1. Bremer A, Giacobini M, Nordenskjold M, Brondum-Nielsen K, Mansouri M, Dahl N, et al. {{Screening for copy number alterations in loci associated with autism spectrum disorders by two-color multiplex ligation-dependent probe amplification}}. {Am J Med Genet B Neuropsychiatr Genet}. Jan 5;153B(1):280-5.
The autism spectrum disorder (ASD) is a heterogenous condition characterized by impaired socialization and communication in association with stereotypic behaviors. ASD is highly heritable and heterogeneous with a complex genetic etiology. Recurrent submicroscopic deletions or duplications have been identified in a subgroup of individuals with ASD using array technology. Adequate genetic testing for these genomic imbalances have not yet been widely implemented in the diagnostic setting due to lack of feasible and cost-effective methods as well as difficulties to interpret the clinical significance of these small copy number variants (CNVs). We developed a multiplex ligation-dependent probe amplification (MLPA) assay to investigate its usefulness for detection of copy number alterations (CNAs) in autistic patients. This test proved to be easy to perform, fast, cost-effective, and suitable for reliable detection of multiple loci in a single reaction. We screened 148 autistic patients for 15 different loci covering 26 genes and found a 15q11-13 interstitial duplication that had escaped detection by conventional karyotyping in 1.3% of the patients. Synthetic probe MLPA allows for a flexible analysis of a continuously increasing number of CNAs associated with autism. Our result show that MLPA assay is an easy and cost-effective method for the identification of selected CNAs in diagnostic laboratories.
2. Dichter GS, Benning SD, Holtzclaw TN, Bodfish JW. {{Affective Modulation of the Startle Eyeblink and Postauricular Reflexes in Autism Spectrum Disorder}}. {J Autism Dev Disord}. Jan 5.
Eyeblink and postauricular reflexes to standardized affective images were examined in individuals without (n = 37) and with (n = 20) autism spectrum disorders (ASDs). Affective reflex modulation in control participants replicated previous findings. The ASD group, however, showed anomalous reflex modulation patterns, despite similar self-report ratings of pictures. Specifically, the ASD group demonstrated exaggerated eyeblink responses to pleasant images and exaggerated postauricular responses to unpleasant images. Although ASD is often conceptualized in terms of specific deficits in affective responding in the social domain, the present results suggest a domain-general pattern of deficits in affective processing and that such deficits may arise at an early phase in the stream of information processing.
3. Drake JE, Redash A, Coleman K, Haimson J, Winner E. {{‘Autistic’ Local Processing Bias also Found in Children Gifted in Realistic Drawing}}. {J Autism Dev Disord}. Jan 5.
We investigated whether typically-developing children with a gift for drawing realistically show the local processing bias seen in individuals with autism spectrum disorder (ASD). Twenty-seven 6-12 year-olds made an observational drawing (scored for level of realism) and completed three local processing tasks, and parents completed the Childhood Asperger Syndrome Test (CAST). Drawing score predicted local processing performance on all tasks independently of verbal IQ, age, and years of art lessons. Drawing score also predicted more frequent repetitive behaviors as assessed by the CAST. Thus, skill in realistic drawing is associated with a strong local processing bias and a tendency towards repetitive behaviors, showing that traits found in individuals with ASD irrespective of artistic talent are also found in typically developing children with artistic talent.
4. Hoekstra RA, Wheelwright S. {{Autistic traits in simplex and multiplex autism families: Focus on unaffected relatives}}. {Am J Med Genet B Neuropsychiatr Genet}. Jan 5;153B(1):356-8.
5. Klein JL, Macdonald RF, Vaillancourt G, Ahearn WH, Dube WV. {{Teaching Discrimination of Adult Gaze Direction to Children with Autism}}. {Res Autism Spectr Disord}. 2009 Jan 1;3(1):42-9.
Three young children diagnosed with autism did not reliably locate objects in the environment on the basis of an adult’s gaze shifts. A training program designed to teach gaze following used the activation of remote controlled mechanical toys as both prompts and consequences. Over several training sessions, toy activation was progressively delayed following the adult’s gaze-shift cues. All of the children eventually came to anticipate the toy activation and locate the target object on the basis of the adult’s gaze-shift cue alone. Discrimination of another person’s gaze direction is discussed in relation to joint attention deficits in children with autism.
6. Schaevitz LR, Moriuchi JM, Nag N, Mellot TJ, Berger-Sweeney J. {{Cognitive and social function and growth factors in a mouse model of Rett syndrome}}. {Physiol Behav}. 2009 Dec 30.
Rett syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormalities in social behavior, stereotyped movements, and restricted interests are common features in both RTT and classic autism. While mouse models of both RTT and autism exist, social behaviors have not been explored extensively in mouse models of RTT. Here, we report cognitive and social abnormalities in Mecp2(1lox) null mice, an animal model of RTT. The null mice show severe deficits in short- and long-term object recognition memory, reminiscent of the severe cognitive deficits seen in RTT girls. Social behavior, however, is abnormal in that the null mice spend more time in contact with stranger mice than do wildtype controls. These findings are consistent with reports of increased reciprocal social interaction in RTT girls relative to classic autism. We also report here that levels of the neurotrophins brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and nerve growth factor (NGF) are decreased in the hippocampus of the null mice, and discuss how this may provide an underlying mechanism for both the cognitive deficits and the increased motivation for social contact observed in the Mecp2(1lox) null mice. These studies support a differential etiology between RTT and autism, particularly with respect to sociability deficits.
7. Schreibman L, Stahmer AC, Barlett VC, Dufek S. {{Brief Report: Toward Refinement of a Predictive Behavioral Profile for Treatment Outcome in Children with Autism}}. {Res Autism Spectr Disord}. 2009 Jan;3(1):163-72.
Previously researchers identified a behavioral profile that predicted treatment response of children with autism to a specific behavioral intervention, Pivotal Response Training (PRT). This preliminary investigation sought to refine this profile by obtaining six participants matching the original nonresponder profile on all but one of the profile behaviors (toy contact or avoidance) and then assessing their response to PRT. In addition, participants received a course of Discrete Trial Training (DTT) to determine whether the profile predicted child response to this intervention. Altering the original profile behavior of toy contact led to improved response to PRT while, altering the profile behavior of high avoidance had little impact on treatment response, and the profile was not predictive of response to DTT.
