1. Becker KG. {{Autism and urbanization}}. {Am J Public Health} (Jul);100(7):1156-1157; author reply 1157.
2. Bigham S, Boucher J, Mayes A, Anns S. {{Assessing recollection and familiarity in autistic spectrum disorders: methods and findings}}. {J Autism Dev Disord} (Jul);40(7):878-889.
We hypothesise that of the two processes underlying declarative memory, recollection is impaired in high-functioning autism (HFA) whereas recollection and familiarity are impaired in low-functioning autism (LFA). Testing these hypotheses necessitates assessing recollection and familiarity separately. However, this is difficult, because both processes contribute to performance on standard memory tests. Moreover, tests must be suitable for use with young or intellectually disabled participants. This study aimed to develop tests of recollection and familiarity separately, and to make preliminary tests of our hypotheses. We developed a temporal source memory task to assess recollection in LFA, and a shape recognition task to assess familiarity and an action recall task assessing recollection in HFA. The methods and implications of the results are discussed.
3. Chlebowski C, Green JA, Barton ML, Fein D. {{Using the childhood autism rating scale to diagnose autism spectrum disorders}}. {J Autism Dev Disord} (Jul);40(7):787-799.
This study investigated the childhood autism rating scale (CARS) as a tool for ASD diagnoses for 2-year-old (n = 376) and 4-year-old (n = 230) children referred for possible autism. The cut-off score to distinguish autistic disorder from PDD-NOS was 32 in the 2-year-old sample (consistent with Lord in J Child Psychol Psychiatry Allied Discipl, 36, 1365-1382, 1995), and 30 in the 4-year-old sample, with good sensitivity and specificity at both ages. The cut-off score to distinguish ASD from non-ASD at both ages was 25.5, with good sensitivity and specificity. Results confirm the utility of the CARS in distinguishing autistic disorder from PDD-NOS, and distinguishing ASD from other developmental disorders and typical development and suggest that an ASD cutoff around 25, which is in common clinical use, is valid.
4. Cukier HN, Rabionet R, Konidari I, Rayner-Evans MY, Baltos ML, Wright HH, Abramson RK, Martin ER, Cuccaro ML, Pericak-Vance MA, Gilbert JR. {{Novel variants identified in methyl-CpG-binding domain genes in autistic individuals}}. {Neurogenetics} (Jul);11(3):291-303.
Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these variations to disease etiology. Variants include a R23M alteration in two affected half brothers which falls within the MBD domain of the MBD3 protein, as well as a frameshift in MBD4 that is predicted to truncate almost half of the protein. These results suggest that rare cases of autism may be influenced by mutations in members of the dynamic MBD protein family.
5. Daisy S, Mohammad QD, Alam B, Hoque A, Haque B, Rahman KM, Khan SU. {{Epilepsy and abnormal electroencephalogram in children with autism spectrum disorder}}. {Mymensingh Med J} (Jul);19(2):264-266.
Epilepsy occurs in 30 to 40% of individuals with autism spectrum disorder (ASD). However the association of epilepsy or abnormal electroencephalogram is not known in our population. This study addresses the incidence of epilepsy and or abnormal electroencephalogram in Bangladeshi children with autism spectrum disorder. The clinical history and electroencephalogram of 18 children diagnosed with autism spectrum disorder were retrospectively reviewed. Forty four percent were diagnosed with epilepsy or abnormal electroencephalogram. This abnormal electroencephalogram or epilepsy occurred at significantly higher rates in children with more impaired range of autism spectrum disorder. These finding suggest that the use of neurological investigative technique such as electroencephalogram (EEG) should be considered routinely in children with autism spectrum disorder especially in more impaired individuals.
6. 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} (Jul);40(7):858-869.
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.
7. Esbensen AJ, Bishop SL, Seltzer MM, Greenberg JS, Taylor JL. {{Comparisons between Individuals with Autism Spectrum Disorders and Individuals with Down Syndrome in Adulthood}}. {Am J Intellect Dev Disabil} (Jul 1);115(4):277-290.
Differences between 70 adults with autism spectrum disorders (ASD) and intellectual disability and 70 age-matched adults with Down syndrome (DS) were examined on variables indicative of independence in adult life. Adults with ASD had less residential independence and social contact with friends, had more limited functional abilities and literacy, exhibited more behavior problems, had more unmet service needs, and received fewer services as compared to adults with DS. Reflecting these differences, adults with ASD were less likely to be classified as having high or moderate levels of independence in adult life as compared to adults with DS. Predictors of independence in adult life differed for adults with ASD as compared to adults with DS. Implications for service delivery are discussed.
