1. Bourgeron T. {{From the genetic architecture to synaptic plasticity in autism spectrum disorder}}. {Nature reviews Neuroscience}. 2015 Aug 20;16(9):551-63.
Genetics studies of autism spectrum disorder (ASD) have identified several risk genes that are key regulators of synaptic plasticity. Indeed, many of the risk genes that have been linked to these disorders encode synaptic scaffolding proteins, receptors, cell adhesion molecules or proteins that are involved in chromatin remodelling, transcription, protein synthesis or degradation, or actin cytoskeleton dynamics. Changes in any of these proteins can increase or decrease synaptic strength or number and, ultimately, neuronal connectivity in the brain. In addition, when deleterious mutations occur, inefficient genetic buffering and impaired synaptic homeostasis may increase an individual’s risk for ASD.
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2. Carr T, Shih W, Lawton K, Lord C, King B, Kasari C. {{The relationship between treatment attendance, adherence, and outcome in a caregiver-mediated intervention for low-resourced families of young children with autism spectrum disorder}}. {Autism}. 2015 Aug 19.
Rates of participation in intervention research have not been extensively studied within autism spectrum disorder. Such research is important given the benefit of early intervention on long-term prognosis for children with autism spectrum disorder. The goals of this study were to examine how family demographic factors predicted treatment attendance and adherence in a caregiver-mediated randomized controlled trial targeting core deficits of autism spectrum disorder, and whether treatment attendance and adherence predicted outcome. In all, 147 caregiver-child dyads from a low-resourced population were randomized to in-home caregiver-mediated module or group-based caregiver education module treatment. Treatment attendance, adherence, and outcome (time spent in joint engagement) were the primary outcome variables. The majority of families who entered treatment (N = 87) maintained good attendance. Attendance was significantly predicted by socioeconomic status, site, and treatment condition. Families in caregiver-mediated module reported lower levels of treatment adherence, which was significantly predicted by site, condition, caregiver stress, and child nonverbal intelligence quotient. Dyads in caregiver-mediated module had significantly longer interactions of joint engagement, which was significantly predicted by an interaction between treatment attendance and condition. Overall, the results from this study stress the importance of considering demographic variables in research design when considering barriers to treatment attendance and adherence.
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3. Contractor A, Klyachko VA, Portera-Cailliau C. {{Altered Neuronal and Circuit Excitability in Fragile X Syndrome}}. {Neuron}. 2015 Aug 19;87(4):699-715.
Fragile X syndrome (FXS) results from a genetic mutation in a single gene yet produces a phenotypically complex disorder with a range of neurological and psychiatric problems. Efforts to decipher how perturbations in signaling pathways lead to the myriad alterations in synaptic and cellular functions have provided insights into the molecular underpinnings of this disorder. From this large body of data, the theme of circuit hyperexcitability has emerged as a potential explanation for many of the neurological and psychiatric symptoms in FXS. The mechanisms for hyperexcitability range from alterations in the expression or activity of ion channels to changes in neurotransmitters and receptors. Contributions of these processes are often brain region and cell type specific, resulting in complex effects on circuit function that manifest as altered excitability. Here, we review the current state of knowledge of the molecular, synaptic, and circuit-level mechanisms underlying hyperexcitability and their contributions to the FXS phenotypes.
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4. Durieux AM, Horder J, Mendez MA, Egerton A, Williams SC, Wilson CE, Spain D, Murphy C, Robertson D, Barker GJ, Murphy DG, McAlonan GM. {{Cortical and subcortical glutathione levels in adults with autism spectrum disorder}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Aug 20.
Increased oxidative stress has been postulated to contribute to the pathogenesis of autism spectrum disorder (ASD). However, reports of alterations in oxidation markers including glutathione (GSH), the major endogenous antioxidant, are indirect, coming from blood plasma level measurements and postmortem studies. Therefore we used in-vivo 3 Tesla proton magnetic resonance spectroscopy ([1H]MRS) to directly measure GSH concentrations in the basal ganglia (BG) and the dorsomedial prefrontal cortex of 21 normally intelligent adult males with ASD and 29 controls who did not differ in age or IQ. There was no difference in brain GSH between patients and controls in either brain area; neither did GSH levels correlate with measures of clinical severity in patients. Thus [1H]MRS measures of cortical and subcortical GSH are not a biomarker for ASD in intellectually able adult men. Autism Res 2015. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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5. Green RR, Bigler ED, Froehlich A, Prigge MB, Travers BG, Cariello AN, Anderson JS, Zielinski BA, Alexander A, Lange N, Lainhart JE. {{Beery VMI performance in autism spectrum disorder}}. {Child neuropsychology : a journal on normal and abnormal development in childhood and adolescence}. 2015 Aug 21:1-23.
Few studies have examined the visuomotor integration (VMI) abilities of individuals with autism spectrum disorder (ASD). An all-male sample consisting of 56 ASD participants (ages 3-23 years) and 36 typically developing (TD) participants (ages 4-26 years) completed the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) as part of a larger neuropsychological battery. Participants were also administered standardized measures of intellectual functioning and the Social Responsiveness Scale (SRS), which assesses autism and autism-like traits. The ASD group performed significantly lower on the Beery VMI and on all IQ measures compared to the TD group. VMI performance was significantly correlated with full scale IQ (FSIQ), performance IQ (PIQ), and verbal IQ (VIQ) in the TD group only. However, when FSIQ was taken into account, no significant Beery VMI differences between groups were observed. Only one TD participant scored 1.5 standard deviations (SDs) below the Beery VMI normative sample mean, in comparison to 21% of the ASD sample. As expected, the ASD group was rated as having significantly higher levels of social impairment on the SRS compared to the TD group across all major domains. However, level of functioning on the SRS was not associated with Berry VMI performance. These findings demonstrate that a substantial number of individuals with ASD experience difficulties compared to TD in performing VMI-related tasks, and that VMI is likely affected by general cognitive ability. The fact that lowered Beery VMI performance occurred only within a subset of individuals with ASD and did not correlate with SRS would indicate that visuomotor deficits are not a core feature of ASD, even though they present at a higher rate of impairment than observed in TD participants.
