1. Ameis SH, Fan J, Rockel C, Voineskos AN, Lobaugh NJ, Soorya L, Wang AT, Hollander E, Anagnostou E. {{Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study}}. {PLoS One};2011;6(11):e28044.
BACKGROUND: Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD. METHODS/PRINCIPAL FINDINGS: DTI scans were acquired for 19 children and adolescents with ASD ( approximately 8-18 years; mean 12.4+/-3.1) and 16 age and IQ matched controls ( approximately 8-18 years; mean 12.3+/-3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii), children only (</=12 yrs.), and (iii) adolescents only (>12 yrs.) were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing. CONCLUSIONS/SIGNIFICANCE: Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder.
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2. Cop E, Oner P, Oner O. {{Risperidone and Double Incontinence in a Child with Autism}}. {J Child Adolesc Psychopharmacol};2011 (Dec 2)
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3. Duerden EG, Mak-Fan KM, Taylor MJ, Roberts SW. {{Regional differences in grey and white matter in children and adults with autism spectrum disorders: an activation likelihood estimate (ALE) meta-analysis}}. {Autism Res};2011 (Dec 2)
Structural alterations in brain morphology have been inconsistently reported in children compared to adults with autism spectrum disorder (ASD). We assessed these differences by performing meta-analysis on the data from 19 voxel-based morphometry studies. Common findings across the age groups were grey matter reduction in left putamen and medial prefrontal cortex (mPFC) and grey matter increases in the lateral PFC, while white matter decreases were seen mainly in the children in frontostriatal pathways. In the ASD sample, children/adolescents were more likely than adults to have increased grey matter in bilateral fusiform gyrus, right cingulate and insula. Results show that clear maturational differences exist in social cognition and limbic processing regions only in children/adolescents and not in adults with ASD, and may underlie the emotional regulation that improves with age in this population. Autism Res 2011,4:xxx-xxx. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Erickson CA, Early M, Stigler KA, Wink LK, Mullett JE, McDougle CJ. {{An Open-Label Naturalistic Pilot Study of Acamprosate in Youth with Autistic Disorder}}. {J Child Adolesc Psychopharmacol};2011 (Dec 2)
Abstract To date, placebo-controlled drug trials targeting the core social impairment of autistic disorder (autism) have had uniformly negative results. Given this, the search for new potentially novel agents targeting the core social impairment of autism continues. Acamprosate is U.S. Food and Drug Administration-approved drug to treat alcohol dependence. The drug likely impacts both gamma-aminobutyric acid and glutamate neurotransmission. This study describes our initial open-label experience with acamprosate targeting social impairment in youth with autism. In this naturalistic report, five of six youth (mean age, 9.5 years) were judged treatment responders to acamprosate (mean dose 1,110 mg/day) over 10 to 30 weeks (mean duration, 20 weeks) of treatment. Acamprosate was well tolerated with only mild gastrointestinal adverse effects noted in three (50%) subjects.
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5. Kern JK, Geier DA, Adams JB, Garver CR, Audhya T, Geier MR. {{A clinical trial of glutathione supplementation in autism spectrum disorders}}. {Med Sci Monit};2011 (Dec 1);17(12):CR677-682.
Background: Recent evidence shows that subjects diagnosed with an autism spectrum disorder (ASD) have significantly lower levels of glutathione than typically developing children. The purpose of this study was to examine the use of two commonly used glutathione supplements in subjects diagnosed with an ASD to determine their efficacy in increasing blood glutathione levels in subjects diagnosed with an ASD.<br /> Material/Methods: The study was an eight-week, open-label trial using oral lipoceutical glutathione (n=13) or transdermal glutathione (n=13) in children, 3-13 years of age, with a diagnosis of an ASD. Subjects underwent pre- and post-treatment lab testing to evaluate plasma reduced glutathione, oxidized glutathione, cysteine, taurine, free and total sulfate, and whole-blood glutathione levels.<br /> Results: The oral treatment group showed significant increases in plasma reduced glutathione, but not whole-blood glutathione levels following supplementation. Both the oral and transdermal treatment groups showed significant increases in plasma sulfate, cysteine, and taurine following supplementation.<br /> Conclusions: The results suggest that oral and transdermal glutathione supplementation may have some benefit in improving some of the transsulfuration metabolites. Future studies among subjects diagnosed with an ASD should further explore the pharmacokinetics of glutathione supplementation and evaluate the potential effects of glutathione supplementation upon clinical symptoms.<br />
6. Losh M, Esserman D, Anckarsater H, Sullivan PF, Lichtenstein P. {{Lower birth weight indicates higher risk of autistic traits in discordant twin pairs}}. {Psychol Med};2011 (Dec 2):1-12.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder of complex etiology. Although strong evidence supports the causal role of genetic factors, environmental risk factors have also been implicated. This study used a co-twin-control design to investigate low birth weight as a risk factor for ASD.MethodWe studied a population-based sample of 3715 same-sex twin pairs participating in the Child and Adolescent Twin Study of Sweden (CATSS). ASD was assessed using a structured parent interview for screening of ASD and related developmental disorders, based on DSM-IV criteria. Birth weight was obtained from medical birth records maintained by the Swedish Medical Birth Registry. RESULTS: Twins lower in birth weight in ASD-discordant twin pairs (n=34) were more than three times more likely to meet criteria for ASD than heavier twins [odds ratio (OR) 3.25]. Analyses of birth weight as a continuous risk factor showed a 13% reduction in risk of ASD for every 100 g increase in birth weight (n=78). Analysis of the effect of birth weight on ASD symptoms in the entire population (most of whom did not have ASD) showed a modest association. That is, for every 100 g increase in birth weight, a 2% decrease in severity of ASD indexed by scores on the Autism – Tics, attention-deficit hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC) inventory would be expected in the sample as a whole. CONCLUSIONS: The data were consistent with the hypothesis that low birth weight confers risk to ASD. Thus, although genetic effects are of major importance, a non-genetic influence associated with birth weight may contribute to the development of ASD.
