1. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah IN, Van de Water J. {{Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders}}. {J Neuroimmunol};2010 (Nov 20)
A role for immune dysfunction has been suggested in autism spectrum disorders (ASD). Elevated levels of chemokines have been detected in the brain and CSF of individuals with ASD but, to date, no study has examined chemokine levels in the plasma of children with this disorder. In the current study, we determined whether there were differential profiles of chemokines in the plasma of children with ASD compared to age-matched typically developing controls and children with developmental disabilities other than ASD. Increased MCP-1, RANTES and eotaxin levels were observed in ASD children compared with both control groups (p<0.03), and increased chemokine production was associated with higher aberrant behavior scores and more impaired developmental and adaptive function.. Elevated MCP-1, RANTES and eotaxin in some ASD children and their association with more impaired behaviors may have etiological significance. Chemokines and their receptors might provide unique targets for future therapies in ASD.
2. Baron-Cohen S. {{Empathizing, systemizing, and the extreme male brain theory of autism}}. {Prog Brain Res};2010;186:167-175.
Females in the general population on average have a stronger drive to empathize, and males in the general population on average have a stronger drive to systemize. Evidence related to these claims is reviewed. People with autism spectrum conditions have below average empathy alongside intact or even above average interest in systems. As such, they can be conceptualized as an extreme of the typical male brain.
3. Burnette CP, Henderson HA, Inge AP, Zahka NE, Schwartz CB, Mundy PC. {{Anterior EEG Asymmetry and the Modifier Model of Autism}}. {J Autism Dev Disord};2010 (Nov 24)
Individual differences in the expression of autism complicate research on the nature and treatment of this disorder. In the Modifier Model of Autism (Mundy et al. 2007), we proposed that individual differences in autism may result not only from syndrome specific causal processes, but also from variability in generic, non-syndrome specific modifier processes that affect the social and emotional development of all people. One study supporting this model found that measures of resting anterior EEG asymmetry, a measure reflecting complex brain processes associated with generic individual differences in approach and avoidance motivation, may help explain differences in the expression of autism in children without intellectual disabilities (Sutton et al. 2005). In the current study, we partially replicated the observation that children with autism who exhibited a pattern of left frontal EEG asymmetry tended to display milder levels of social symptoms, although in the current sample this pattern applied only to HFA children with relatively lower verbal IQs. New observations indicated that left frontal EEG asymmetry was also associated with retrospective parent reports of significantly later age of onset of symptoms, but also higher levels of self-reported outward expressions of anger as well as symptoms of obsessive compulsive disorder in school-age higher functioning children with ASD. Therefore, the results of this study provide a new and fully independent set of observations, which indicate that individual differences in anterior EEG asymmetry may significantly moderate the expression and developmental course of autism. This observation may have clinical implications for identifying meaningful diagnostic sub-groups among children with autism.
4. Costa S, Santos C, Soares F, Ferreira M, Moreira F. {{Promoting interaction amongst autistic adolescents using robots}}. {Conf Proc IEEE Eng Med Biol Soc};2010;1:3856-3859.
Most autistic people present some difficulties in developing social behavior, living in their own world. The intent of this study is to improve the social life of adolescents with both autism and mental impairment, with a main focus on promoting their social interaction and communication. An experiment designed to call for the adolescents’ attention and enforce their collaboration is described; in it a LEGO MindStorm robot behaves as a mediator/promotor of this interaction. Further, sensory motor coordination and accuracy skills of the adolescents are also slightly explored. Four scenarios were envisaged. Results are described showing the outcomes of the experiment.
