1. Abu-Amero KK, Hellani AM, Salih MA, Seidahmed MZ, Elmalik TS, Zidan G, Bosley TM. {{A de novo marker chromosome derived from 9p in a patient with 9p partial duplication syndrome and autism features: genotype-phenotype correlation}}. {BMC Med Genet} (Sep 21);11(1):135.
ABSTRACT: BACKGROUND: Previous studies focusing on candidate genes and chromosomal regions identified several copy number variations (CNVs) associated with increased risk of autism or autism spectrum disorders (ASD). Case Presentation: We describe a 17-year-old girl with autism, severe mental retardation, epilepsy, and partial 9p duplication syndrome features in whom GTG-banded chromosome analysis revealed a female karyotype with a marker chromosome in 69% of analyzed metaphases. Array CGH analysis showed that the marker chromosome originated from 9p24.3 to 9p13.1 with a gain of 38.9 Mb. This mosaic 9p duplication was detected only in the proband and not in the parents, her four unaffected siblings, or 258 ethnic controls. Apart from the marker chromosome, no other copy number variations (CNVs) were detected in the patient or her family. Detailed analysis of the duplicated region revealed: i) an area extending from 9p22.3 to 9p22.2 that was previously identified as a critical region for the 9p duplication syndrome; ii) a region extending from 9p22.1 to 9p13.1 that was previously reported to be duplicated in a normal individual; and iii) a potential ASD locus extending from 9p24.3 to 9p23. The ASD candidate locus contained 34 genes that may contribute to the autistic features in this patient. CONCLUSION: We identified a potential ASD locus (9p24.3 to 9p23) that may encompass gene(s) contributing to autism or ASD.
2. Frankel F, Whitham C. {{Parent-assisted Group Treatment for Friendship Problems of Children with Autism Spectrum Disorders}}. {Brain Res} (Sep 18)
Children with Asperger’s Disorder or High functioning Autism are included in regular education classes but find themselves excluded from the social lives of their classmates. This paper briefly reviews studies which attempt to provide them with training to overcome their social difficulties. These interventions have had limited success and have not systematically incorporated the child’s parents into the intervention. Children’s Friendship Training is a manualized parent-assisted group treatment which teaches social skill through learning and practicing sets of rules of etiquette for key social situations. The treatment approach has been demonstrated to have success in improving friendships of children with Autism Spectrum Disorders. The content of Children’s Friendship Training is briefly described and results of controlled studies are reviewed. Limitations of previous research and future directions are also described.
3. Hagerman R, Hoem G, Hagerman P. {{Fragile X and autism: Intertwined at the molecular level leading to targeted treatments}}. {Mol Autism} (Sep 21);1(1):12.
ABSTRACT: Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5′ untranslated portion of the fragile mental retardation 1 gene (FMR1), leading to deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA carrier protein that controls the translation of several other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS cases, and pervasive developmental disorder, not otherwise specified (PDD-NOS) occurs in an additional 30% of cases. Premutation repeat expansions (55 to 200 CGG repeats) may also give rise to autism spectrum disorders (ASD), including both autism and PDD-NOS, through a different molecular mechanism that involves a direct toxic effect of the expanded CGG repeat FMR1 mRNA. RNA toxicity can also lead to aging effects including tremor, ataxia and cognitive decline, termed fragile X-associated tremor ataxia syndrome (FXTAS), in premutation carriers in late life. In studies of mice bearing premutation expansions, there is evidence of early postnatal neuronal cell toxicity, presenting as reduced cell longevity, decreased dendritic arborization and altered synaptic morphology. There is also evidence of mitochondrial dysfunction in premutation carriers. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in autism without fragile X mutations. Research regarding dysregulation of neurotransmitter systems in FXS, including the metabotropic glutamate receptor (mGluR)1/5 pathway and aminobutyric acid (GABA)A pathways, have led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism.