8. Finnigan E, Starr E. {{Increasing social responsiveness in a child with autism: A comparison of music and non-music interventions}}. {Autism} (Jul);14(4):321-348.
This study sought to determine the effects of using music and non-music interventions on the social responsive and avoidant behaviours of a preschool child with autism. A single-subject alternating treatment design was used in which two interventions were presented in a similar fashion except for the addition of music during the music condition. Four phases took place: baseline (Phase A), alternating treatments (Phase B), a second treatment phase (Phase C) using the condition that proved to be more effective in Phase B, and follow-up (Phase D). Data were collected over a total of 12 treatment sessions for various social responsive and avoidant behaviours. Results indicated that the music intervention was more effective than the non-music intervention in increasing all three social responsive behaviours in both Phases B and C. Furthermore, no avoidant behaviours were observed during the music condition. It is suggested that the music condition was more motivating for the participant than the non-music condition, resulting in more social responsive behaviours.
9. Fletcher PT, Whitaker RT, Tao R, DuBray MB, Froehlich A, Ravichandran C, Alexander AL, Bigler ED, Lange N, Lainhart JE. {{Microstructural connectivity of the arcuate fasciculus in adolescents with high-functioning autism}}. {Neuroimage} (Jul 1);51(3):1117-1125.
The arcuate fasciculus is a white matter fiber bundle of great importance in language. In this study, diffusion tensor imaging (DTI) was used to infer white matter integrity in the arcuate fasciculi of a group of subjects with high-functioning autism and a control group matched for age, handedness, IQ, and head size. The arcuate fasciculus for each subject was automatically extracted from the imaging data using a new volumetric DTI segmentation algorithm. The results showed a significant increase in mean diffusivity (MD) in the autism group, due mostly to an increase in the radial diffusivity (RD). A test of the lateralization of DTI measurements showed that both MD and fractional anisotropy (FA) were less lateralized in the autism group. These results suggest that white matter microstructure in the arcuate fasciculus is affected in autism and that the language specialization apparent in the left arcuate of healthy subjects is not as evident in autism, which may be related to poorer language functioning.
10. Frankel F, Myatt R, Sugar C, Whitham C, Gorospe CM, Laugeson E. {{A randomized controlled study of parent-assisted Children’s Friendship Training with children having autism spectrum disorders}}. {J Autism Dev Disord} (Jul);40(7):827-842.
This study evaluated Children’s Friendship Training (CFT), a manualized parent-assisted intervention to improve social skills among second to fifth grade children with autism spectrum disorders. Comparison was made with a delayed treatment control group (DTC). Targeted skills included conversational skills, peer entry skills, developing friendship networks, good sportsmanship, good host behavior during play dates, and handling teasing. At post-testing, the CFT group was superior to the DTC group on parent measures of social skill and play date behavior, and child measures of popularity and loneliness, At 3-month follow-up, parent measures showed significant improvement from baseline. Post-hoc analysis indicated more than 87% of children receiving CFT showed reliable change on at least one measure at post-test and 66.7% after 3 months follow-up.
11. Georgiades S, Papageorgiou V, Anagnostou E. {{Brief report: Repetitive behaviours in Greek individuals with autism spectrum disorder}}. {J Autism Dev Disord} (Jul);40(7):903-906.
The main objective of this study was to examine the factor structure of restricted repetitive behaviours (RRBs) in a sample of 205 Greek individuals with Autism Spectrum Disorder (ASD), using the Repetitive Behavior Scale-Revised (RBS-R). Results show that the structure of RRBs in this Greek sample can be described using a 2-factor solution. The current study provides further, cross-cultural support for the distinction between a « high-order » factor reflecting compulsions, rituals, sameness, and restricted behaviours (CRSRB) and a « low-order » factor reflecting stereotyped movements and self-injurious behaviours (SSIB). These factors are most likely located at the top of the RRB structural hierarchy and represent general, independent constructs of ASD behaviours that can be identified not only across studies but also across cultures.
12. Gold R, Faust M. {{Right hemisphere dysfunction and metaphor comprehension in young adults with Asperger syndrome}}. {J Autism Dev Disord} (Jul);40(7):800-811.