5. Filges I, Rothlisberger B, Blattner A, Boesch N, Demougin P, Wenzel F, Huber A, Heinimann K, Weber P, Miny P. {{Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism}}. {Clin Genet};2010 (Nov 4)
Filges I, Rothlisberger B, Blattner A, Boesch N, Demougin P, Wenzel F, Huber AR, Heinimann K, Weber P, Miny P. Deletion in Xp22.11: PTCHD1 is a candidate gene for X-linked intellectual disability with or without autism. Submicroscopic chromosomal anomalies play an important role in the aetiology of intellectual disability (ID) and have been shown to account for up to 10% of non-syndromic forms. We present a family with two affected boys compatible with X-linked inheritance of a phenotype of severe neurodevelopmental disorder cosegregating with a deletion in Xp22.11 exclusively containing the PTCHD1 gene. Although the exact function of this gene is unknown to date, the structural overlap of its encoded patched domain-containing protein 1, the transmembrane protein involved in the sonic hedgehog pathway, and its expression in human cortex and cerebellum as well as in mice and drosophila brain suggests a causative role of its nullisomy in the developmental phenotype of our family. Our findings support the recent notions that PTCHD1 may play a role in X-linked intellectual disability (XLID) and autism disorders.
6. Freeth M, Foulsham T, Chapman P. {{The influence of visual saliency on fixation patterns in individuals with Autism Spectrum Disorders}}. {Neuropsychologia};2010 (Nov 17)
It is widely reported that individuals with Autism Spectrum Disorders (ASD) direct their attention in an atypical manner. When viewing complex scenes, typically developing individuals look at social aspects of scenes more rapidly than individuals with ASD. In the absence of a strong drive to extract social information, is something else capturing attention in these initial fixations, such as visually salient features? Twenty four high-functioning adolescents with ASD and 24 typically developing matched control participants viewed a series of indoor and outdoor scenes while their eye movements were tracked. Participants in both groups were more likely to fixate on salient regions in the first five fixations than later in viewing. Peak saliency at fixation occurred at fixation two for the typically developing participants but at fixation three for ASD participants. This difference was driven by typically developing participants looking at heads earlier than ASD participants – which are often visually salient. No differences between groups were observed for images in which the heads were not salient. We can therefore conclude that visual saliency impacts fixation location in a similar manner in individuals with ASD and those with typical development. It was found that social features in scenes (heads) captured attention much more than visually salient features, even in individuals with ASD.
7. Gargaro BA, Rinehart NJ, Bradshaw JL, Tonge BJ, Sheppard DM. {{Autism and ADHD: How far have we come in the comorbidity debate?}}. {Neurosci Biobehav Rev};2010 (Nov 18)
The potential for the coexistence of the developmental disorders autism and attention-deficit/hyperactivity disorder (ADHD) in any one individual has for a long time been a contentious issue. While from a neurobiological perspective it is possible, and even highly likely, that ADHD and autism might clinically co-exist, our major diagnostic classification systems (DSM-IV-TR and ICD-10) currently preclude such a dual-diagnosis. The aim of the current review is to summarise current diagnostic criteria and treatment strategies for the two disorders, relevant theories of developmental dysfunction, and update the state of the debate regarding comorbidity. Evidence from clinical, neuroimaging and neuropsychological domains is considered, and similarities and differences between the two disorders are identified. Suggestions for future research into the comorbid profiles of these disorders are proposed, with a strong emphasis placed on the neuropsychological assessment of executive functioning as a potentially useful tool for both identifying similarities, and differentiating the disorders.
8. Grzadzinski R, Di Martino A, Brady E, Mairena MA, O’Neale M, Petkova E, Lord C, Castellanos FX. {{Examining Autistic Traits in Children with ADHD: Does the Autism Spectrum Extend to ADHD?}}. {J Autism Dev Disord};2010 (Nov 25)
We examined to what extent increased parent reports of autistic traits in some children with Attention Deficit Hyperactivity Disorder (ADHD) are the result of ADHD-related symptoms or qualitatively similar to the core characteristics of autism spectrum disorders (ASD). Results confirm the presence of a subgroup of children with ADHD and elevated ratings of core ASD traits (ADHD(+)) not accounted for by ADHD or behavioral symptoms. Further, analyses revealed greater oppositional behaviors, but not greater ADHD severity or anxiety, in the ADHD(+) subgroup compared to those with ADHD only. These results highlight the importance of specifically examining autistic traits in children with ADHD for better characterization in studies of the underlying physiopathology and treatment.