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6. Nelson SB, Valakh V. {{Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders}}. {Neuron}. 2015 Aug 19;87(4):684-98.
Autism spectrum disorders (ASDs) and related neurological disorders are associated with mutations in many genes affecting the ratio between neuronal excitation and inhibition. However, understanding the impact of these mutations on network activity is complicated by the plasticity of these networks, making it difficult in many cases to separate initial deficits from homeostatic compensation. Here we explore the contrasting evidence for primary defects in inhibition or excitation in ASDs and attempt to integrate the findings in terms of the brain’s ability to maintain functional homeostasis.
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7. Ngounou Wetie AG, Wormwood KL, Charette L, Ryan JP, Woods AG, Darie CC. {{Comparative two-dimensional polyacrylamide gel electrophoresis of the salivary proteome of children with autism spectrum disorder}}. {Journal of cellular and molecular medicine}. 2015 Aug 20.
In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two-dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change >/=1.7 and a P-value <0.05 or a fold change of >/=3.0 between ASD cases and controls were analysed by nanoLC-MS/MS. Alpha-amylase, CREB-binding protein, p532, Transferrin, Zn alpha2 glycoprotein, Zymogen granule protein 16, cystatin D and plasminogen were down-regulated in ASD. Increased expression of proto-oncogene Frequently rearranged in advanced T-cell lymphomas 1 (FRAT1), Kinesin family member 14, Integrin alpha6 subunit, growth hormone regulated TBC protein 1, parotid secretory protein, Prolactin-inducible protein precursor, Mucin-16, Ca binding protein migration inhibitory factor-related protein 14 (MRP14) was observed in individuals with ASD. Many of the identified proteins have previously been linked to ASD or were proposed as risk factors of ASD at the genetic level. Some others are involved in pathological pathways implicated in ASD causality such as oxidative stress, lipid and cholesterol metabolism, immune system disturbances and inflammation. These data could contribute to protein signatures for ASD presence, risk and subtypes, and advance understanding of ASD cause as well as provide novel treatment targets for ASD.
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8. Palmer RF, Heilbrun L, Camann D, Yau A, Schultz S, Elisco V, Tapia B, Garza N, Miller C. {{Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples}}. {Journal of environmental and public health}. 2015;2015:862414.
Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD) were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013), we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.
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9. Vice MA, Nahar VK, Ford MA, Bass MA, Johnson AK, Davis AB, Biviji-Sharma R. {{Risk Factors for Low Bone Mineral Density in Institutionalized Individuals with Developmental Disabilities}}. {Health promotion perspectives}. 2015;5(2):147-52.
BACKGROUND: Persons with intellectual/developmental disabilities (IDD) are exposed to several factors, which have been determined as risks for osteoporosis. Many of these individuals are non-ambulatory, resulting in lack of weight bearing activity, which is well established as a major contributor to bone loss. The purpose of this study was to investigate risk factors for low bone mineral density (BMD) in persons with IDD residing in residential facilities. METHODS: This cross-sectional study was conducted at an Intermediate Care Facility for individuals with Intellectual and Developmental Disabilities (ICF/IDD). Medical records data were used from 69 individuals, including heal scan T-scores, nutritional, pharmacologic and other risk factors. Chi-Square analysis was used to determine relationships between the variables. RESULTS: BMD measures were not significantly associated with age, gender, height, weight, or BMI for this population (P > 0.05). The association between BMD diagnoses and DSM-IV classification of mental retardation approached significance (P = 0.063). A significant association was found with anti-seizure medication (P = 0.009). CONCLUSION: Follow-up studies should focus on how supplementation and medication changes may or may not alter BMD. Persons with IDD are experiencing longer life expectancies, and therefore, studies ascertaining information on diseases associated with this aging population are warranted.
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10. Zeidler S, Hukema RK, Willemsen R. {{The quest for targeted therapy in fragile X syndrome}}. {Expert opinion on therapeutic targets}. 2015 Aug 21:1-5.
Fragile X syndrome (FXS) is the most common, monogenetic cause of intellectual disability and autism-spectrum disorders. Although there is no effective therapy, greater understanding of disturbed neuronal pathways has introduced options for targeted therapy. But whereas many FXS phenotypes were improved in preclinical studies with drugs targeting these pathways in the FXS mouse model, attempts to translate these animal-model success stories into treatment of patients in clinical trials have been extremely disappointing. Complicating factors, particularly in animal studies, include mouse inbred strains, variability in functional studies between laboratories, publication bias and lack of reliable and objective primary outcome measures in both mice and patients. Possibly most important, however, is one factor that has been little explored: the complexity of the molecular imbalance in FXS and the need to simultaneously target several different disturbed pathways and different cellular compartments. New, well-conceived animal studies should generate more productive approaches in the quest for targeted therapy for FXS.