This study examined whether the known difficulties in metaphor comprehension exhibited by persons with Asperger syndrome (AS) can be explained by a dysfunctional right hemisphere (RH). Using the divided visual field paradigm, 27 AS participants and 36 matched controls were presented with word pairs of four types (literal, conventional metaphors, novel metaphors, and unrelated word pairs), and were asked to perform a semantic judgment task. The main hypothesis was that whereas the control group participants will show RH superiority for novel metaphor processing, no RH superiority will be found in the AS group. Results indeed indicate much less RH contribution to novel metaphor comprehension in AS, and are discussed in light of linguistic models and the neurobiology of autism.
13. Iarocci G, Rombough A, Yager J, Weeks DJ, Chua R. {{Visual influences on speech perception in children with autism}}. {Autism} (Jul);14(4):305-320.
The bimodal perception of speech sounds was examined in children with autism as compared to mental age-matched typically developing (TD) children. A computer task was employed wherein only the mouth region of the face was displayed and children reported what they heard or saw when presented with consonant-vowel sounds in unimodal auditory condition, unimodal visual condition, and a bimodal condition. Children with autism showed less visual influence and more auditory influence on their bimodal speech perception as compared to their TD peers, largely due to significantly worse performance in the unimodal visual condition (lip reading). Children with autism may not benefit to the same extent as TD children from visual cues such as lip reading that typically support the processing of speech sounds. The disadvantage in lip reading may be detrimental when auditory input is degraded, for example in school settings, whereby speakers are communicating in frequently noisy environments.
14. Kim SH, Lord C. {{Restricted and repetitive behaviors in toddlers and preschoolers with autism spectrum disorders based on the Autism Diagnostic Observation Schedule (ADOS)}}. {Autism Res} (Jun 29)
Restricted and repetitive behaviors (RRBs) observed during the Autism Diagnostic Observation Schedule [ADOS: Lord et al., 2000] were examined in a longitudinal data set of 455 toddlers and preschoolers (age 8-56 months) with clinical diagnosis of Autism Spectrum Disorders (ASD; autism, n=121 and pervasive developmental disorders-not otherwise specified (PDD-NOS), n=71), a nonspectrum disorder (NS; n=90), or typical development (TD; n=173). Even in the relatively brief semi-structured observations, GEE analyses of the severity and prevalence of RRBs differentiated children with ASD from those with NS and TD across all ages. RRB total scores on the ADOS were stable over time for children with ASD and NS; however, typically developing preschoolers showed lower RRB scores than typically developing toddlers. Nonverbal IQ (NVIQ) was more strongly related to the prevalence of RRBs in older children with PDD-NOS, NS, and TD than younger children under 2 years and those with autism. Item analyses revealed different relationships between individual items and NVIQ, age, diagnosis, and gender. These findings are discussed in terms of their implications for the etiology and treatment of RRBs as well as for the framework of ASD diagnostic criteria in future diagnostic systems.
15. Kokina A, Kern L. {{Social Story interventions for students with autism spectrum disorders: a meta-analysis}}. {J Autism Dev Disord} (Jul);40(7):812-826.
A meta-analysis of single-subject research was conducted, examining the use of Social Stories and the role of a comprehensive set of moderator variables (intervention and participant characteristics) on intervention outcomes. While Social Stories had low to questionable overall effectiveness, they were more effective when addressing inappropriate behaviors than when teaching social skills. Social Stories also seemed to be associated with improved outcomes when used in general education settings and with target children as their own intervention agents. The role of other variables of interest, such as participants’ age, diagnosis, and skill development, the format of Social Stories, the length of the intervention, and the use of assessment (e.g., comprehension checks) also was explored.
16. Lam SF, Wong BP, Leung D, Ho D, Au-Yeung P. {{How Parents Perceive and Feel about Participation in Community Activities: The Comparison between Parents of Preschoolers with and without Autism Spectrum Disorders}}. {Autism} (Jul);14(4):359-377.
The present study compared how parents of preschoolers with and without Autism Spectrum Disorders (ASD) perceived and felt about participation in community activities. A questionnaire survey was conducted with 380 Hong Kong parents of preschoolers with ASD and 214 Hong Kong parents of preschoolers without ASD. The two groups were not different in their willingness and frequency of participation in community activities. However, the psychological processes underneath their willingness were very different. Among the parents of preschoolers with ASD, their willingness was associated with how they perceived the difficulty and importance of the participation and what emotions they experienced during the activities. This pattern of association was not evident among the parents of preschoolers without ASD.
