1. Bercum FM, Rodgers KM, Benison AM, Smith ZZ, Taylor J, Kornreich E, Grabenstatter HL, Dudek FE, Barth DS. {{Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model}}. {J Neurosci};2015 (Dec 2);35(48):15894-15902.
Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient.We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5.Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures.We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. SIGNIFICANCE STATEMENT: The comorbidity of human autism and epilepsy has been recognized for decades with little understanding of factors that increase risk. We show that two common human risk factors for autism (maternal stress and terbutaline), only when combined, result in severe ASD-like behavior and epilepsy. The significance of this work is fourfold: (1) combinations of teratogens are required to assess true risk in humans; (2) maternal stress and terbutaline, which are frequently combined in pregnant mothers, may be far more of a risk factor than previously appreciated; (3) astrogliosis may be a common mechanism for this syndrome; and (4) this first animal model of environmentally induced autism/epilepsy permits experimental investigation of cellular mechanisms and intervention strategies.
Lien vers le texte intégral (Open Access ou abonnement)
2. Brown BD, Rais T. {{Autism in the Son of a Woman with Mitochondrial Myopathy and Dysautonomia: A Case Report}}. {Innov Clin Neurosci};2015 (Sep-Oct);12(9-10):29-32.
The relationship between autism spectrum disorders and mitochondrial dysfunction, including mitochondrial myopathies and other mitochondrial diseases, is an area of ongoing research. All autism spectrum disorders are known to be heritable, via genetic and/or epigenetic mechanisms, but specific modes of inheritance are not well characterized. Nevertheless, autism spectrum disorders have been linked to many specific genes associated with mitochondrial function, especially to genes involved in mitochondrial tRNA and the electron transport chain, both particularly vulnerable to point mutations, and clinical research also supports a relationship between the two pathologies. Although only a small minority of patients with autism have a mitochondrial disease, many patients with mitochondrial myopathies have autism spectrum disorder symptoms, and these symptoms may be the presenting symptoms, which presents a diagnostic challenge for clinicians. The authors report the case of a 15-year-old boy with a history of autism spectrum disorder and neurocardiogenic syncope, admitted to the inpatient unit for self-injury, whose young mother, age 35, was discovered to suffer from mitochondrial myopathy, dysautonomia, neurocardiogenic syncope, Ehler-Danlos syndrome, and other uncommon multisystem pathologies likely related to mitochondrial dysfunction. This case illustrates the need for a high index of suspicion for mitochondrial disease in patients with autism, as they have two orders of magnitude greater risk for such diseases than the general population. The literature shows that mitochondrial disease is underdiagnosed in autism spectrum disorder patients and should not be viewed as a « zebra » (i.e., an obscure diagnosis that is made when a more common explanation is more likely).
3. Dieme B, Mavel S, Blasco H, Tripi G, Bonnet-Brilhault F, Malvy J, Bocca C, Andres CR, Nadal-Desbarats L, Emond P. {{Metabolomics Study of Urine in Autism Spectrum Disorders Using a Multiplatform Analytical Methodology}}. {J Proteome Res};2015 (Dec 4);14(12):5273-5282.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with no clinical biomarker. The aims of this study were to characterize a metabolic signature of ASD and to evaluate multiplatform analytical methodologies in order to develop predictive tools for diagnosis and disease follow-up. Urine samples were analyzed using (1)H and (1)H-(13)C NMR-based approaches and LC-HRMS-based approaches (ESI+ and ESI- on HILIC and C18 chromatography columns). Data tables obtained from the six analytical modalities on a training set of 46 urine samples (22 autistic children and 24 controls) were processed by multivariate analysis (orthogonal partial least-squares discriminant analysis, OPLS-DA). The predictions from each of these OPLS-DA models were then evaluated using a prediction set of 16 samples (8 autistic children and 8 controls) and receiver operating characteristic curves. Thereafter, a data fusion block-scaling OPLS-DA model was generated from the 6 best models obtained for each modality. This fused OPLS-DA model showed an enhanced performance (R(2)Y(cum) = 0.88, Q(2)(cum) = 0.75) compared to each analytical modality model, as well as a better predictive capacity (AUC = 0.91, p-value = 0.006). Metabolites that are most significantly different between autistic and control children (p < 0.05) are indoxyl sulfate, N-alpha-acetyl-l-arginine, methyl guanidine, and phenylacetylglutamine. This multimodality approach has the potential to contribute to find robust biomarkers and characterize a metabolic phenotype of the ASD population. Lien vers le texte intégral (Open Access ou abonnement)
4. Gliga T, Smith TJ, Likely N, Charman T, Johnson MH. {{Early Visual Foraging in Relationship to Familial Risk for Autism and Hyperactivity/Inattention}}. {J Atten Disord};2015 (Dec 4)
OBJECTIVE: Information foraging is atypical in both autism spectrum disorders (ASDs) and ADHD; however, while ASD is associated with restricted exploration and preference for sameness, ADHD is characterized by hyperactivity and increased novelty seeking. Here, we ask whether similar biases are present in visual foraging in younger siblings of children with a diagnosis of ASD with or without additional high levels of hyperactivity and inattention. METHOD: Fifty-four low-risk controls (LR) and 50 high-risk siblings (HR) took part in an eye-tracking study at 8 and 14 months and at 3 years of age. RESULTS: At 8 months, siblings of children with ASD and low levels of hyperactivity/inattention (HR/ASD-HI) were more likely to return to previously visited areas in the visual scene than were LR and siblings of children with ASD and high levels of hyperactivity/inattention (HR/ASD+HI). CONCLUSION: We show that visual foraging is atypical in infants at-risk for ASD. We also reveal a paradoxical effect, in that additional family risk for ADHD core symptoms mitigates the effect of ASD risk on visual information foraging.
