1. Goldman SE, Alder ML, Burgess HJ, Corbett BA, Hundley R, Wofford D, Fawkes DB, Wang L, Laudenslager ML, Malow BA. {{Characterizing Sleep in Adolescents and Adults with Autism Spectrum Disorders}}. {J Autism Dev Disord};2017 (Mar 12)
We studied 28 adolescents/young adults with autism spectrum disorders (ASD) and 13 age/sex matched individuals of typical development (TD). Structured sleep histories, validated questionnaires, actigraphy (4 weeks), and salivary cortisol and melatonin (4 days each) were collected. Compared to those with TD, adolescents/young adults with ASD had longer sleep latencies and more difficulty going to bed and falling asleep. Morning cortisol, evening cortisol, and the morning-evening difference in cortisol did not differ by diagnosis (ASD vs. TD). Dim light melatonin onsets (DLMOs) averaged across participants were not different for the ASD and TD participants. Average participant scores indicated aspects of poor sleep hygiene in both groups. Insomnia in ASD is multifactorial and not solely related to physiological factors.
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2. Li D, Karnath HO, Xu X. {{Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies}}. {Neurosci Bull};2017 (Apr);33(2):219-237.
Searching for effective biomarkers is one of the most challenging tasks in the research field of Autism Spectrum Disorder (ASD). Magnetic resonance imaging (MRI) provides a non-invasive and powerful tool for investigating changes in the structure, function, maturation, connectivity, and metabolism of the brain of children with ASD. Here, we review the more recent MRI studies in young children with ASD, aiming to provide candidate biomarkers for the diagnosis of childhood ASD. The review covers structural imaging methods, diffusion tensor imaging, resting-state functional MRI, and magnetic resonance spectroscopy. Future advances in neuroimaging techniques, as well as cross-disciplinary studies and large-scale collaborations will be needed for an integrated approach linking neuroimaging, genetics, and phenotypic data to allow the discovery of new, effective biomarkers.
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3. Liu S, Zhou L, Yuan H, Vieira M, Sanz-Clemente A, Badger JD, 2nd, Lu W, Traynelis SF, Roche KW. {{A rare variant identified within the GluN2B C-terminus in a patient with autism affects NMDA receptor surface expression and spine density}}. {J Neurosci};2017 (Mar 10)
NMDA receptors (NMDARs) are ionotropic glutamate receptors that are crucial for neuronal development and higher cognitive processes. NMDAR dysfunction is involved in a variety of neurological and psychiatric diseases; however, the mechanistic link between the human pathology and NMDAR dysfunction is poorly understood. Rare missense variants within NMDAR subunits have been identified in numerous patients with mental or neurological disorders. We specifically focused on the GluN2B NMDAR subunit, which is highly expressed in the hippocampus and cortex throughout development. We analyzed several variants located in the GluN2B C-terminus, and found that 3 variants in patients with autism (S1415L) or schizophrenia (L1424F and S1452F) (S1413L, L1422F, S1450F in rodents, respectively) displayed impaired binding to MAGUK proteins. In addition, we observed a deficit in surface expression for GluN2B S1413L. Furthermore, there were fewer dendritic spines in GluN2B S1413L-expressing neurons. Importantly, synaptic NMDAR currents in neurons transfected with GluN2B S1413L in GluN2A/B deficient mouse brain slices revealed only partial rescue of synaptic current amplitude. Functional properties of GluN2B S1413L in recombinant systems revealed no change in receptor properties, consistent with synaptic defects being the result of reduced trafficking and targeting of GluN2B S1413L to the synapse. Thus, we find that GluN2B S1413L displays deficits in NMDAR trafficking, synaptic currents, and spine density, raising the possibility that this mutation may contribute to the phenotype in this autism patient. More broadly, our research demonstrates that the targeted study of certain residues in NMDARs based on rare variants identified in patients is a powerful approach to study receptor function.SIGNIFICANCE STATEMENTWe have used a bedside to bench approach to investigate the functional regulation of NMDA receptors (NMDARs). Using information from deep sequencing of patients with neurological or psychiatric disorders, we investigated missense variants identified in the intracellular C-terminal domain of the GluN2B NMDAR subunit. We found several variants that displayed altered properties. In particular, one variant identified in a patient with autism, human GluN2B S1415L, displayed reduced surface expression and binding to PSD-95. Furthermore expression of GluN2B S1415L (S1413L in mouse) showed a deficit in rescue of synaptic NMDAR currents and fewer dendritic spines, consistent with other reports of spine abnormalities being associated with autism. More broadly, we demonstrate that using patient data is an effective approach to probe the structure/function relationship of NMDARs.