17. Laumonnier F, Shoubridge C, Antar C, Nguyen LS, Van Esch H, Kleefstra T, Briault S, Fryns JP, Hamel B, Chelly J, Ropers HH, Ronce N, Blesson S, Moraine C, Gecz J, Raynaud M. {{Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism}}. {Mol Psychiatry} (Jul);15(7):767-776.
Mutations in the UPF3B gene, which encodes a protein involved in nonsense-mediated mRNA decay, have recently been described in four families with specific (Lujan-Fryns and FG syndromes), nonspecific X-linked mental retardation (XLMR) and autism. To further elucidate the contribution of UPF3B to mental retardation (MR), we screened its coding sequence in 397 families collected by the EuroMRX consortium. We identified one nonsense mutation, c.1081C>T/p.Arg361(*), in a family with nonspecific MR (MRX62) and two amino-acid substitutions in two other, unrelated families with MR and/or autism (c.1136G>A/p.Arg379His and c.1103G>A/p.Arg368Gln). Functional studies using lymphoblastoid cell lines from affected patients revealed that c.1081C>T mutation resulted in UPF3B mRNA degradation and consequent absence of the UPF3B protein. We also studied the subcellular localization of the wild-type and mutated UPF3B proteins in mouse primary hippocampal neurons. We did not detect any obvious difference in the localization between the wild-type UPF3B and the proteins carrying the two missense changes identified. However, we show that UPF3B is widely expressed in neurons and also presents in dendritic spines, which are essential structures for proper neurotransmission and thus learning and memory processes. Our results demonstrate that in addition to Lujan-Fryns and FG syndromes, UPF3B protein truncation mutations can cause also nonspecific XLMR. We also identify comorbidity of MR and autism in another family with UPF3B mutation. The neuronal localization pattern of the UPF3B protein and its function in mRNA surveillance suggests a potential function in the regulation of the expression and degradation of various mRNAs present at the synapse.
18. Liao P, Soong TW. {{CaV1.2 channelopathies: from arrhythmias to autism, bipolar disorder, and immunodeficiency}}. {Pflugers Arch} (Jul);460(2):353-359.
Mutations of human CaV1.2 channel gene were identified only recently. The gain-of-function mutations were found at two mutually exclusive exons in patients with Timothy syndrome (TS). These patients exhibit prolonged QT interval and lethal cardiac arrhythmias. In contrast, the loss-of-function mutations of CaV1.2 channel in patients with Brugada syndrome produce short QT interval that could result in sudden cardiac death. TS patients also suffer from multi-organ dysfunction that includes neurological disorder such as autism and mental retardation reflecting the wide tissue distribution of CaV1.2 channel. Mutations found on different mutually exclusive exons determine the severity of the disease. Unexpectedly, TS patients may develop recurrent infections and bronchitis that suggests a role of CaV1.2 channel in the immune system. Furthermore, recent reports revealed a linkage of CaV1.2 channel polymorphism with multiple central nervous system disorders including bipolar disorder, depression, and schizophrenia. Here, we will discuss how alternative splicing modulates CaV1.2 channelopathy and the role of CaV1.2 channel in both excitable and non-excitable tissues.
19. Loirat C, Bellanne-Chantelot C, Husson I, Deschenes G, Guigonis V, Chabane N. {{Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion}}. {Nephrol Dial Transplant} (Jun 28)
BACKGROUND: We report autism in 3 out of 53 children with cystic or hyperechogenic kidneys and heterozygous 17q12 region deletion encompassing hepatocyte nuclear factor-1beta (HNF1B). RESULTS: They presented mental retardation, social interaction impairments, verbal and non-verbal communication deficits and stereotyped behaviours. Deletion size and location of breakpoints were similar to those reported in patients with renal disease/diabetes only. CONCLUSION: Reciprocal genomic rearrangements of the 17q12 region, reported in patients with mental retardation and epilepsy, could also be involved in autism. Nephrologists should be aware of the possibility of autism in patients with 17q12 deletion including HNF1B locus.
