1. Amaral D, Rogers SJ, Baron-Cohen S, Bourgeron T, Caffo E, Fombonne E, Fuentes J, Howlin P, Rutter M, Klin A, Volkmar F, Lord C, Minshew N, Nardocci F, Rizzolatti G, Russo S, Scifo R, van der Gaag RJ. {{Against le packing: a consensus statement}}. {J Am Acad Child Adolesc Psychiatry};2011 (Feb);50(2):191-192.
2. Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Ted Brown W, Chauhan V. {{Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism}}. {J Neurochem};2011 (Jan 19)
Mitochondria play important roles in generation of free radicals, ATP formation, and in apoptosis. We studied the levels of mitochondrial electron transport chain (ETC) complexes, i.e., complexes I, II, III, IV, and V, in brain tissue samples from the cerebellum and the frontal, parietal, occipital, and temporal cortices of subjects with autism and age-matched control subjects. The subjects were divided into two groups according to their ages: Group A (children, ages 4-10 years) and Group B (adults, ages 14-39 years). In Group A, we observed significantly lower levels of complexes III and V in the cerebellum (p < 0.05), of complex I in the frontal cortex (p < 0.05), and of complexes II (p < 0.01), III (p < 0.01), and V (p < 0.05) in the temporal cortex of children with autism as compared to age-matched control subjects, while none of the five ETC complexes was affected in the parietal and occipital cortices in subjects with autism. In the cerebellum and temporal cortex, no overlap was observed in the levels of these ETC complexes between subjects with autism and control subjects. In the frontal cortex of Group A, a lower level of ETC complexes was observed in a subset of autism cases, i.e., 60% (3/5) for complexes I, II, and V, and 40% (2/5) for complexes III and IV. A striking observation was that the levels of ETC complexes were similar in adult subjects with autism and control subjects (Group B). A significant increase in the levels of lipid hydroperoxides, an oxidative stress marker, was also observed in the cerebellum and temporal cortex in the children with autism. These results suggest that the expression of ETC complexes is decreased in the cerebellum and the frontal and temporal regions of the brain in children with autism, which may lead to abnormal energy metabolism and oxidative stress. The deficits observed in the levels of ETC complexes in children with autism may readjust to normal levels by adulthood.
3. Ghaziuddin M. {{Asperger Disorder in the DSM-V: Sacrificing Utility for Validity}}. {J Am Acad Child Adolesc Psychiatry};2011 (Feb);50(2):192-193.
4. Hussman JP, Chung RH, Griswold AJ, Jaworkski JM, Salyakina D, Ma D, Konidari I, Whitehead PL, Vance JM, Martin ER, Cuccaro ML, Gilbert JR, Haines JL, Pericak-Vance MA. {{A noise-reduction GWAS analysis implicates altered regulation of neurite outgrowth and guidance in autism}}. {Mol Autism};2011 (Jan 19);2(1):1.
ABSTRACT: BACKGROUND: Genome-wide Association Studies (GWAS) have proved invaluable for the identification of disease susceptibility genes. However, the prioritization of candidate genes and regions for follow-up studies often proves difficult due to false-positive associations caused by statistical noise and multiple-testing. In order to address this issue, we propose the novel GWAS noise reduction (GWAS-NR) method as a way to increase the power to detect true associations in GWAS, particularly in complex diseases such as autism. METHODS: GWAS-NR utilizes a linear filter to identify genomic regions demonstrating correlation among association signals in multiple datasets. We used computer simulations to assess the ability of GWAS-NR to detect association against the commonly used joint analysis and Fisher’s methods. Furthermore, we applied GWAS-NR to a family-based autism GWAS of 597 families and a second existing autism GWAS of 696 families from the Autism Genetic Resource Exchange (AGRE) to arrive at a compendium of autism candidate genes. These genes were manually annotated and classified by a literature review and functional grouping in order to reveal biological pathways which might contribute to autism aetiology. RESULTS: Computer simulations indicate that GWAS-NR achieves a significantly higher classification rate for true positive association signals than either the joint analysis or Fisher’s methods and that it can also achieve this when there is imperfect marker overlap across datasets or when the closest disease-related polymorphism is not directly typed. In two autism datasets, GWAS-NR analysis resulted in 1535 significant linkage disequilibrium (LD) blocks overlapping 431 unique reference sequencing (RefSeq) genes. Moreover, we identified the nearest RefSeq gene to the non-gene overlapping LD blocks, producing a final candidate set of 860 genes. Functional categorization of these implicated genes indicates that a significant proportion of them cooperate in a coherent pathway that regulates the directional protrusion of axons and dendrites to their appropriate synaptic targets. CONCLUSIONS: As statistical noise is likely to particularly affect studies of complex disorders, where genetic heterogeneity or interaction between genes may confound the ability to detect association, GWAS-NR offers a powerful method for prioritizing regions for follow-up studies. Applying this method to autism datasets, GWAS-NR analysis indicates that a large subset of genes involved in the outgrowth and guidance of axons and dendrites is implicated in the aetiology of autism.