9. Hamilton SM, Spencer CM, Harrison WR, Yuva-Paylor LA, Graham DF, Daza RA, Hevner RF, Overbeek PA, Paylor R. {{Multiple autism-like behaviors in a novel transgenic mouse model}}. {Behav Brain Res};2010 (Nov 17)
Autism spectrum disorder (ASD) diagnoses are behaviorally based with no defined universal biomarkers, occur at a 1:110 ratio in the population, and predominantly affect males compared to females at approximately a 4:1 ratio. One approach to investigate and identify causes of ASD is to use organisms that display abnormal behavioral responses that model ASD-related impairments. This study describes a novel transgenic mouse, MALTT, which was generated using a forward genetics approach. It was determined that the transgene integrated within a non-coding region on the X chromosome. The MALTT line exhibited a complete repertoire of ASD-like behavioral deficits in all three domains required for an ASD diagnosis: reciprocal social interaction, communication, and repetitive or inflexible behaviors. Specifically, MALTT male mice showed deficits in social interaction and interest, abnormalities in pup and juvenile ultrasonic vocalization communications, and exhibited a repetitive stereotypy. Abnormalities were also observed in the domain of sensory function, a secondary phenotype prevalently associated with ASD. Mapping and expression studies suggested that the Fam46 gene family may be linked to the observed ASD-related behaviors. The MALTT line provides a unique genetic model for examining the underlying biological mechanisms involved in ASD-related behaviors.
10. Joosten AV, Bundy AC. {{Sensory processing and stereotypical and repetitive behaviour in children with autism and intellectual disability}}. {Aust Occup Ther J};2010 (Dec);57(6):366-372.
Background: Sensory processing disorders have been linked to stereotypical behaviours in children with intellectual disability (ID) and autism spectrum disorders (ASD) and to anxiety in children with ASD. In earlier phases of this study with the same participants, we found that those with both ASD and ID were more motivated than those with ID alone to engage in stereotypical behaviour to alleviate anxiety. In this phase, we confirmed that children with both ASD and ID and those with ID alone process sensation differently than typically developing children. We asked: Do the sensory processing difficulties of children with ASD and ID differ significantly from those of children with ID alone in a way that would help explain the increased anxiety of the former group? Method: Parents of children with ASD and ID (n = 29; mean age 9.7 years) and with ID alone (n = 23; mean age 9.5 years) completed a Sensory Profile (SP) to provide information about their children’s sensory processing abilities. SP quadrant scores for each group were compared with each other and with the published norms of typically developing children. Results: Children with ASD and ID and with ID alone processed sensory information differently than typically developing children (P = 0.0001;d = > 2.00). Children with both ASD and ID were significantly more sensitive (P = 0.007;d = 0.70) and avoidant (P < 0.05;d = 0.47) than the children with ID alone. Conclusion: We conclude that increased sensitivity and the tendency to avoid sensation may help explain anxiety in children with autism.
11. Khanna R, Madhavan SS, Smith MJ, Patrick JH, Tworek C, Becker-Cottrill B. {{Assessment of Health-Related Quality of Life Among Primary Caregivers of Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2010 (Nov 20)
The impact of caring for a child with autism on caregivers’ health-related quality of life (HRQOL) is not fully understood. The objective of this study was to compare the HRQOL scores of caregivers of children with autism to those of the general US population and to identify the factors that influence HRQOL. Caregivers of children with autism had lower HRQOL scores than the general population. Care recipient level of functional impairment, social support, use of maladaptive coping, and burden influenced caregiver mental HRQOL. Care recipient extent of behavioral problems and social support influenced caregiver physical HRQOL. Findings emphasize the use of multi-pronged intervention approach that incorporates components aimed at improving family functioning, increasing support services, and assisting caregivers in developing healthy coping skills.