20. McGonigle-Chalmers M, Alderson-Day B. {{Free classification as a window on executive functioning in autism spectrum disorders}}. {J Autism Dev Disord} (Jul);40(7):844-857.
Spontaneous classification was assessed using a free serial search task in 18 school-aged children at the high functioning end of the autistic spectrum and compared with results from age-matched typically developing controls. The task required participants to touch shapes in an exhaustive non-repetitive sequence. The positions of the items varied randomly between touches. The objective was to measure the extent to which children with autism and Asperger’s syndrome could spontaneously utilise category information such as shape and color to organise their search. There were no group differences on measures of sequential control and levels of categorization once age and IQ had been partialled out. The results are contrasted with findings from the same lab using a size seriation task.
21. Morsanyi K, Holyoak KJ. {{Analogical reasoning ability in autistic and typically developing children}}. {Dev Sci} (Jul);13(4):578-587.
Abstract Recent studies (e.g. Dawson et al., 2007) have reported that autistic people perform in the normal range on the Raven Progressive Matrices test, a formal reasoning test that requires integration of relations as well as the ability to infer rules and form high-level abstractions. Here we compared autistic and typically developing children, matched on age, IQ, and verbal and non-verbal working memory, using both the Raven test and pictorial tests of analogical reasoning. Whereas the Raven test requires only formal analogical reasoning, the other analogy tests require use of real-world knowledge, as well as inhibition of salient distractors. We found that autistic children performed as well as controls on all these tests of reasoning with relations. Our findings indicate that the basic ability to reason systematically with relations, for both abstract and thematic materials, is intact in autism.
22. Norris M, Lecavalier L. {{Screening accuracy of level 2 autism spectrum disorder rating scales: a review of selected instruments}}. {Autism} (Jul);14(4):263-284.
The goal of this review was to examine the state of Level 2, caregiver-completed rating scales for the screening of Autism Spectrum Disorders (ASDs) in individuals above the age of three years. We focused on screening accuracy and paid particular attention to comparison groups. Inclusion criteria required that scales be developed post ICD-10, be ASD-specific, and have published evidence of diagnostic validity in peer-reviewed journals. The five scales reviewed were: the Social Communication Questionnaire (SCQ), Gilliam Autism Rating Scale/Gilliam Autism Rating Scale-Second Edition (GARS/GARS-2), Social Responsiveness Scale (SRS), Autism Spectrum Screening Questionnaire (ASSQ), and Asperger Syndrome Diagnostic Scale (ASDS). Twenty total studies were located, most examining the SCQ. Research on the other scales was limited. Comparisons between scales were few and available evidence of diagnostic validity is scarce for certain subpopulations (e.g., lower functioning individuals, PDDNOS). Overall, the SCQ performed well, the SRS and ASSQ showed promise, and the GARS/GARS-2 and ASDS demonstrated poor sensitivity. This review indicates that Level 2 ASD caregiver-completed rating scales are in need of much more scientific scrutiny.
23. Odent M. {{Autism and anorexia nervosa: Two facets of the same disease?}}. {Med Hypotheses} (Jul);75(1):79-81.
We compiled data included in the Primal Health Research Database (www.primalhealthresearch.com) to test the hypothesis that when two pathological conditions or personality traits share the same critical period for gene-environment interaction, we should expect further similarities, particularly from clinical and pathophysiological perspectives. The keywords ‘autism’ and ‘anorexia nervosa’ (but not bulimia nervosa) lead to studies suggesting that for both conditions the perinatal period is critical. We take this example to look at other possible links between these pathological entities. From a clinical perspective, several teams have independently emphasized the importance of autistic traits in anorexia nervosa. Deficits in the processing of oxytocin have been demonstrated in both cases. Autistic groups have significantly lower blood oxytocin levels than normal groups, and oxytocin levels increase with age in the normal group only. In autistic groups there is a high ratio of intermediates of oxytocin synthesis (OX-T) to the nonapeptide oxytocin (OT). On the other hand, it has been reported that the level of oxytocin in the cerebrospinal fluid of anorexic women is significantly lower than the level of oxytocin in bulimic and control subjects. Scanning data reveal similar asymmetric functions with left hemisphere preponderance in autistic spectrum disorders and anorexia. A comparative study of the mirror neurons systems is another promising avenue for research. Such an accumulation of similarities from a great diversity of perspectives suggests that anorexia nervosa might be considered a female variant of the autistic spectrum. A plausible interpretation is that prenatal exposure to male hormones might protect against the expression of this disease: girls who have a twin brother are at low risk for anorexia nervosa, compared with girls who have a twin sister, and with controls; furthermore genetic linkage analyses do not detect change on the X chromosome. From an overview of the database, the perinatal period appears to be critical for all disorders related to the capacity to love (including love of oneself), to the potential for aggression (including self-destructive behaviours), or to sociability. Is the perinatal period critical for the organisation of the oxytocin system? This is an important question at a time when we learn that the widely used synthetic oxytocin can probably diffuse across the placenta. On the other hand, where the genesis of metabolic types is concerned, it is prenatal life that appears to be critical.