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4. Lortie M, Proulx-Begin L, Saint-Amour D, Cousineau D, Theoret H, Lepage JF. {{Brief Report: Biological Sound Processing in Children with Autistic Spectrum Disorder}}. {J Autism Dev Disord};2017 (Mar 10)
There is debate whether social impairments in autism spectrum disorder (ASD) are truly domain-specific, or if they reflect generalized deficits in lower-level cognitive processes. To solve this issue, we used auditory-evoked EEG responses to assess novelty detection (MMN component) and involuntary attentional orientation (P3 component) induced by socially-relevant, human-produced, biological sounds and acoustically-matched control stimuli in children with ASD and controls. Results show that early sensory and novelty processing of biological stimuli are preserved in ASD, but that automatic attentional orientation for biological sounds is markedly altered. These results support the notion that at least some cognitive processes of ASD are specifically altered when it comes to processing social stimuli.
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5. Moskowitz LJ, Walsh CE, Mulder E, McLaughlin DM, Hajcak G, Carr EG, Zarcone JR. {{Intervention for Anxiety and Problem Behavior in Children with Autism Spectrum Disorder and Intellectual Disability}}. {J Autism Dev Disord};2017 (Mar 11)
There is little research on the functional assessment and treatment of anxiety and related problem behavior in children with autism spectrum disorder (ASD), particularly those with intellectual and developmental disability (IDD). In a recent study, we evaluated a multimethod strategy for assessing anxiety in children with ASD and IDD (Am J Intellect Dev Disabil 118:419-434, 2013). In the present study, we developed treatments for the anxiety and associated problem behavior in these same children. A multiple baseline design was used to evaluate the effectiveness of a multicomponent intervention package, incorporating individualized strategies from Positive Behavior Support and Cognitive Behavioral Therapy. During intervention, all three participants showed substantial decreases in anxiety and problem behavior and significant increases in respiratory sinus arrhythmia in the situations that had previously been identified as anxiety-provoking.
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6. Robert C, Pasquier L, Cohen D, Fradin M, Canitano R, Damaj L, Odent S, Tordjman S. {{Role of Genetics in the Etiology of Autistic Spectrum Disorder: Towards a Hierarchical Diagnostic Strategy}}. {Int J Mol Sci};2017 (Mar 12);18(3)
Progress in epidemiological, molecular and clinical genetics with the development of new techniques has improved knowledge on genetic syndromes associated with autism spectrum disorder (ASD). The objective of this article is to show the diversity of genetic disorders associated with ASD (based on an extensive review of single-gene disorders, copy number variants, and other chromosomal disorders), and consequently to propose a hierarchical diagnostic strategy with a stepwise evaluation, helping general practitioners/pediatricians and child psychiatrists to collaborate with geneticists and neuropediatricians, in order to search for genetic disorders associated with ASD. The first step is a clinical investigation involving: (i) a child psychiatric and psychological evaluation confirming autism diagnosis from different observational sources and assessing autism severity; (ii) a neuropediatric evaluation examining neurological symptoms and developmental milestones; and (iii) a genetic evaluation searching for dysmorphic features and malformations. The second step involves laboratory and if necessary neuroimaging and EEG studies oriented by clinical results based on clinical genetic and neuropediatric examinations. The identification of genetic disorders associated with ASD has practical implications for diagnostic strategies, early detection or prevention of co-morbidity, specific treatment and follow up, and genetic counseling.
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7. Wen Z, Cheng TL, Yin DZ, Sun SB, Wang Z, Yu SY, Zhang Y, Qiu Z, Du YS. {{Identification of the Genetic Cause for Childhood Disintegrative Disorder by Whole-Exome Sequencing}}. {Neurosci Bull};2017 (Apr);33(2):251-254.
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8. Zhang R, Zhang HF, Han JS, Han SP. {{Genes Related to Oxytocin and Arginine-Vasopressin Pathways: Associations with Autism Spectrum Disorders}}. {Neurosci Bull};2017 (Apr);33(2):238-246.
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorders characterized by impaired social interactions, communication deficits, and repetitive behavior. Although the mechanisms underlying its etiology and manifestations are poorly understood, several lines of evidence from rodent and human studies suggest involvement of the evolutionarily highly-conserved oxytocin (OXT) and arginine-vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behavior. As far as we know, there is no comprehensive review of the roles of the OXT and AVP systems in the development of ASD from the genetic aspect. In this review, we summarize the current knowledge regarding associations between ASD and single-nucleotide variants of the human OXT-AVP pathway genes OXT, AVP, AVP receptor 1a (AVPR1a), OXT receptor (OXTR), the oxytocinase/vasopressinase (LNPEP), and ADP-ribosyl cyclase (CD38).