12. Kunda M, Goel AK. {{Thinking in Pictures as a Cognitive Account of Autism}}. {J Autism Dev Disord};2010 (Nov 20)
We analyze the hypothesis that some individuals on the autism spectrum may use visual mental representations and processes to perform certain tasks that typically developing individuals perform verbally. We present a framework for interpreting empirical evidence related to this « Thinking in Pictures » hypothesis and then provide comprehensive reviews of data from several different cognitive tasks, including the n-back task, serial recall, dual task studies, Raven’s Progressive Matrices, semantic processing, false belief tasks, visual search, spatial recall, and visual recall. We also discuss the relationships between the Thinking in Pictures hypothesis and other cognitive theories of autism including Mindblindness, Executive Dysfunction, Weak Central Coherence, and Enhanced Perceptual Functioning.
13. Napolioni V, Lombardi F, Sacco R, Curatolo P, Manzi B, Alessandrelli R, Militerni R, Bravaccio C, Lenti C, Saccani M, Schneider C, Melmed R, Pascucci T, Puglisi-Allegra S, Reichelt KL, Rousseau F, Lewin P, Persico AM. {{Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes}}. {Eur J Hum Genet};2010 (Nov 24)
The integrin-beta 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are significantly associated with autism (HBAT, global P=0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P=0.005; odds ratio (OR)=2.000), at the expense of haplotype H1, which is under-transmitted (HBAT P=0.018; OR=0.725). These two common haplotypes differ only at rs12603582 located in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses. Interestingly, rs12603582 is strongly associated with pre-term delivery in our ASD patients (P=0.008). On the other hand, it is SNP rs2317385, located at the 5′ end of the gene, that significantly affects 5-HT blood levels (Mann-Whitney U-test, P=0.001; multiple regression analysis, P=0.010). No gene-gene interaction between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a significant association between a common ITGB3 haplotype and ASD. Distinct markers, located toward the 5′ and 3′ ends of the gene, seemingly modulate 5-HT blood levels and autism liability, respectively. Our results also raise interest into ITGB3 influences on feto-maternal immune interactions in autism.European Journal of Human Genetics advance online publication, 24 November 2010; doi:10.1038/ejhg.2010.180.
14. Nappo S. {{A retrospective observational study of enuresis, daytime voiding symptoms, and response to medical therapy in children with attention deficit hyperactivity disorder and autism spectrum disorder}}. {J Pediatr Urol};2010 (Nov 20)
15. Percy AK, Neul JL, Glaze DG, Motil KJ, Skinner SA, Khwaja O, Lee HS, Lane JB, Barrish JO, Annese F, McNair L, Graham J, Barnes K. {{Rett syndrome diagnostic criteria: Lessons from the Natural History Study}}. {Ann Neurol};2010 (Nov 22)
Analysis of 819 participants enrolled in the Rett syndrome (RTT) Natural History Study validates recently revised diagnostic criteria. 765 females fulfilled 2002 consensus criteria for classic (653/85.4%) or variant (112/14.6%) RTT. All participants classified as classic RTT fulfilled each revised main criterion; supportive criteria were not uniformly present. All variant RTT participants met at least 3 of 6 main criteria in the 2002, 2 of 4 main criteria in the current format, and 5 of 11 supportive criteria in both. This analysis underscores the critical role of main criteria for classic RTT; variant RTT requires both main and supportive criteria. Ann Neurol 2010.
16. Pollonini L, Patidar U, Situ N, Rezaie R, Papanicolaou AC, Zouridakis G. {{Functional connectivity networks in the autistic and healthy brain assessed using Granger causality}}. {Conf Proc IEEE Eng Med Biol Soc};2010;1:1730-1733.
In this study, we analyze brain connectivity based on Granger causality computed from magnetoencephalographic (MEG) activity obtained at the resting state in eight autistic and eight normal subjects along with measures of network connectivity derived from graph theory in an attempt to understand how communication in a human brain network is affected by autism. A connectivity matrix was computed for each subject individually and then group templates were estimated by averaging all matrices in each group. Furthermore, we performed classification of the subjects using support vector machines and Fisher’s criterion to rank the features and identify the best subset for maximum separation of the groups. Our results show that a combined model based on connectivity matrices and graph theory measures can provide 87.5% accuracy in separating the two groups. These findings suggest that analysis of functional connectivity patterns may provide a valuable method for the early detection of autism.
