factors, including the condition of the mother’s body during pregnancy (« maternal effect »). Oxidative stress is assumed to play a key role in the pathogenesis of infantile autism. It is known that oxidative stress has a prominent genotoxic effect, which is realized through inducing single and double strand breaks of the nuclear DNA. We evaluated the degree of DNA damage in patients with infantile autism and their mothers using DNA comet assay. The comet tail moment and DNA per cent ratio in the tail were assessed for each individual. The two parameters appeared to be strongly correlated (r=0.90). Mean and median values of both parameters were considerably higher in the sample of autistic children, than in age-matching healthy controls. Interestingly, these parameters were also elevated in healthy mothers of autistic children, with no difference from the values in the group of autistic children. The control group of healthy women of reproductive age, who had no children with autism, differed by the DNA comet tail moment from the group of mothers of autistic children, but did not differ significantly from the control group of healthy children. The results suggest that there are genotoxic factors in mentally healthy mothers of autistic children, which can determine the pathological process in the foeti via environmental « maternal effect » during gestation.
Lien vers le texte intégral (Open Access ou abonnement)
6. Riikonen R. {{Treatment of autistic spectrum disorder with insulin-like growth factors}}. {Eur J Paediatr Neurol}. 2016.
There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism-based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity-dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD-like behavior defects. The molecular basis for a cerebellar contribution has been demonstrated in a mouse model. These have led to a potential mechanism-based use of drug targets and mouse models. Neurotrophic factors are potential candidates for the treatment. Insulin-like growth factor-1 (IGF-1) is altered in autism. It reduces neuro-inflammation: by causing changes of cytokines such as IL-6 and microglial function. IGF-1 reduces the defects in the synapse. It alleviates NMDA-induced neurotoxicity via the IGF-AKT-mTor pathway in microglia. IGF-1 may rescue function in Rett syndrome and ASD caused by changes of the SCHANK3 gene. There are recently pilot studies of the treatment of Rett syndrome and of SCHANK3 gene deficiency syndromes. The FDA has granted Orphan drug designations for Fragile X syndrome, SCHANK3 gene deficiency syndrome and Rett syndrome.
Lien vers le texte intégral (Open Access ou abonnement)
7. Schwichtenberg AJ, Hensle T, Honaker S, Miller M, Ozonoff S, Anders T. {{Sibling sleep-What can it tell us about parental sleep reports in the context of autism?}}. {Clin Pract Pediatr Psychol}. 2016; 4(2): 137-52.
Sleep problems are common in families raising children with Autism Spectrum Disorder (ASD). Clinicians often depend on parent reports of child sleep but minimal research exists to address the accuracy or biases in these reports. To isolate parent-report accuracy (from differences in sleep behaviors), the sleep of younger siblings were assessed within a two-group design. The present study compared parent diary reports of infant sibling sleep to videosomnography and actigraphy. In the high-risk group, families had at least one child with ASD and a younger sibling (n = 33). The low-risk comparison group had no family history of ASD (n = 42). We confirmed comparable sleep behaviors between the groups and used paired t tests, two-one-sided-tests (TOST), and Bland-Altman plots to assess parent report accuracy. The parameters of sleep onset, nighttime sleep duration, awakenings, morning rise time, and daytime sleep duration were evaluated. Diary and videosomnography estimates were comparable for nighttime sleep duration, morning rise time, and awakenings for both groups. Diary and actigraph estimates were less comparable for both groups. Daytime sleep duration estimates had the largest discrepancy with both groups reporting (on average) 40 additional minutes of sleep when compared to actigraphy estimates. In the present study, families raising children with ASD were just as accurate as other families when reporting infant sleep behaviors. Our findings have direct clinical implications and support the use of parent nighttime sleep reports.
Lien vers le texte intégral (Open Access ou abonnement)
8. Welsh JP, Oristaglio JT. {{Autism and Classical Eyeblink Conditioning: Performance Changes of the Conditioned Response Related to Autism Spectrum Disorder Diagnosis}}. {Front Psychiatry}. 2016; 7: 137.
Changes in the timing performance of conditioned responses (CRs) acquired during trace and delay eyeblink conditioning (EBC) are presented for diagnostic subgroups of children having autism spectrum disorder (ASD) aged 6-15 years. Children diagnosed with autistic disorder (AD) were analyzed separately from children diagnosed with either Asperger’s syndrome or Pervasive developmental disorder (Asp/PDD) not otherwise specified and compared to an age- and IQ-matched group of children who were typically developing (TD). Within-subject and between-groups contrasts in CR performance on sequential exposure to trace and delay EBC were analyzed to determine whether any differences would expose underlying functional heterogeneities of the cerebral and cerebellar systems, in ASD subgroups. The EBC parameters measured were percentage CRs, CR onset latency, and CR peak latency. Neither AD nor Asp/PDD groups were impaired in CR acquisition during trace or delay EBC. Both AD and Asp/PDD altered CR timing, but not always in the same way. Although the AD group showed normal CR timing during trace EBC, the Asp/PDD group showed a significant 27 and 28 ms increase in CR onset and peak latency, respectively, during trace EBC. In contrast, the direction of the timing change was opposite during delay EBC, during which the Asp/PDD group showed a significant 29 ms decrease in CR onset latency and the AD group showed a larger 77 ms decrease in CR onset latency. Only the AD group showed a decrease in CR peak latency during delay EBC, demonstrating another difference between AD and Asp/PDD. The difference in CR onset latency during delay EBC for both AD and Asp/PDD was due to an abnormal prevalence of early onset CRs that were intermixed with CRs having normal timing, as observed both in CR onset histograms and mean CR waveforms. In conclusion, significant heterogeneity in EBC performance was apparent between diagnostic groups, and this may indicate that EBC performance can report the heterogeneity in the neurobiological predispositions for ASD. The findings will inform further explorations with larger cohorts, different sensory modalities, and different EBC paradigms and provide a reference set for future EBC studies of children having ASD and non-human models.
Lien vers le texte intégral (Open Access ou abonnement)
9. Zheng Z, Warren Z, Weitlauf A, Fu Q, Zhao H, Swanson A, Sarkar N. {{Brief Report: Evaluation of an Intelligent Learning Environment for Young Children with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
Researchers are increasingly attempting to develop and apply innovative technological platforms for early detection and intervention of autism spectrum disorder (ASD). This pilot study designed and evaluated a novel technologically-mediated intelligent learning environment with relevance to early social orienting skills. The environment was endowed with the capacity to administer social orienting cues and adaptively respond to autonomous real-time measurement of performance (i.e., non-contact gaze measurement). We evaluated the system with both toddlers with ASD (n = 8) as well as typically developing infants (n = 8). Children in both groups were able to ultimately respond accurately to social prompts delivered by the technological system. Results also indicated that the system was capable of attracting and pushing toward correct performance autonomously without user intervention.