4. Haltigan JD, Ekas NV, Seifer R, Messinger DS. {{Brief Report: Attachment Security in Infants At-Risk for Autism Spectrum Disorders}}. {J Autism Dev Disord} (Sep 22)
Little is known about attachment security and disorganization in children who are at genetic risk for an Autism Spectrum Disorder (ASD) prior to a possible diagnosis. The present study examined distributions of attachment security and disorganization at 15-months of age in a sample of infant siblings of older children with (ASD-sibs; n = 51) or without (COMP-sibs; n = 34) an ASD. ASD-sibs were not more or less likely to evince attachment insecurity or disorganization than COMP-sibs. However, relative to COMP-sibs, the rate of B1-B2 secure subclassifications was disproportionately larger in the ASD-sib group. Results suggest that ASD-sibs are not less likely to form secure affectional bonds with their caregivers than COMP-sibs, but may differ from COMP-sibs in their expression of attachment security.
5. Noriuchi M, Kikuchi Y, Yoshiura T, Kira R, Shigeto H, Hara T, Tobimatsu S, Kamio Y. {{Altered white matter fractional anisotropy and social impairment in children with autism spectrum disorder}}. {Brain Res} (Sep 18)
Individuals with autism spectrum disorder (ASD) have severe difficulties in social interaction and communication, as well as restricted and/or stereotyped patterns of behavior. Previous studies have suggested that abnormal neural connectivity might be associated with higher information processing dysfunction involving social impairment. However, the white matter structure in ASD is poorly understood. To explore this, we conducted a voxel-based, whole-brain diffusion tensor imaging (DTI) analysis to determine fractional anisotropy (FA), lambda(1), lambda(2) and lambda(3) in high-functioning children with ASD compared with age-, gender-, and handedness-matched healthy control participants. We then investigated whether DTI parameters were associated with behaviorally measured social function. We found that FA and lambda(1) were significantly lower in the ASD group than in the control group in the white matter around left dorsolateral prefrontal cortex (DLPFC), posterior superior temporal sulcus/temporo-parietal junction, right temporal pole, amygdala, superior longitudinal fasciculus, occipitofrontal fasciculus, mid- and left anterior corpus callosum (aCC), and mid- and right anterior cingulate cortex. The FA values in the left DLPFC was negatively correlated with the degree of social impairment in children with ASD. Higher lambda(1) values were observed in the cerebellar vermis lobules in the ASD group. The white matter alterations in children with ASD were around cortical regions that play important roles in social cognition and information integration. These DTI results and their relationship to social impairment add to evidence of cerebral and cerebellar white matter structural abnormalities in ASD.
6. Oblak AL, Gibbs TT, Blatt GJ. {{Reduced GABA(A) receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism}}. {Brain Res} (Sep 18)
Individuals with autism display deficits in the social domain including the proper recognition of faces and interpretations of facial expressions. There is an extensive network of brain regions involved in face processing including the fusiform gyrus (FFG) and posterior cingulate cortex (PCC). Functional imaging studies have found that controls have increased activity in the PCC and FFG during face recognition tasks, and the FFG has differential responsiveness in autism when viewing faces. Multiple lines of evidence have suggested that the GABAergic system is disrupted in the brains of individuals with autism and it is likely that altered inhibition within the network influences the ability to perceive emotional expressions. On-the-slide ligand binding autoradiography was used to determine if there were alterations in GABA(A) and/or benzodiazepine binding sites in the brain in autism. Using (3)H-muscimol and (3)H-flunitrazepam we could determine whether the number (B(max)), binding affinity (K(d)), and/or distribution of GABA(A) receptors and its benzodiazepine binding sites (BZD) differed from controls in the FFG and PCC. Significant reductions in the number of GABA(A) receptors and BZD binding sites in the superficial layers of the PCC and FFG, and in the number of BZD binding sites were found in the deep layers of the FFG. In addition, the autism group had a higher binding affinity in the superficial layers of the GABA(A) study. Taken together, these findings suggest that the disruption in inhibitory control in the cortex may contribute to the core disturbances of socio-emotional behaviors in autism.
