1. Callahan K, Shukla-Mehta S, Magee S, Wie M. {{ABA Versus TEACCH: The Case for Defining and Validating Comprehensive Treatment Models in Autism}}. {J Autism Dev Disord};2009 (Aug 1)
The authors analyzed the results of a social validation survey to determine if autism service providers including special education teachers, parents, and administrators demonstrate a preference for the intervention components of Applied Behavior Analysis or Training and Education of Autistic and other Communication Handicapped Children. They also investigated the comprehensiveness of these treatment models for use in public school programs. The findings indicate no clear preference for either model, but a significantly higher level of social validity for components inherent in both approaches. The authors discuss the need for research to define what is meant by comprehensive programming in autism.
2. Carreira IM, Melo JB, Rodrigues C, Backx L, Vermeesch J, Weise A, Kosyakova N, Oliveira G, Matoso E. {{Molecular cytogenetic characterisation of a mosaic add(12)(p13.3) with an inv dup(3)(q26.31->qter) detected in an autistic boy}}. {Mol Cytogenet};2009 (Aug 4);2(1):16.
ABSTRACT: BACKGROUND: Inverted duplications (inv dup) of a terminal chromosome region are a particular subset of rearrangements that often results in partial tetrasomy or partial trisomy when accompanied by a deleted chromosome. Associated mosaicism could be the consequence of a post-zygotic event or could result from the correction of a trisomic conception. Tetrasomies of distal segments of the chromosome 3q are rare genetic events and their phenotypic manifestations are diverse. To our knowledge, there are only 12 cases reported with partial 3q tetrasomy. Generally, individuals with this genomic imbalance present mild to severe developmental delay, facial dysmorphisms and skin pigmentary disorders. RESULTS: We present the results of the molecular cytogenetic characterization of an unbalanced mosaic karyotype consisting of mos 46,XY,add(12)(p13.3)[56]/46,XY[44] in a previously described 11 years old autistic boy, re-evaluated at adult age . The employment of fluorescence in situ hybridization (FISH) and multicolor banding (MCB) techniques identified the extra material on 12p to be derived from chromosome 3, defining the additional material on 12p as an inv dup(3)(qter->q26.3::q26.3->qter). Subsequently, array-based comparative genomic hybridization (aCGH) confirmed the breakpoint at 3q26.31, defining the extra material with a length of 24.92 Mb to be between 174.37 and 199.29 Mb. CONCLUSION: This is the thirteenth reported case of inversion-duplication 3q, being the first one described as an inv dup translocated onto a non-homologous chromosome. The mosaic terminal inv dup(3q) observed could be the result of three proposed alternative mechanisms. The most striking feature of this case is the autistic behavior of the proband, a characteristic not shared by any other patient with tetrasomy for 3q26.31->3qter. The present work further illustrates the advantages of the use of an integrative cytogenetic strategy, composed both by conventional and molecular techniques, on providing powerful information for an accurate diagnosis. This report also highlights a chromosome region potentially involved in autistic disorders.
3. Coben R, Myers TE. {{The Relative Efficacy of Connectivity Guided and Symptom Based EEG Biofeedback for Autistic Disorders}}. {Appl Psychophysiol Biofeedback};2009 (Aug 1)
Autism is a neurodevelopmental disorder characterized by deficits in communication, social interaction, and a limited range of interests with repetitive stereotypical behavior. Various abnormalities have been documented in the brains of individuals with autism, both anatomically and functionally. The connectivity theory of autism is a recently developed theory of the neurobiological cause of autisic symptoms. Different patterns of hyper- and hypo-connectivity have been identified with the use of quantitative electroencephalogray (QEEG), which may be amenable to neurofeedback. In this study, we compared the results of two published controlled studies examining the efficacy of neurofeedback in the treatment of autism. Specifically, we examined whether a symptom based approach or an assessment/connectivity guided based approach was more effective. Although both methods demonstrated significant improvement in symptoms of autism, connectivity guided neurofeedback demonstrated greater reduction on various subscales of the Autism Treatment Evaluation Checklist (ATEC). Furthermore, when individuals were matched for severity of symptoms, the amount of change per session was significantly higher in the Coben and Padolsky (J Neurother 11:5-23, 2007) study for all five measures of the ATEC. Our findings suggest that an approach guided by QEEG based connectivity assessment may be more efficacious in the treatment of autism. This permits the targeting and amelioration of abnormal connectivity patterns in the brains of people who are autistic.
4. Devarakonda KM, Lowthian D, Raghavendra T.{{ A case of Rett syndrome with reduced pain sensitivity}}. {Paediatr Anaesth};2009 (Jun);19(6):625-627.