24. Randi J, Newman T, Grigorenko EL. {{Teaching children with autism to read for meaning: challenges and possibilities}}. {J Autism Dev Disord} (Jul);40(7):890-902.
The purpose of this literature review is to examine what makes reading for understanding especially challenging for children on the autism spectrum, most of whom are skilled at decoding and less skilled at comprehension. This paper first summarizes the research on reading comprehension with a focus on the cognitive skills and processes that are involved in gaining meaning from text and then reviews studies of reading comprehension deficits in children on the spectrum. The paper concludes with a review of reading comprehension interventions for children on the spectrum. These children can especially benefit from interventions addressing particular cognitive processes, such as locating antecedent events, generating and answering questions, locating referents, and rereading to repair understanding.
25. Sadakata T, Furuichi T. {{Ca(2+)-dependent activator protein for secretion 2 and autistic-like phenotypes}}. {Neurosci Res} (Jul);67(3):197-202.
Ca(2+)-dependent activator protein for secretion 2 (CAPS2 or CADPS2) regulates dense-core vesicle (DCV) exocytosis. We found that CAPS2 is involved in the secretion of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and that CAPS2 KO mice not only have deficits in neuronal development and survival but also exhibit abnormal behaviors, including impaired social interaction, hyperactivity, an abnormal sleep-wake rhythm and increased anxiety in unfamiliar environments. Moreover, we identified increased expression of a rare CAPS2 splice variant in autism patients that specifically lacks exon 3 and that is not transported to axons when exogenously expressed in mouse cortical neurons. Moreover, non-synonymous SNPs have been identified in some autistic patients. These results implicate CAPS2 in autism susceptibility. Therefore, CAPS2 KO mice will be a useful animal model to study the aspects of the neuropathology and behavior characteristics of neurodevelopmental disorders.
26. Silverman JL, Yang M, Lord C, Crawley JN. {{Behavioural phenotyping assays for mouse models of autism}}. {Nat Rev Neurosci} (Jul);11(7):490-502.
Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100-150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of austism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.
27. Stoltenberg C, Schjolberg S, Bresnahan M, Hornig M, Hirtz D, Dahl C, Lie KK, Reichborn-Kjennerud T, Schreuder P, Alsaker E, Oyen AS, Magnus P, Suren P, Susser E, Lipkin WI. {{The Autism Birth Cohort: a paradigm for gene-environment-timing research}}. {Mol Psychiatry} (Jul);15(7):676-680.
The reported prevalence of autism spectrum disorders (ASDs) has increased by 5- to 10-fold over the past 20 years. Whether ASDs are truly more frequent is controversial; nonetheless, the burden is profound in human and economic terms. Although autism is among the most heritable of mental disorders, its pathogenesis remains obscure. Environmental factors are proposed; however, none is implicated. Furthermore, there are no biomarkers to screen for ASD or risk of ASD. The Autism Birth Cohort (ABC) was initiated to analyze gene x environment x timing interactions and enable early diagnosis. It uses a large, unselected birth cohort in which cases are prospectively ascertained through population screening. Samples collected serially through pregnancy and childhood include parental blood, maternal urine, cord blood, milk teeth and rectal swabs. More than 107,000 children are continuously screened through questionnaires, referral, and a national registry. Cases are compared with a control group from the same cohort in a ‘nested case-control’ design. Early screening and diagnostic assessments and re-assessments are designed to provide a rich view of longitudinal trajectory. Genetic, proteomic, immunologic, metagenomic and microbiological tools will be used to exploit unique biological samples. The ABC is a paradigm for analyzing the role of genetic and environmental factors in complex disorders.