7. Stahmer AC, Schreibman L, Cunningham AB. {{Towards a Technology of Treatment Individualization for Young Children with Autism Spectrum Disorders}}. {Brain Res} (Sep 18)
Although the etiology of autism spectrum disorders (ASD) and early development of the ASD are not yet well understood, recent research in the field of autism has heavily emphasized the importance of early intervention (i.e. treatment before the age of 4 years). Currently, several methods have been demonstrated to be efficacious with some children however no treatment completely ameliorates the symptoms of ASD or works for all children with the disorder. The heterogeneity and developmental nature of the disorder make it unlikely that one specific treatment will be best for all children, or will work for any one child throughout his or her educational career. Thus, this paper examines early research validating different technologies for individualizing treatment. A discussion of current research on pre-treatment characteristics associated with differential outcomes in treatment, including child, family, and practitioner variables; and how specific intervention techniques address each of those pre-treatment characteristics is provided. The ultimate goal of this line of research is to enable practitioners to prospectively tailor treatments to specific children and increase the overall rate of positives outcomes for children with autism. Research that furthers understanding of how to match clients with efficacious treatments will decrease the outcome variability that characterizes early intervention research at present, and provide for the most efficient allocation of resources during the critical early intervention time-period. This type of research is in its infancy, but is imperative if we are to determine a priori which treatment method will be most effective for a specific child.
8. Wang LS, Hranilovic D, Wang K, Lindquist IE, Yurcaba L, Petkovic ZB, Gidaya N, Jernej B, Hakonarson H, Bucan M. {{Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia}}. {BMC Med Genet} (Sep 21);11(1):134.
ABSTRACT: BACKGROUND: Genome-wide studies on autism spectrum disorders (ASDs) have mostly focused on large-scale population samples, but examination of rare variations in isolated populations may provide additional insights into the disease pathogenesis. METHODS: As a first step in the genetic analysis of ASD in Croatia, we characterized genetic variation in a sample of 103 subjects with ASD and 203 control individuals, who were genotyped using the Illumina HumanHap550 BeadChip. We analyzed the genetic diversity of the Croatian population and its relationship to other populations, the degree of relatedness via Runs of Homozygosity (ROHs), and the distribution of large (>500Kb) copy number variations. RESULTS: Combining the Croatian cohort with several previously published populations in the FastME analysis (an alternative to Neighbor Joining) revealed that Croatian subjects cluster, as expected, with Southern Europeans; in addition, individuals from the same geographic region within Europe cluster together. Whereas Croatian subjects could be separated from a sample of healthy control subjects of European origin from North America, Croatian ASD cases and controls are well mixed. A comparison of runs of homozygosity indicated that the number and the median length of regions of homozygosity are higher for ASD subjects than for controls (p=6×10^-3). Furthermore, analysis of copy number variants found a higher frequency of large chromosomal rearrangements (> 2Mb) in ASD cases (5/103) than in ethnically matched control subjects (1/197, p=0.019). CONCLUSIONS: Our findings illustrate the remarkable utility of high-density genotype data for subjects from a limited geographic area in dissecting genetic heterogeneity with respect to population and disease related variation.
9. Wang P, Michaels CA, Day MS. {{Stresses and Coping Strategies of Chinese Families with Children with Autism and Other Developmental Disabilities}}. {J Autism Dev Disord} (Sep 22)
Data from 368 families of children with autism and other developmental disabilities in the People’s Republic of China were gathered to understand the stresses that families experience and the coping strategies they employ. Chinese families of children with developmental disabilities perceived high levels of stress related to pessimism, child characteristics, and parent and family problems. Regarding coping strategies, acceptance, active coping, positive reinterpretation and growth, suppression of competing activities, and planning were the most frequently employed coping strategies. Parents of children with autism experienced more stress and used planning as a coping strategy to a greater degree than parents of children with other developmental disabilities. The implications and limitations of these findings are discussed.
