1. Anderson A, Locke J, Kretzmann M, Kasari C. {{Social network analysis of children with autism spectrum disorder: Predictors of fragmentation and connectivity in elementary school classrooms}}. {Autism};2015 (Nov 13)
Although children with autism spectrum disorder are frequently included in mainstream classrooms, it is not known how their social networks change compared to typically developing children and whether the factors predictive of this change may be unique. This study identified and compared predictors of social connectivity of children with and without autism spectrum disorder using a social network analysis. Participants included 182 children with autism spectrum disorder and 152 children without autism spectrum disorder, aged 5-12 years in 152 general education K-5 classrooms. General linear models were used to compare how age, classroom size, gender, baseline connectivity, diagnosis, and intelligence quotient predicted changes in social connectivity (closeness). Gender and classroom size had a unique interaction in predicting final social connectivity and the change in connectivity for children with autism spectrum disorder; boys who were placed in larger classrooms showed increased social network fragmentation. This increased fragmentation for boys when placed in larger classrooms was not seen in typically developing boys. These results have implications regarding placement, intervention objectives, and ongoing school support that aimed to increase the social success of children with autism spectrum disorder in public schools.
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2. Bhandari R, Kuhad A. {{Neuropsychopharmacotherapeutic efficacy of curcumin in experimental paradigm of autism spectrum disorders}}. {Life Sci};2015 (Nov 15);141:156-169.
AIM: Neuroinflammatory response triggered by the stimulation of matrix metalloproteinases plays a pivotal role in the development of autistic phenotype. MMPs stimulate inflammatory cytokines release along with mitochondrial deficits that ultimately lead to neuronal dysfunction and precipitate autistic symptoms. The aim of the present study was to explore the neuropsychopharmacotherapeutic efficacy of curcumin in the experimental paradigm of autism spectrum disorders. MATERIALS AND METHODS: 1M propanoic acid (4mul) was infused over 10min into the anterior portion of the caudoputamen to induce autistic behavior in rats. Curcumin (50, 100 and 200mg/kg) was administered per orally starting from 2nd day of surgery and continued up to 28th day. Rats were tested for various neurobehavioural paradigms like social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning and memory as well as for repetitive and pervasive behavior. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-alpha and MMP-9 were also carried out. KEY FINDINGS: Intracerebroventricular injection of propanoic acid produced neurological, sensory, behavioral, biochemical and molecular deficits which were assessed as endophenotype of autism spectrum disorders. Regular treatment with curcumin for four weeks significantly and dose dependently restored neurological, behavioral, biochemical and molecular changes associated with autistic phenotype in rats. SIGNIFICANCE: The major finding of the study is that curcumin restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-alpha and MMP-9 in PPA-induced autism in rats. Therefore, curcumin can be developed as a potential neuropsychopharmacotherapeutic adjunct for autism spectrum disorders (ASD).
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3. Goldschmidt J. {{Nutritional Status and Autism Spectrum Disorders}}. {Adv Nutr};2015 (Nov);6(6):865.
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4. Jaworski JL, Eigsti IM. {{Low-level visual attention and its relation to joint attention in autism spectrum disorder}}. {Child Neuropsychol};2015 (Nov 15):1-16.
Visual attention is integral to social interaction and is a critical building block for development in other domains (e.g., language). Furthermore, atypical attention (especially joint attention) is one of the earliest markers of autism spectrum disorder (ASD). The current study assesses low-level visual attention and its relation to social attentional processing in youth with ASD and typically developing (TD) youth, aged 7 to 18 years. The findings indicate difficulty overriding incorrect attentional cues in ASD, particularly with non-social (arrow) cues relative to social (face) cues. The findings also show reduced competition in ASD from cues that remain on-screen. Furthermore, social attention, autism severity, and age were all predictors of competing cue processing. The results suggest that individuals with ASD may be biased towards speeded rather than accurate responding, and further, that reduced engagement with visual information may impede responses to visual attentional cues. Once attention is engaged, individuals with ASD appear to interpret directional cues as meaningful. These findings from a controlled, experimental paradigm were mirrored in results from an ecologically valid measure of social attention. Attentional difficulties may be exacerbated during the complex and dynamic experience of actual social interaction. Implications for intervention are discussed.
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5. Stutzman D, Dopheide J. {{Acetylcysteine for treatment of autism spectrum disorder symptoms}}. {Am J Health Syst Pharm};2015 (Nov 15);72(22):1956-1959.