Lien vers le texte intégral (Open Access ou abonnement)
5. Thomas S, Lycett K, Papadopoulos N, Sciberras E, Rinehart N. {{Exploring Behavioral Sleep Problems in Children With ADHD and Comorbid Autism Spectrum Disorder}}. {J Atten Disord};2015 (Dec 4)
OBJECTIVE: This study (a) compared behavioral sleep problems in children with comorbid ADHD and autism spectrum disorder (ASD) with those with ADHD and (b) examined child/family factors associated with sleep problems. METHOD: Cross-sectional study comparison of 392 children with a confirmed ADHD diagnosis (ADHD+ASD, n=93, ADHD, n=299) recruited from 21 peadiatric practises in Victoria, Australia. Data were collected from parents. Key measures included the Child Sleep Habits Questionnaire (CSHQ). RESULTS: Children with ADHD + ASD experienced similar levels and types of behavioral sleep problems compared with those with ADHD. In both groups, the presence of co-occurring internalizing and externalizing comorbidities was associated with sleep problems. Sleep problems were also associated with parent age in the ADHD + ASD group and poorer parent mental health in the ADHD group. CONCLUSION: Findings suggest comorbid ASD is not associated with increased behavioral sleep problems in children with ADHD and that co-occurring internalizing and externalizing comorbidities may flag children in these groups with sleep problems.
Lien vers le texte intégral (Open Access ou abonnement)
6. Vignoli A, La Briola F, Peron A, Turner K, Vannicola C, Saccani M, Magnaghi E, Scornavacca GF, Canevini MP. {{Autism spectrum disorder in tuberous sclerosis complex: searching for risk markers}}. {Orphanet J Rare Dis};2015;10:154.
BACKGROUND: Neuropsychiatric disorders are present in up to 90% of patients with Tuberous Sclerosis Complex (TSC), and represent an important issue for families. Autism Spectrum Disorder (ASD) is the most common neurobehavioral disease, affecting up to 61% of patients. The aims of this study were: 1) to assess the prevalence of ASD in a TSC population; 2) to describe the severity of ASD; 3) to identify potential risk factors associated with the development of ASD in TSC patients. METHODS: We selected 42 individuals over age 4 years with a definite diagnosis of TSC and followed at a TSC clinic in Northern Italy. We collected and reported clinical and genetic data, as well as cognitive level, for each of them. We administered the Social Communication Questionnaire (SCQ) as a reliable screening tool for ASD, and performed comparisons between the average scores and each clinical and genetic feature. RESULTS: Seventeen out of 42 patients (40.5%) had a score at the SCQ suggestive of ASD (>/=15 points). When calculated for each cognitive level category, the average SCQ score tended to be progressively higher in patients with a worse cognitive level, and the number of pathological SCQ scores increased with worsening of intellectual disability. With respect to ASD severity, the scores were equally distributed, indicating that the degree of ASD in TSC patients may have a large variability. By comparing the average SCQ scores with the clinical features, we found statistically significant correlations with epilepsy, seizure onset before age one year, spasms, mutations in TSC2, cognitive level, sleep disorders, and other psychiatric problems, but not with seizure frequency, tubers localization and gender. CONCLUSIONS: Our study showed a prevalence of ASD of 40.5%, confirming the higher risk for this disorder in patients with TSC. However, the severity seems to have a notable variability in TSC patients. Risk factors for ASD are epilepsy, infantile spams, and mutations in TSC2.
Lien vers le texte intégral (Open Access ou abonnement)
7. Yarlagadda A, Acharya G, Kasaraneni J, Hampe CS, Clayton AH. {{Placental Barrier and Autism Spectrum Disorders: The Role of Prolactin and Dopamine on the Developing Fetal Brain}}. {Innov Clin Neurosci};2015 (Sep-Oct);12(9-10):14-17.
Dopamine and prolactin exhibit opposite effects on lactation. However, a possible role for increased prolactin/dopamine ratio in postpartum mood and thought disorders and as a prognostic indicator of the mother’s future mental health has not been well investigated. Postpartum depression is a serious condition with potentially devastating outcomes for both the mother and the infant. Early detection and treatment of this condition can have impressive results. Treatment options include antidepressant medications for mood disorders and use of antipsychotics and electroconvulsive therapy to address postpartum psychosis. Although there are obvious benefits of such treatments on the welfare of the mother and her child, broader implications of these treatments on lactation and child growth and development are not known. This review article explores a possible link between in-utero exposure to a high maternal prolactin/dopamine ratio and subsequent development of autism spectrum disorders. We hypothesize that a comprehensive, biologically oriented approach to the use of psychotropics in the regulation of neurotransmission during pre- and postpartum periods may result in better outcomes in this population.
8. Zablotsky B, Black LI, Maenner MJ, Schieve LA, Blumberg SJ. {{Estimated Prevalence of Autism and Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey}}. {Natl Health Stat Report};2015 (Nov)(87):1-21.
The developmental disabilities questions in the 2014 National Health Interview Survey (NHIS) were changed from previous years, including question reordering and a new approach to asking about autism spectrum disorder (ASD). This report examines survey-based estimates of the lifetime prevalence of ASD, intellectual disability (ID), and any other developmental delay (other DD) following the inclusion of a standalone ASD question, the inclusion of specific diagnoses in the ASD question, and the ASD question preceding the other DD question, and compares them with estimates from previous years.