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7. Takahashi S, Matsumoto N, Okayama A, Suzuki N, Araki A, Okajima K, Tanaka H, Miyamoto A. {{FOXG1 mutations in Japanese patients with the congenital variant of Rett syndrome}}. {Clin Genet};2011 (Dec 1)
Rett syndrome is a severe neurodevelopmental disorder characterized by microcephaly, psychomotor regression, seizures and stereotypical hand movements. Recently, deletions and inactivating mutations in FOXG1, encoding a brain-specific transcription factor that is critical for forebrain development, have been found to be associated with the congenital variant of Rett syndrome. Here, we report the clinical features and molecular characteristics of 2 cases of the congenital variant of Rett syndrome. We conducted mutation screenings of FOXG1 in a cohort of 15 Japanese patients with a clinical diagnosis of atypical Rett syndrome but without MECP2 and CDKL5 mutations. Two unrelated female patients had heterozygous mutations (c.256dupC, p.Gln86ProfsX35 and c.689G>A, pArg230His). Both showed neurological symptoms from the neonatal period, including hypotonia, irritability and severe microcephaly. Further, their psychomotor development was severely impaired, as indicated by their inability to sit unaided or acquire speech sounds, and they had a hyperkinetic movement disorder, because both displayed hand stereotypies and jerky movements of the upper limbs. Brain MRI scans revealed delayed myelination with hypoplasia of the corpus callosum and frontal lobe. These cases confirm the involvement of FOXG1 in the molecular etiology of the congenital variant of Rett syndrome and demonstrate the characteristic features of FOXG1-related disorder.
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8. Theoharides TC, Zhang B. {{Neuro-Inflammation, Blood-Brain Barrier, Seizures and Autism}}. {J Neuroinflammation};2011 (Nov 30);8(1):168.
ABSTRACT: Many children with Autism Spectrum Diseases (ASD) present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that and mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.
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9. Vignoli A, La Briola F, Peron A, Turner K, Savini M, Cogliati F, Russo S, Canevini MP. {{Medical care of adolescents and women with Rett syndrome: An Italian study}}. {Am J Med Genet A};2011 (Dec 2)
Rett syndrome (RTT) is a rare neurodevelopmental disorder, linked to MECP2 gene mutations in the majority of cases, which results in severe disability and is associated with several comorbidities. The clinical condition of RTT patients tends to stabilize over time, and prolonged survival has recently been demonstrated. However, limited information is available on the long-term course of older patients with RTT, especially among those in Southern Europe. The aim of our study is to evaluate the main clinical features and state of health of adult Italian patients with RTT and to present their evolution over time, identifying major clinical issues present at different ages. A total of 130 families of patients with RTT aged >/=14 years were asked to complete a questionnaire, 84 of which were returned (65%). Among the clinical characteristics of RTT, stereotypies and poor hand function and feeding ability remained stable over time, while nonverbal communication tended to improve. With regard to the main pathologies, sleep, behavioral, and autonomic disorders persisted into adulthood, while epilepsy improved and musculoskeletal problems worsened. In our sample, older patients with R294X and R133C mutations and with C-terminal deletions showed lower levels of clinical severity. The development of guidelines for the clinical management of patients with RTT will assist health care providers in dealing with the complex RTT phenotype. More extensive data about the long-term course of the condition could help in the design of programs for secondary prevention of disabilities for younger females affected by the syndrome. (c) 2011 Wiley Periodicals, Inc.
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10. Visootsak J, Charen K, Rohr J, Allen E, Sherman S. {{Diagnosis of Fragile X Syndrome: A Qualitative Study of African American Families}}. {J Genet Couns};2011 (Dec 2)
Fragile X syndrome (FXS) is an inherited genetic condition with critical consequences to the proband and family members at all levels in the generations. Although evidence demonstrates that the rates of diagnosis for FXS are the same in all racial groups, age of diagnosis in African American children has been reported to occur later than in Caucasian children. Additionally, African American families are seriously under-represented in existing FXS research studies. As such, it is important to understand the possible disparities in the underlying factors to receiving a diagnosis in African American families with FXS. Herein, a qualitative approach was adopted to describe the overall FXS diagnosis experiences (pre-diagnosis, diagnosis, and post-diagnosis stages) of a convenience sample of 10 African American mothers. We identified three major findings among our participants: (1) FXS testing is not ordered immediately once a parent expresses concerns of developmental delays to the pediatricians, (2) the diagnosis is sometimes delivered in an insensitive manner with information often being outdated and unbalanced towards negative aspects, (3) communication issues among family members exists once the diagnosis is discovered. Although these qualitative data may not be representative of the whole group, these findings have significant implications for genetic counseling and our understanding in providing support and advocacy for African American families with FXS.
