1. Bremer A, Giacobini M, Eriksson M, Gustavsson P, Nordin V, Fernell E, Gillberg C, Nordgren A, Uppstromer A, Anderlid BM, Nordenskjold M, Schoumans J. {{Copy number variation characteristics in subpopulations of patients with autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2010 (Dec 8)
Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P = 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs. (c) 2010 Wiley-Liss, Inc.
2. Chevallier C, Noveck I, Happe F, Wilson D. {{What’s in a voice? Prosody as a test case for the Theory of Mind account of autism}}. {Neuropsychologia};2010 (Dec 3)
The human voice conveys a variety of information about people’s feelings, emotions and mental states. Some of this information relies on sophisticated Theory of Mind (ToM) skills, while others are more simple and do not require ToM. This variety provides an interesting test case for the ToM account of autism, which would predict greater impairment as ToM requirements increase. In this paper, we draw on psychological and pragmatic theories to classify vocal cues according to the amount of mindreading required to identify them. Children with a high functioning Autism Spectrum Disorder and matched controls were tested in three experiments where the speakers’ state had to be extracted from their vocalizations. Although our results confirm that people with autism have subtle difficulties dealing with vocal cues, they show a pattern of performance that is inconsistent with the view that atypical recognition of vocal cues is caused by impaired ToM.
3. Dichter GS, Felder JN, Green SR, Rittenberg AM, Sasson NJ, Bodfish JW. {{Reward circuitry function in autism spectrum disorders}}. {Soc Cogn Affect Neurosci};2010 (Dec 8)
Social interaction deficits and restricted repetitive behaviors and interests that characterize autism spectrum disorders (ASDs) may both reflect aberrant functioning of brain reward circuits. However, no neuroimaging study to date has investigated the integrity of reward circuits using an incentive delay paradigm in individuals with ASDs. In the present study, we used functional magnetic resonance imaging to assess blood-oxygen level-dependent activation during reward anticipation and outcomes in 15 participants with an ASD and 16 matched control participants. Brain activation was assessed during anticipation of and in response to monetary incentives and object image incentives previously shown to be visually salient for individuals with ASDs (e.g. trains, electronics). Participants with ASDs showed decreased nucleus accumbens activation during monetary anticipation and outcomes, but not during object anticipation or outcomes. Group x reward-type-interaction tests revealed robust interaction effects in bilateral nucleus accumbens during reward anticipation and in ventromedial prefrontal cortex during reward outcomes, indicating differential responses contingent on reward type in these regions. Results suggest that ASDs are characterized by reward-circuitry hypoactivation in response to monetary incentives but not in response to autism-relevant object images. The clinical implications of the double dissociation of reward type and temporal phase in reward circuitry function in ASD are discussed.
4. Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, Hansen R, Hertz-Picciotto I, Ashwood P, Van de Water J. {{Autoantibodies To Cerebellum In Children With Autism Associate With Behavior}}. {Brain Behav Immun};2010 (Dec 3)
Autism is a heterogeneous disorder with a poorly understood biological basis. Some children with autism harbor plasma autoantibodies that target brain proteins. Similarly, some mothers of children with autism produce antibodies specific to autism that target pairs of fetal brain proteins at 37/73 kDa and 39/73kDa. We explored the relationship between the presence of brain-specific autoantibodies and several behavioral characteristics of autism in 277 children with an autism spectrum disorder and 189 typically developing age-matched controls. Further, we used maternal autoantibody data to investigate potential familial relationships for the production of brain-directed autoantibodies. We demonstrated by western blot that autoantibodies specific for a 45kDa cerebellar protein in children were associated with a diagnosis of autism (p=0.017) while autoantibodies directed towards a 62kDa protein were associated with the broader diagnosis of autism spectrum disorder (ASD) (p=0.043). Children with such autoantibodies had lower adaptive (p=0.0008) and cognitive function (p=0.005), as well as increased aberrant behaviors (p<0.05) compared to children without these antibodies. No correlation was noted for those mothers with the most specific pattern of anti-fetal brain autoantibodies and children with the autoantibodies to either the 45 or 62 kDa bands. Collectively, these data suggest that antibodies towards brain proteins in children are associated with lower adaptive and cognitive function as well as core behaviors associated with autism. It is unclear whether these antibodies have direct pathologic significance, or if they are merely a response to previous injury. Future studies are needed to determine the identities of the protein targets and explore their significance in autism.
5. Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK. {{Rett syndrome: Revised diagnostic criteria and nomenclature}}. {Ann Neurol};2010 (Dec 8)
OBJECTIVE: Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. METHOD: RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. RESULTS: The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. INTERPRETATION: These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. Ann Neurol 2010.
6. Kistner-Griffin E, Brune CW, Davis LK, Sutcliffe JS, Cox NJ, Cook EH, Jr. {{Parent-of-origin effects of the serotonin transporter gene associated with autism}}. {Am J Med Genet B Neuropsychiatr Genet};2010 (Dec 8)
A promoter-linked insertion/deletion polymorphism of the serotonin transporter gene (SLC6A4) has been implicated in autism spectrum disorders (ASDs) in numerous family based association studies. However, the results of these investigations have been inconsistent in that both the long and short alleles have been shown to be over-transmitted to affected offspring. In order to further elucidate the relationship between the 5-HTTLPR variant and autism risk, we undertook a thorough study of parent-of-origin effects, maternal genotype effects, and offspring genotype effects in a sample of affected offspring from the Autism Genetic Resource Exchange (AGRE). Both the overall autism phenotype and measures of autism behaviors from the Autism Diagnostic Interview-Revised [Lord et al. (1994); J Autism Dev Disord 24(5): 659-685] were considered. We found evidence of over-transmission (risk allele short, P = 0.012), maternal effects (risk allele long, P = 0.035), and parent-of-origin effects (risk allele short from mother, P = 0.018) of the 5-HTTLPR variant in the AGRE sample. Population- and gender-specific effects were also explored as associations may be heterogeneous across populations and sexes. Parent-of-origin effects of the variant were associated with maternally inherited copies of the short allele that resulted in more impaired overall level of language (P = 0.04). Our study was conducted to further investigate the 5-HTTLPR risk variants by identifying allelic associations that may be population-specific, phenotype-specific, or conferred by maternal or parent-of-origin effects. In light of conflicting observations from previous studies, these are just a few of the possible explanations that deserve attention. (c) 2010 Wiley-Liss, Inc.
7. Rao S, Salmon G. {{Autism spectrum disorders}}. {Br J Hosp Med (Lond)};2010 (Dec);71(12):699-703.
The term autism spectrum disorder refers to a constellation of symptoms involving impairments in social interaction and communication, and restricted, repetitive behaviours and interests. This article highlights the disorder among professionals who may come into contact with people with autism spectrum disorder.
