1. Adamson LB, Deckner DF, Bakeman R. {{Early interests and joint engagement in typical development, autism, and Down syndrome}}. {J Autism Dev Disord} (Jun);40(6):665-676.
This study examines how spontaneous interests in people and in objects relate to joint engagement in typically developing toddlers and young children with autism or Down syndrome. Ratings of interests were made repeatedly during intermissions in a laboratory-based protocol focused on caregiver-child interactions. Interests were moderated by diagnosis and relatively stable across intermissions. In autism, interest in people tended to be low and to decline rapidly, and the balance of interests favored familiar objects over people. Lower interest in people and in unfamiliar objects was associated with less coordinated joint engagement and with less steep developmental trajectories for symbol-infused joint engagement. These findings suggest that variations in interests may contribute to differences in the child’s engagement during social interactions that facilitate the acquisition of language.
2. Bauminger N, Solomon M, Rogers SJ. {{Predicting friendship quality in autism spectrum disorders and typical development}}. {J Autism Dev Disord} (Jun);40(6):751-761.
The role played by social relationship variables (attachment security; mother-child relationship qualities) and social-cognitive capacities (theory of mind) was examined in both observed friendship behaviors and in children’s descriptions of friendships (age 8-12) with high functioning children with autism spectrum disorders (HFASD) (n = 44) and with typical development (TYP) (n = 38). Overall, half of the HFASD sample (54.45%) reported maternal attachment security, corroborating data from younger children with ASD. The hypothesized predictors and their interrelations had both direct and indirect effects on friendship for both groups of children, highlighting the importance of these factors in children’s friendship development and suggesting both compensatory and amplification mechanisms for friendship qualities. Practical and clinical implications are discussed for friendship support in both ASD and TYP.
3. Berkel S, Marshall CR, Weiss B, Howe J, Roeth R, Moog U, Endris V, Roberts W, Szatmari P, Pinto D, Bonin M, Riess A, Engels H, Sprengel R, Scherer SW, Rappold GA. {{Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation}}. {Nat Genet} (Jun);42(6):489-491.
Using microarrays, we identified de novo copy number variations in the SHANK2 synaptic scaffolding gene in two unrelated individuals with autism-spectrum disorder (ASD) and mental retardation. DNA sequencing of SHANK2 in 396 individuals with ASD, 184 individuals with mental retardation and 659 unaffected individuals (controls) revealed additional variants that were specific to ASD and mental retardation cases, including a de novo nonsense mutation and seven rare inherited changes. Our findings further link common genes between ASD and intellectual disability.
4. Blampied M, Johnston L, Miles L, Liberty K. {{Sensitivity to differences between enjoyment and non-enjoyment smiles in children with autism spectrum disorder}}. {Br J Dev Psychol} (Jun);28(Pt 2):483-489.
The sensitivity of male children (5-15 years) with and without autism spectrum disorder (ASD) to the affective state of others was tested using an emotion recognition task. Only children without ASD could reliably differentiate between enjoyment and non-enjoyment smiles. Results are considered in terms of the social impairments of children with ASD.
5. Bloom MS, Houston AS, Mills JL, Molloy CA, Hediger ML. {{Finger bone immaturity and 2D:4D ratio measurement error in the assessment of the hyperandrogenic hypothesis for the etiology of autism spectrum disorders}}. {Physiol Behav} (Jun 1);100(3):221-224.
Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of autism spectrum disorders (ASD). The ratios of the lengths of the bones of the 2nd to the 4th digit (2D:4D) are purported to be markers for prenatal androgen exposure and to be established early in gestation. Elongation of the 4th digit in response to testosterone is said to reduce 2D:4D in males versus females. We examined the ratios of bones from the left hand radiographs of 75 boys and 6 girls 4-8 years of age, diagnosed with ASD, to evaluate digit ratio as a marker for gestational androgen exposure. Contrary to our expectations, girls had reduced 2D:4D compared to boys but the difference was not significant (Cohen’s D 0.51-0.66, P>0.05). The limited sample size for this study and the absence of a referent group precluded providing robust estimates for girls and identifying possible statistical differences between the sexes. Tanner-Whitehouse 3 (TW3) rating of finger bone growth suggested relative immaturity of the 4th relative to the 2nd digits. Positive correlations were detected for 2D:4D ratios, body mass index (r=0.23, P=0.039), chronologic age (r=0.35, P=0.001), and skeletal age (r=0.42, P<0.0001). The TW3 ratings and associations between 2D:4D ratios and indicators of growth suggest that digits develop at different rates. This asynchronous development may produce differences in 2D:4D over time which could lead to erroneous interpretation of androgen exposure in utero among young ASD children.
6. Dias GG, Prado EF, Vadasz E, Siqueira JT. {{Evaluation of the efficacy of a dental plaque control program in autistic patients}}. {J Autism Dev Disord} (Jun);40(6):704-708.
The aim of this study was to verify the efficacy of a programme for dental plaque control in autistics. Patients were evaluated on five occasions over a period of 180 days using the following instruments: OHI-S, DMF-T, the Fonnes brushing technique and diet questionnaire. Participants were divided into two groups according to level of co-operation on the programme: Group A (co-operative) and Group B (non-cooperative). A statistically significant improvement (p < 0.001) in Oral Hygiene was attained, with 84.2% showing regular or satisfactory hygiene at study end-point. Conclusion: Groups A and B both showed improvement in hygiene (p < 0.001 and p = 0.004), but improvement was significantly higher among co-operative patients (p < 0.001 at 180 days), who also had a higher mean age (p = 0.02).