17. Ramachandran VS, Seckel EL. {{Synchronized dance therapy to stimulate mirror neurons in autism}}. {Med Hypotheses};2010 (Nov 20)
18. Shukla DK, Keehn B, Lincoln AJ, Muller RA. {{White matter compromise of callosal and subcortical fiber tracts in children with autism spectrum disorder: a diffusion tensor imaging study}}. {J Am Acad Child Adolesc Psychiatry};2010 (Dec);49(12):1269-1278 e1262.
OBJECTIVE: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle cerebellar peduncle in children with ASD and typically developing (TD) children. METHOD: DTI data were obtained from 26 children with ASD and 24 matched TD children. Fractional anisotropy (FA), mean diffusivity (MD), and axial and radial diffusion were calculated for the whole brain, the genu, body, and splenium of the corpus callosum, the genu and anterior and posterior limbs of the internal capsule, and the middle cerebellar peduncle. RESULTS: Children with ASD had reduced FA and increased radial diffusion for whole-brain white matter and all three segments of the corpus callosum and internal capsule, compared with those in TD children. Increased MD was found for the whole brain and for anterior and posterior limbs of the internal capsule. Reduced axial diffusion was found for the body of corpus callosum. Reduced FA was also found for the middle cerebellar peduncle. CONCLUSIONS: Our findings suggest widespread white matter compromise in children with ASD. Abnormalities in the corpus callosum indicate impaired interhemispheric transfer. Results for the internal capsule and middle cerebellar peduncle add to the currently limited DTI evidence on subcortico-cortical tracts in ASD. The robust impairment found in all three segments of the internal capsule is consistent with studies documenting impairment of elementary sensorimotor function in ASD.
19. Su H, Dickstein-Fischer L, Harrington K, Fu Q, Lu W, Huang H, Cole G, Fischer GS. {{Cable-driven elastic parallel humanoid head with face tracking for Autism Spectrum Disorder interventions}}. {Conf Proc IEEE Eng Med Biol Soc};2010;1:467-470.
This paper presents the development of new prismatic actuation approach and its application in human-safe humanoid head design. To reduce actuator output impedance and mitigate unexpected external shock, the prismatic actuation method uses cables to drive a piston with preloaded spring. By leveraging the advantages of parallel manipulator and cable-driven mechanism, the developed neck has a parallel manipulator embodiment with two cable-driven limbs embedded with preloaded springs and one passive limb. The eye mechanism is adapted for low-cost webcam with succinct « ball-in-socket » structure. Based on human head anatomy and biomimetics, the neck has 3 degree of freedom (DOF) motion: pan, tilt and one decoupled roll while each eye has independent pan and synchronous tilt motion (3 DOF eyes). A Kalman filter based face tracking algorithm is implemented to interact with the human. This neck and eye structure is translatable to other human-safe humanoid robots. The robot’s appearance reflects a non-threatening image of a penguin, which can be translated into a possible therapeutic intervention for children with Autism Spectrum Disorders.
20. Watanabe Y, Yano S, Niihori T, Aoki Y, Matsubara Y, Yoshino M, Matsuishi T. {{A familial case of LEOPARD syndrome associated with a high-functioning autism spectrum disorder}}. {Brain Dev};2010 (Nov 17)
A connection between LEOPARD syndrome (a rare autosomal dominant disorder) and autism spectrum disorders (ASDs) may exist. Of four related individuals (father and three sons) with LEOPARD syndrome, all patients exhibited clinical symptoms consistent with ASDs. Findings included aggressive behavior and impairment of social interaction, communication, and range of interests. The coexistence of LEOPARD syndrome and ASDs in the related individuals may be an incidental familial event or indicative that ASDs is associated with LEOPARD syndrome. There have been no other independent reports of the association of LEOPARD syndrome and ASDs. Molecular and biochemical mechanisms that may suggest a connection between LEOPARD syndrome and ASDs are discussed.