5. O’Hearn K, Lakusta L, Schroer E, Minshew N, Luna B. {{Deficits in adults with autism spectrum disorders when processing multiple objects in dynamic scenes}}. {Autism Res};2011 (Jan 19)
People with autism spectrum disorders (ASD) process visual information in a manner that is distinct from typically developing individuals. They may be less sensitive to people’s goals and, more generally, focus on visual details instead of the entire scene. To examine these differences, people with and without ASD were asked to detect changes in dynamic scenes with multiple elements. Participants viewed a brief video of a person or an inanimate object (the « figure ») moving from one object to another; after a delay, they reported whether a second video was the same or different. Possible changes included the figure, the object the figure was moving from, or the object the figure was moving toward (the « goal »). We hypothesized that individuals with ASD would be less sensitive to changes in scenes with people, particularly elements that might be the person’s goal. Alternately, people with ASD might attend to fewer elements regardless of whether the scene included a person. Our results indicate that, like controls, people with ASD noticed a change in the « goal » object at the end of a person’s movement more often than the object at the start. However, the group with ASD did not undergo the developmental improvement that was evident typically when detecting changes in both the start and end objects. This atypical development led to deficits in adults with ASD that were not specific to scenes with people or to « goals. » Improvements in visual processing that underlie mature representation of scenes may not occur in ASD, suggesting that late developing brain processes are affected.
6. Pelphrey KA, Shultz S, Hudac CM, Vander Wyk BC. {{Research Review: Constraining heterogeneity: the social brain and its development in autism spectrum disorder}}. {J Child Psychol Psychiatry};2011 (Jan 19)
The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved in social information processing (i.e., the ‘social brain’). From this early and primary disruption, abnormal brain development is canalized because the individual with an ASD must develop in a highly social world without the specialized neural systems that would ordinarily allow him or her to partake in the fabric of social life, which is woven from the thread of opportunities for social reciprocity and the tools of social engagement. This brain canalization gives rise to other characteristic behavioral deficits in ASD including deficits in communication, restricted interests, and repetitive behaviors. We propose that focused efforts to explore the brain mechanisms underlying the core, pathognomic deficits in the development of mechanisms for social engagement in ASD will greatly elucidate our understanding and treatment of this complex, devastating family of neurodevelopmental disorders. In particular, developmental studies (i.e., longitudinal studies of young children with and without ASD, as well as infants at increased risk for being identified with ASD) of the neural circuitry supporting key aspects of social information processing are likely to provide important insights into the underlying components of the full-syndrome of ASD. These studies could also contribute to the identification of developmental brain endophenotypes to facilitate genetic studies. The potential for this kind of approach is illustrated via examples of functional neuroimaging research from our own laboratory implicating the posterior superior temporal sulcus (STS) as a key player in the set of neural structures giving rise to ASD.
7. Samyn V, Roeyers H, Bijttebier P. {{Effortful control in typically developing boys and in boys with ADHD or autism spectrum disorder}}. {Res Dev Disabil};2011 (Jan 19)
Despite increased interest in the role of effortful control (EC) in developmental disorders, few studies have focused on EC in autism spectrum disorders (ASD) and no study so far has directly compared children with ASD and children with ADHD. A first aim of this study was to investigate whether typically developing (TD) boys, boys with ADHD and boys with ASD can be differentiated based on EC levels. A second aim was to evaluate the relationship between EC and symptoms of ADHD and ASD. We assessed EC in 27 TD boys, 27 boys with ADHD and 27 boys with ASD (age 10-15) using different EC questionnaires. Clinical groups scored lower than the TD group on all EC total scales, but could only be differentiated from each other by means of self-reported persistence, impulsivity and activation control. Our data suggest that although EC is useful in differentiating TD boys from clinical groups, it is less efficient in distinguishing ADHD from ASD. Also, results suggest that EC plays a role in the manifestation of symptoms of both ADHD and ASD and that high levels of EC enable children to function more adequate in daily situations.