28. Sutherland A, Crewther DP. {{Magnocellular visual evoked potential delay with high autism spectrum quotient yields a neural mechanism for altered perception}}. {Brain} (Jul);133(Pt 7):2089-2097.
Everyone has autistic characteristics to a greater or lesser degree, encapsulated in the Autism Spectrum Quotient, a scale that measures the degree to which an adult of normal intelligence displays traits associated with autism spectrum disorders. Recent psychophysical analyses of autism spectrum disorders point to superior local processing, and impaired or ignored global and contextual processing. The aim of this study was to test whether low- and high-scoring individuals on the Autism Spectrum Quotient differ on a measure of local and global processing, motion processing and visual pathway integrity. Fifteen low-scoring individuals and 14 high-scoring individuals derived from a normal population participated in the study. The results indicate that the initial cortical response to the magnocellular afferents is weaker at low contrast in the high autistic tendency group and that a second-order response, reflecting magnocellular activity, demonstrated a delay for high versus low scorers when the parvocellular pathway was also active in response to a high contrast stimulus. High-scoring individuals also demonstrated difficulty in identifying the global components of locally salient hierarchical Navon figures. Furthermore, cross-validated discriminant analysis, using four physiologically and three psychophysically derived parameters, correctly classified 83% of individuals who scored either high or low on the Autism Spectrum Quotient. These findings in the group scoring high on the Autism Spectrum Quotient indicate that a delay in primary visual/prestriate cortical processing of magnocellular input diminishes the advantage of its early arrival to primary visual cortex. This appears to be associated with impaired global visual perception, predicting with high accuracy behavioural tendencies associated with autism spectrum disorders. It has been proposed that perceptual impairment in autism may be attributed to a dysfunction of horizontal connections within early visual areas, presumably parvocellular in nature. However, the timing of such form processing aberrations is much later than the timing of abnormal magnocellular visual processing measured directly here. Thus it is proposed that a magnocellular processing delay decreases the ability of autistic individuals to benefit perceptually from feedback normally associated with the magnocellular advantage.
29. Toal F, Daly EM, Page L, Deeley Q, Hallahan B, Bloemen O, Cutter WJ, Brammer MJ, Curran S, Robertson D, Murphy C, Murphy KC, Murphy DG. {{Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study}}. {Psychol Med} (Jul);40(7):1171-1181.
BACKGROUND: Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype. METHOD: We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender. RESULTS: VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome. CONCLUSIONS: Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.
30. Wachtel LE, Dhossche DM. {{Self-injury in autism as an alternate sign of catatonia: implications for electroconvulsive therapy}}. {Med Hypotheses} (Jul);75(1):111-114.
Multiple reports show the efficacious usage of ECT for catatonia in individuals with autism. There are also a few reports showing that ECT improves self-injury in people with and without autism. In this hypothesis, self-injury in autism and other developmental disorders may be an alternate sign of catatonia, and as such an indication for electroconvulsive therapy. The issue is important because self-injury occurs at an increased rate in autistic and intellectually disabled individuals, but is poorly understood and often difficult to treat with psychological and pharmacological means. Self-injury may be considered a type of stereotypy, a classic symptom of catatonia that is exquisitely responsive to electroconvulsive therapy (ECT). Historical and modern reports further support the association of self-injury, tics and catatonia. Central gamma-aminobutyric acid (GABA) dysfunction may provide an important explanatory link between autism, catatonia and self-injury. Therefore, people with autism and other developmental disorders who develop severe self-injury (with or without concomitant tics) should be assessed for catatonia, and ECT should be considered as a treatment option. Further studies of the utility of ECT as an accepted treatment for catatonia are warranted in the study of self-injury in autism.
31. Wachtel LE, Griffin MM, Dhossche DM, Reti IM. {{Brief report: Electroconvulsive therapy for malignant catatonia in an autistic adolescent}}. {Autism} (Jul);14(4):349-358.
A 14-year-old male with autism and mild mental retardation developed malignant catatonia characterized by classic symptoms of catatonia, bradycardia and hypothermia. Bilateral electroconvulsive therapy and lorazepam were required for resolution. The case expands the occurrence of catatonia in autism into its malignant variant.