PURPOSE: Successful use of acetylcysteine to control irritability and aggressive behaviors in a hospitalized adolescent patient with autism spectrum disorder (ASD) is described. SUMMARY: A 17-year-old Hispanic male with ASD and intellectual disability was hospitalized for inpatient psychiatric treatment due to impulsive and violent behavior. Despite receiving various medications in the initial weeks of hospitalization, including intramuscular lorazepam and diphenhydramine injections (four days a week on average), the patient continued to exhibit aggressive and unpredictable behaviors. Treatment with 20% acetylcysteine oral solution was initiated at a dosage of 600 mg twice daily as an adjunct to quetiapine therapy. Over the next six weeks, reductions in the patient’s aggressive behavior, tantrums, and irritability were noted. The use of as-needed medications to control aggression was decreased, and the dosage of quetiapine was lowered from 700 to 400 mg daily over the course of the hospitalization. Acetylcysteine was well tolerated, with no observed or reported adverse effects. Unlike clonidine or guanfacine (other medications used for ASD-related behavioral symptoms), acetylcysteine is not sedating; moreover, it lacks the metabolic, extrapyramidal, and endocrine adverse effects of atypical antipsychotics. Published data from small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; these therapeutic benefits may be associated with acetylcysteine’s glutamatergic, dopaminergic, antioxidant, and anti-inflammatory properties. CONCLUSION: Treatment with acetylcysteine improved ASD symptoms, including irritability and aggression, in a teenage patient.
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6. Wahlstrom-Helgren S, Klyachko VA. {{GABAB receptor-mediated feed-forward circuit dysfunction in the mouse model of fragile X syndrome}}. {J Physiol};2015 (Nov 15);593(22):5009-5024.
KEY POINTS: Cortico-hippocampal feed-forward circuits formed by the temporoammonic (TA) pathway exhibit a marked increase in excitation/inhibition ratio and abnormal spike modulation functions in Fmr1 knock-out (KO) mice. Inhibitory, but not excitatory, synapse dysfunction underlies cortico-hippocampal feed-forward circuit abnormalities in Fmr1 KO mice. GABA release is reduced in TA-associated inhibitory synapses of Fmr1 KO mice in a GABAB receptor-dependent manner. Inhibitory synapse and feed-forward circuit defects are mediated predominately by presynaptic GABAB receptor signalling in the TA pathway of Fmr1 KO mice. GABAB receptor-mediated inhibitory synapse defects are circuit-specific and are not observed in the Schaffer collateral pathway-associated inhibitory synapses in stratum radiatum. ABSTRACT: Circuit hyperexcitability has been implicated in neuropathology of fragile X syndrome, the most common inheritable cause of intellectual disability. Yet, how canonical unitary circuits are affected in this disorder remains poorly understood. Here, we examined this question in the context of the canonical feed-forward inhibitory circuit formed by the temporoammonic (TA) branch of the perforant path, the major cortical input to the hippocampus. TA feed-forward circuits exhibited a marked increase in excitation/inhibition ratio and major functional defects in spike modulation tasks in Fmr1 knock-out (KO) mice, a fragile X mouse model. Changes in feed-forward circuits were caused specifically by inhibitory, but not excitatory, synapse defects. TA-associated inhibitory synapses exhibited increase in paired-pulse ratio and in the coefficient of variation of IPSPs, consistent with decreased GABA release probability. TA-associated inhibitory synaptic transmission in Fmr1 KO mice was also more sensitive to inhibition of GABAB receptors, suggesting an increase in presynaptic GABAB receptor (GABAB R) signalling. Indeed, the differences in inhibitory synaptic transmission between Fmr1 KO and wild-type (WT) mice were eliminated by a GABAB R antagonist. Inhibition of GABAB Rs or selective activation of presynaptic GABAB Rs also abolished the differences in the TA feed-forward circuit properties between Fmr1 KO and WT mice. These GABAB R-mediated defects were circuit-specific and were not observed in the Schaffer collateral pathway-associated inhibitory synapses. Our results suggest that the inhibitory synapse dysfunction in the cortico-hippocampal pathway of Fmr1 KO mice causes hyperexcitability and feed-forward circuit defects, which are mediated in part by a presynaptic GABAB R-dependent reduction in GABA release.
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7. Westmark CJ. {{The quest for fragile X biomarkers}}. {Mol Cell Pediatr};2014 (Dec);1(1):1.
BACKGROUND: Fragile X is the most common form of inherited intellectual disability and the leading known genetic cause of autism. There is currently no cure or approved medication for fragile X although various drugs target specific disease symptoms and a large number of therapeutics are in various stages of clinical development. Multiple recent clinical trials have failed on their primary endpoints indicating that there is a compelling need for validated biomarkers and outcome measures in fragile X. FINDINGS: There are currently no validated blood-based biomarkers to assess disease severity or to monitor drug efficacy in fragile X syndrome. Herein, we review candidate blood protein biomarkers including extracellular-regulated kinase, phosphoinositide 3-kinase, matrix metalloproteinase 9, amyloid-beta and amyloid-beta protein precursor. CONCLUSIONS: Bench-to-bedside plans for fragile X syndrome are severely limited by the lack of validated outcome measures. The reviewed candidate biomarkers are at early stages of validation and deserve further investigation.
