1. Anagnostou E, Soorya L, Brian J, Dupuis A, Mankad D, Smile S, Jacob S. {{Intranasal oxytocin in the treatment of autism spectrum disorders: A review of literature and early safety and efficacy data in youth}}. {Brain research}. 2014 Sep 11;1580:188-98.
BACKGROUND: There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. METHODS: Fifteen children and adolescents with verbal IQs>/=70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. RESULTS: Among 4 doses tested, the highest dose evaluated, 0.4IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. CONCLUSIONS: This pilot study suggests that daily administration of intranasal oxytocin at 0.4IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav.
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2. Gore AC, Martien KM, Gagnidze K, Pfaff D. {{Implications of prenatal steroid perturbations for neurodevelopment, behavior, and autism}}. {Endocrine reviews}. 2014 Sep 11:er20131122.
The prenatal brain develops under the influence of an ever-changing hormonal milieu that includes endogenous fetal gonadal and adrenal hormones; placental and maternal hormones; and exogenous substances with hormonal activity that can cross the placental barrier. This review discusses the influences of endogenous fetal and maternal hormones on normal brain development, and potential consequences of pathophysiological hormonal perturbations to the developing brain, with particular reference to autism. We also consider the effects of hormonal pharmaceuticals used for assisted reproduction, the maintenance of pregnancy, the prevention of congenital adrenal hypertrophy, and hormonal contraceptives continued into an unanticipated pregnancy, among others. These treatments, while in some instances life-saving, may have unintended consequences on the developing fetuses. Additional concern is raised by fetal exposures to endocrine-disrupting chemicals (EDCs) encountered universally by pregnant women from food/water containers, contaminated food, household chemicals, and other sources. What are the potential outcomes of prenatal steroid perturbations on neurodevelopmental and behavioral disorders, including autism spectrum disorders? Our purposes here are: (i.) to summarize some consequences of steroid exposures during pregnancy for the development of brain and behavior in the offspring; (ii.) to summarize what is known about the relationships between exposures and behavior, including autism spectrum disorders; (iii.) to discuss the molecular underpinnings of such effects, especially molecular epigenetic mechanisms of prenatal steroid manipulations, a field that may explain effects of direct exposures, and even transgenerational effects; and (iv.) for all of these, to add cautionary notes about their interpretation in the name of scientific rigor.
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3. Misra V. {{The social brain network and autism}}. {Annals of neurosciences}. 2014 Apr;21(2):69-73.
Available research data in Autism suggests the role of a network of brain areas, often known as the ‘social brain’. Recent studies highlight the role of genetic mutations as underlying patho-mechanism in Autism. This mini review, discusses the basic concepts behind social brain networks, theory of mind and genetic factors associated with Autism. It critically evaluates and explores the relationship between the behavioral outcomes and genetic factors providing a conceptual framework for understanding of autism.
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4. Nolin SL, Glicksman A, Ersalesi N, Dobkin C, Brown WT, Cao R, Blatt E, Sah S, Latham GJ, Hadd AG. {{Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers}}. {Genetics in medicine : official journal of the American College of Medical Genetics}. 2014 Sep 11.
Purpose:Fragile X CGG repeat alleles often contain one or more AGG interruptions that influence allele stability and risk of a full mutation transmission from parent to child. We have examined transmissions of maternal and paternal alleles with 45-90 repeats to quantify the effect of AGG interruptions on fragile X repeat instability.Methods:A novel FMR1 polymerase chain reaction assay was used to determine CGG repeat length and AGG interruptions for 1,040 alleles from 705 families.Results:We grouped transmissions into nine categories of five repeats by parental size and found that in every size category, alleles with no AGGs had the greatest risk for instability. For maternal alleles <75 repeats, 89% (24/27) that expanded to a full mutation had no AGGs. Two contractions in maternal transmission were accompanied by loss of AGGs, suggesting a mechanism for generating alleles that lack AGG interruptions. Maternal age was examined as a factor in full mutation expansions using prenatal samples to minimize ascertainment bias, and a possible effect was observed though it was not statistically significant (P = 0.06).Conclusion:These results strengthen the association of AGG repeats with CGG repeat stability and provide more accurate risk estimates of full mutation expansions for women with 45-90 repeat alleles.Genet Med advance online publication 11 September 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.106.
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5. Pugliese CE, Fritz MS, White SW. {{The role of anger rumination and autism spectrum disorder-linked perseveration in the experience of aggression in the general population}}. {Autism}. 2014 Sep 11.
This study (a) examined the role of anger rumination as a mediator of the relation between social anxiety and the experience of anger, hostility, and aggression, in the general population, and (b) evaluated the degree to which the presence of autism spectrum disorder characteristics moderates the indirect influence of anger rumination. We then explored whether social cognition and perseveration characteristic of autism spectrum disorder uniquely accounted for the predicted moderation. In this survey study of young adults (n = 948), anger rumination mediated the relation between social anxiety and hostility, as well as verbal and physical aggression, as predicted. Greater autism spectrum disorder characteristics augmented the effect of social anxiety on hostility and physical aggression by increasing the effect of anger rumination, but not by increasing the effect of social anxiety on anger rumination. Implications for developing treatment approaches that target hostility and aggression among young adults who may not be formally diagnosed but have characteristics of autism spectrum disorder are discussed.