5. Greimel E, Schulte-Ruther M, Kircher T, Kamp-Becker I, Remschmidt H, Fink GR, Herpertz-Dahlmann B, Konrad K. {{Neural mechanisms of empathy in adolescents with autism spectrum disorder and their fathers}}. {Neuroimage};2009 (Jul 30)
A deficit in empathy has been repeatedly described in individuals with autism spectrum disorder (ASD) and also, albeit less markedly, in their unaffected relatives. Here, we aimed to investigate the neural mechanisms of empathy in ASD, and to explore familial contributions to empathy correlates. Using functional magnetic resonance imaging, 15 boys with ASD, 11 fathers of adolescents with ASD, and two control groups comparable for age and IQ (n=15 typically developing boys and their fathers (n=9)) were investigated during an empathy task. Emotional faces were presented and participants were either asked to infer the emotional state from the face (other-task) or to judge their own emotional response to the face (self-task). When attributing emotions to self and other, the ASD group showed diminished fusiform gyrus activation compared to controls. Neural activity in the fusiform gyrus was inversely related to social deficits in ASD subjects. Moreover, when ASD subjects inferred their own emotional response to faces, they showed less congruent reactions and inferior frontal gyrus activity was decreased. Although fathers of ASD children scored higher on a self-rating scale for autistic symptoms compared to control fathers, their task performance was unimpaired. However, neurally, fathers of affected children also showed reduced fusiform gyrus activation when inferring others’ emotions. Shared abnormalities in fusiform gyrus activation in affected adolescents and first-degree relatives suggest that this dysfunction constitutes a fundamental deviation in ASD. Moreover, the findings provide evidence that both aberrant neural face and mirroring mechanisms are implicated in empathy impairments in ASD.
6. Guhathakurta S, Singh AS, Sinha S, Chatterjee A, Ahmed S, Ghosh S, Usha R. {{Analysis of serotonin receptor 2A gene (HTR2A): Association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes}}. {Neurochem Int};2009 (Jul 30)
Several studies suggest involvement of serotoninergic system in the pathophysiology of Autism Spectrum Disorder (ASD). The 5-HT receptor binding studies using (3)H-lysergic acid diethylamide ((3)H-LSD) and linkage analysis provided evidences to consider HTR2A as a potential candidate gene for ASD. The three SNPs, -1438A/G (rs6311), 102T/C (rs6313) and 1354C/T (rs6314) of HTR2A have been well studied in the etiology of various neuropsychiatric disorders. But studies on association of this gene with ASD are limited to two reports from American and Korean populations. Additionally there are reports which demonstrated paternal imprinting of HTR2A with expression from only one allele. So far no reports are available on HTR2A and its association with any neuropsychiatric disorders from Indian population. Therefore, the present study investigates association of the above mentioned three markers of HTR2A with ASD in Indian population using population and family-based approaches. The study also deals with allelic expression pattern of HTR2A in Peripheral Blood Leukocytes (PBLs) to understand the parental imprinting status. The genotyping analyses were carried out for probands, parents and controls. The subsequent association analyses did not show association of these markers with ASD. So, HTR2A is unlikely to be a genetic marker for ASD in Indian population. The expression analyses showed absence of monoallelic expression, suggesting lack of parental imprinting of HTR2A gene. However, we noticed methylation of the CpG sites at -1438A/G and 102T/C loci of HTR2A gene. Further bioinformatics analysis revealed absence of CpG islands in the promoter of the gene supporting biallelic expression pattern of HTR2A in PBLs.
7. Gutierrez RC, Hung J, Zhang Y, Kertesz AC, Espina FJ, Colicos MA. {{Altered synchrony and connectivity in neuronal networks expressing an autism-related mutation of neuroligin 3}}. {Neuroscience};2009 (Aug 4);162(1):208-221.
The neuroligin (NL) gene family codes for brain specific cell adhesion molecules that play an important role in synaptic connectivity. Recent studies have identified NL mutations linked to patients with autism spectrum disorders (ASD). Cognitive deficits seen in autistic patients are hypothesized to arise from altered synchronicity both within and between brain regions. Here we show how the expression of autism-associated neuroligin mutation R471C-NL3 affects synchrony in dissociated cultures of rat hippocampal neurons. Spontaneous network activity patterns of cultures expressing wild type and mutant NL3 were measured by optical techniques. Firing events were quantified and compared by cross-correlation analysis. Our results suggest that NL3 overexpression enhances synchrony of spontaneous activity patterns, however, this ability is reduced with the R471C-NL3 mutation. We investigated the structural basis of this phenomenon using fractal dimension analysis to characterize the arrangement of axon trajectories. R471C-NL3 cultures were associated with lower fractal dimensions and higher lacunarity values, indicating a decrease in the complexity of axonal architecture. Transfection of R471C-NL3 into a subpopulation of cells in a network resulted in neuronal degeneration. This degeneration likely affected the inhibitory population of neurons, as there were half as many (P<0.01, n=12) glutamate decarboxylase (GAD) 65 expressing cells in R471C-NL3 cultures compared to wild type NL3 and control cultures. Electrophysiological recordings showed a reduction of inhibitory activity in networks carrying the mutation in comparison to networks overexpressing wild-type NL3. Together, these data support the hypothesis that the autism-associated NL3 mutation affects information processing in neuronal networks by altering network architecture and synchrony.