32. Wang L, Angley MT, Sorich MJ, Young RL, McKinnon RA, Gerber JP. {{Is there a role for routinely screening children with autism spectrum disorder for creatine deficiency syndrome?}}. {Autism Res} (Jun 29)
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that presents in the first three years of life. Currently, diagnosis of ASD is based on its behavioural manifestations, as laboratory diagnostic tests do not exist. Creatine deficiency syndrome (CDS) is one form of inborn error of metabolism where affected individuals have similar clinical features to individuals with ASD. Abnormal urinary creatine (CR) and guanidinoacetate (GAA) levels have been reported as biomarkers of CDS. We hypothesized that screening for abnormal levels of urinary CR and GAA in children with ASD may assist in identifying a subgroup of ASD individuals who can be managed with dietary interventions. Morning urine samples were collected from children with and without autism and analyzed for CR and GAA levels. Results showed there was no statistically significant difference in urinary CR:creatinine and GAA:creatinine between the children with ASD and sibling or unrelated controls. In conclusion, routine screening for abnormal urinary CR and GAA could be considered in ASD diagnostic protocols; however, individuals positive for CDS are likely to be rare in an ASD cohort.
33. Williams D, Happe F. {{Recognising ‘social’ and ‘non-social’ emotions in self and others: A study of autism}}. {Autism} (Jul);14(4):285-304.
Studies of emotion processing in autism have produced mixed results, with fewer studies observing autism-specific deficits than might be imagined. In the current study, 21 individuals with autism and 21 age- and ability-matched, learning disabled comparison participants were tested for their ability to (a) recognise, in others, expressions of ‘social’ emotions (e.g., embarrassment) and ‘non-social’ emotions (e.g., happiness) and; (b) report their own previous experiences of each of these emotions. In line with predictions, amongst both groups of participants, social emotions were more difficult to recognise and report than non-social emotions. Also amongst both groups, the ability to report social emotion-experience was significantly associated with the ability to recognise social emotions in others, independent of age and verbal ability. However, contrary to predictions, no between-group differences in levels or patterns of performance on the experimental tasks were observed. In light of previous research, these results suggest either that emotion-processing is not as specifically impaired in autism as is traditionally thought to be the case, or that individuals with autism are implementing compensatory strategies to succeed on experimental tasks in the absence of emotion-processing competence.
34. Williams DM, Jarrold C. {{Brief report: Predicting inner speech use amongst children with autism spectrum disorder (ASD): the roles of verbal ability and cognitive profile}}. {J Autism Dev Disord} (Jul);40(7):907-913.
Studies of inner speech use in ASD have produced conflicting results. Lidstone et al., J Autism Dev Disord (2009) hypothesised that Cognitive Profile (i.e., discrepancy between non-verbal and verbal abilities) is a predictor of inner speech use amongst children with ASD. They suggested other, contradictory results might be explained in terms of the different composition of ASD samples (in terms of Cognitive Profile) in each study. To test this, we conducted a new analysis of Williams et al.’s, J Child Psychol Psychiatry 48(1): 51-58 (2008) data on inner speech use in ASD. This revealed verbal ability predicted inner speech use on a short-term memory task over and above Cognitive Profile, but not vice versa. This suggests multiple factors determine whether children with ASD employ verbal mediation.
35. Williams EL, Casanova MF. {{Potential teratogenic effects of ultrasound on corticogenesis: implications for autism}}. {Med Hypotheses} (Jul);75(1):53-58.
The phenotypic expression of autism, according to the Triple Hit Hypothesis, is determined by three factors: a developmental time window of vulnerability, genetic susceptibility, and environmental stressors. In utero exposure to thalidomide, valproic acid, and maternal infections are examples of some of the teratogenic agents which increase the risk of developing autism and define a time window of vulnerability. An additional stressor to genetically susceptible individuals during this time window of vulnerability may be prenatal ultrasound. Ultrasound enhances the genesis and differentiation of progenitor cells by activating the nitric oxide (NO) pathway and related neurotrophins. The effects of this pathway activation, however, are determined by the stage of development of the target cells, local concentrations of NO, and the position of nuclei (basal versus apical), causing consequent proliferation at some stages while driving differentiation and migration at others. Ill-timed activation or overactivation of this pathway by ultrasound may extend proliferation, increasing total cell number, and/or may trigger precipitous migration, causing maldistribution of neurons amongst cortical lamina, ganglia, white matter, and germinal zones. The rising rates of autism coincident with the increased use of ultrasound in obstetrics and its teratogenic/toxic effects on the CNS demand further research regarding a putative correlation.