8. Sipes M, Matson JL, Horovitz M, Shoemaker M. {{The relationship between autism spectrum disorders and symptoms of conduct problems: The moderating effect of communication}}. {Dev Neurorehabil};2011;14(1):54-59.
Objective: To examine the relationship between ASD diagnosis (i.e. Autism, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) and atypical developing control) and tantrum/conduct symptoms in infants and toddlers. Then examine the moderating role of communication. Design: Analysis of Covariance was conducted for study 1 followed by hierarchical regression analyses for study 2. Methods: The Baby and Infant Screen for Children with aUtIsm Traits, Part 2 was administered to the caregivers of 774 infants and toddlers. Results: Those with autism exhibited the greatest tantrum/conduct symptoms followed by those with PDD-NOS and then atypical controls, F(3, 771) = 94.42, p = 0.003. Communication was not a significant moderator. Conclusions: Those with Autistic Disorder exhibited greater symptoms of tantrum/conduct problems, which is consistent with previous research. It seems that the relationship with communication as a moderator may differ in young children as their language skills are still in the early stages of development.
9. Tesink CM, Buitelaar JK, Petersson KM, Gaag RJ, Teunisse JP, Hagoort P. {{Neural correlates of language comprehension in autism spectrum disorders: When language conflicts with world knowledge}}. {Neuropsychologia};2011 (Jan 14)
In individuals with ASD, difficulties with language comprehension are most evident when higher-level semantic-pragmatic language processing is required, for instance when context has to be used to interpret the meaning of an utterance. Until now, it is unclear at what level of processing and for what type of context these difficulties in language comprehension occur. Therefore, in the current fMRI study, we investigated the neural correlates of the integration of contextual information during auditory language comprehension in 24 adults with ASD and 24 matched control participants. Different levels of context processing were manipulated by using spoken sentences that were correct or contained either a semantic or world knowledge anomaly. Our findings demonstrated significant differences between the groups in inferior frontal cortex that were only present for sentences with a world knowledge anomaly. Relative to the ASD group, the control group showed significantly increased activation in left inferior frontal gyrus (LIFG) for sentences with a world knowledge anomaly compared to correct sentences. This effect possibly indicates reduced integrative capacities of the ASD group. Furthermore, world knowledge anomalies elicited significantly stronger activation in right inferior frontal gyrus (RIFG) in the control group compared to the ASD group. This additional RIFG activation probably reflects revision of the situation model after new, conflicting information. The lack of recruitment of RIFG is possibly related to difficulties with exception handling in the ASD group.
10. Wintle RF, Lionel AC, Hu P, Ginsberg SD, Pinto D, Thiruvahindrapduram B, Wei J, Marshall CR, Pickett J, Cook EH, Scherer SW. {{A genotype resource for postmortem brain samples from the autism tissue program}}. {Autism Res};2011 (Jan 19)
The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype-phenotype correlation and interpretation of gene expression data derived from the banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community.
10. Worley JA, Matson JL, Mahan S, Kozlowski AM, Neal D. {{Stability of symptoms of autism spectrum disorders in toddlers: An examination using the Baby and Infant Screen for Children with aUtIsm Traits-Part 1 (BISCUIT)}}. {Dev Neurorehabil};2011;14(1):36-40.
Objective: The diagnostic stability of Autism Spectrum Disorders (ASD) at very young ages continues to be debated, despite empirical evidence that ASDs can be reliably diagnosed in children under the age of 3 years. This topic is of the upmost importance given that early intervention increases long-term outcomes in this population. Methods: The goal of the current study was to examine the stability of symptoms of ASD between two assessment times for 114 toddlers. The following was compared from the first to second assessment: diagnostic classification stability, correlations between scores and the impact of time between the first and second assessment. Results: Significant correlations were found for toddlers as young as 18 months of age. In addition, even with up to a year between assessment intervals, symptoms of ASD were relatively stable prior to 3 years of age. Conclusions: Implications of the current findings are discussed.