8. Jones TB, Bandettini PA, Kenworthy L, Case LK, Milleville SC, Martin A, Birn RM. {{Sources of group differences in functional connectivity: An investigation applied to autism spectrum disorder}}. {Neuroimage};2009 (Jul 29)
An increasing number of fMRI studies are using the correlation of low-frequency fluctuations between brain regions, believed to reflect synchronized variations in neuronal activity, to infer « functional connectivity ». In studies of autism spectrum disorder (ASD), decreases in this measure of connectivity have been found by focusing on the response to task modulation, by using only the rest periods, or by analyzing purely resting-state data. This difference in connectivity, however, could result from a number of different mechanisms – differences in noise, task-related fluctuations, task performance, or spontaneous neuronal activity. In this study, we investigate the difference in functional connectivity between adolescents with high-functioning ASD and typically developing control subjects by examining the residual fluctuations occurring on top of the fMRI response to an overt verbal fluency task. We find decreased correlations of these residuals (a decreased « connectivity ») in ASD subjects. Furthermore, we find that this decrease was not due to task-related effects, block-to-block variations in task performance, or increased noise, and the difference was greatest when primarily rest periods are considered. These findings suggest that the estimate of disrupted functional connectivity in ASD is likely driven by differences in task-unrelated neuronal fluctuations.
9. Oblak A, Gibbs TT, Blatt GJ. {{Decreased GABA(A) receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism}}. {Autism Res};2009 (Jul 31)
The anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio-emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and gamma-amino-butyric acid (GABA) system may be affected in autism. The benzodiazepine binding site on the GABA(A) receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple-concentration ligand-binding study utilized (3)H-muscimol and (3)H-flunitrazepam to determine the number (B(max)), binding affinity (K(d)), and distribution of GABA(A) receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABA(A) receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4%) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABA(A) receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio-emotional behaviors in autism.
10. Pampanos A, Volaki K, Kanavakis E, Papandreou O, Youroukos S, Thomaidis L, Karkelis S, Tzetis M, Kitsiou-Tzeli S. A {{Substitution Involving the NLGN4 Gene Associated with Autistic Behavior in the Greek Population}}. {Genet Test Mol Biomarkers};2009 (Aug 2)
Autism is a neurodevelopmental disorder characterized by clinical, etiologic, and genetic heterogeneity. During the last decade, predisposing genes and genetic loci were under investigation. Recently, mutations in two X-linked neuroligin genes, neuroligin 3 (NLGN3) and neuroligin 4 (NLGN4), have been implicated in the pathogenesis of autism. In our ongoing survey, we screened 169 patients with autism for mutations linked with autism. In the preliminary study of specific exons of NLGN3 and NLGN4 genes, we identified the p.K378R substitution (c.1597 A > G) in exon 5 of the NLGN4 gene in a patient who was found to have mild autism and normal IQ at 3 years of age. The same mutation has previously been found in a patient with autism. It is important that, for the first time, a specific mutation in neuroligins is confirmed in a molecular screen in another homogeneous ethnic population. This finding further contributes to consideration of neuroligins as probable candidate genes for future molecular genetic studies, suggesting that a defect of synaptogenesis may predispose to autism.
11. Schwartz C, Bente G, Gawronski A, Schilbach L, Vogeley K. {{Responses to Nonverbal Behaviour of Dynamic Virtual Characters in High-Functioning Autism}}. {J Autism Dev Disord};2009 (Aug 4)
We investigated feelings of involvement evoked by nonverbal behaviour of dynamic virtual characters in 20 adults with high-functioning autism (HFA) and high IQ as well as 20 IQ-matched control subjects. The effects of diagnostic group showed that subjects with autism experienced less « contact » and « urge » to establish contact across conditions and less « interest » than controls in a condition with meaningful facial expressions. Moreover, the analyses within groups revealed that nonverbal behaviour had less influence on feelings in HFA subjects. In conclusion, disturbances of HFA subjects in experiencing involvement in social encounters with virtual characters displaying nonverbal behaviour do not extend to all kinds of feelings, suggesting different pathways in the ascription of involvement in social situations.
12. Strathearn L. {{The elusive etiology of autism: nature and nurture?}} {Front Behav Neurosci};2009;3:11.