7. 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} (Jun);40(6):762-773.
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.
8. Fatemi SH, Reutiman TJ, Folsom TD, Rooney RJ, Patel DH, Thuras PD. {{mRNA and protein levels for GABAAalpha4, alpha5, beta1 and GABABR1 receptors are altered in brains from subjects with autism}}. {J Autism Dev Disord} (Jun);40(6):743-750.
We have shown altered expression of gamma-aminobutyric acid A (GABA(A)) and gamma-aminobutyric acid B (GABA(B)) receptors in the brains of subjects with autism. In the current study, we sought to verify our western blotting data for GABBR1 via qRT-PCR and to expand our previous work to measure mRNA and protein levels of 3 GABA(A) subunits previously associated with autism (GABRalpha4; GABRalpha5; GABRbeta1). Three GABA receptor subunits demonstrated mRNA and protein level concordance in superior frontal cortex (GABRalpha4, GABRalpha5, GABRbeta1) and one demonstrated concordance in cerebellum (GABBetaR1). These results provide further evidence of impairment of GABAergic signaling in autism.
9. Foss-Feig JH, Kwakye LD, Cascio CJ, Burnette CP, Kadivar H, Stone WL, Wallace MT. {{An extended multisensory temporal binding window in autism spectrum disorders}}. {Exp Brain Res} (Jun);203(2):381-389.
Autism spectrum disorders (ASD) form a continuum of neurodevelopmental disorders, characterized by deficits in communication and reciprocal social interaction, as well as by repetitive behaviors and restricted interests. Sensory disturbances are also frequently reported in clinical and autobiographical accounts. However, surprisingly few empirical studies have characterized the fundamental features of sensory and multisensory processing in ASD. The current study is structured to test for potential differences in multisensory temporal function in ASD by making use of a temporally dependent, low-level multisensory illusion. In this illusion, the presentation of a single flash of light accompanied by multiple sounds often results in the illusory perception of multiple flashes. By systematically varying the temporal structure of the audiovisual stimuli, a « temporal window » within which these stimuli are likely to be bound into a single perceptual entity can be defined. The results of this study revealed that children with ASD report the flash-beep illusion over an extended range of stimulus onset asynchronies relative to children with typical development, suggesting that children with ASD have altered multisensory temporal function. These findings provide valuable new insights into our understanding of sensory processing in ASD and may hold promise for the development of more sensitive diagnostic measures and improved remediation strategies.
10. Frye CA, Bloom MS, Wersinger S. {{Androgens, autism and more}}. {Physiol Behav} (Jun 1);100(3):197-198.
11. Frye CA, Llaneza DC. {{Corticosteroid and neurosteroid dysregulation in an animal model of autism, BTBR mice}}. {Physiol Behav} (Jun 1);100(3):264-267.
Autism spectrum disorders (ASD) are a constellation of neurodevelopmental disorders associated with disruptions in social, cognitive, and/or motor behaviors. ASD are more prevalent among males than females and characterized by aberrant social and language development, and a dysregulation in stress-responding. Levels of progesterone (P(4)) and its metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) are higher and more variable in females compared to males. 3alpha,5alpha-THP is also a neurosteroid, which can be rapidly produced de novo in the brain, independent of peripheral gland secretion, and can exert homeostatic effects to modulate stress-responding. An inbred mouse strain that has demonstrated an ASD-like behavioral and neuroendocrine phenotype is BTBR T +tf/J (BTBR). BTBR mice have deficits in cognitive and social behaviors and have high circulating levels of the stress hormone, corticosterone. We hypothesized that central 3alpha,5alpha-THP levels would be different among BTBR mice compared to mice on a similar background C57BL/6J (C57/J) and 129S1/SvlmJ (129S1). Tissues were collected from BTBR, C57/J and 129S1 male mice and levels of corticosterone, P(4), and 3alpha,5alpha-THP in plasma and in the hypothalamus, midbrain, hippocampus, and cerebellum were measured by radioimmunoassay. Circulating levels of corticosterone, P(4), and 3alpha,5alpha-THP were significantly higher among BTBR, than C57/J and 129S1, mice. Levels of P(4) in the cerebellum were significantly higher than other brain regions among all mouse strains. Levels of 3alpha,5alpha-THP in the hypothalamus of BTBR mice were significantly higher compared to C57/J and 129S1 mice. These findings suggest that neuroendocrine dysregulation among BTBR mice extends to 3alpha,5alpha-THP.
12. Gold R, Faust M, Goldstein A. {{Semantic integration during metaphor comprehension in Asperger syndrome}}. {Brain Lang} (Jun);113(3):124-134.
Previous research indicates severe disabilities in processing figurative language in people diagnosed on the autism spectrum disorders. However, this aspect of language comprehension in Asperger syndrome (AS) specifically has rarely been the subject of formal study. The present study aimed to examine the possibility that in addition to their pragmatic deficits, the difficulties in the comprehension of metaphors in AS may be explained by deficient linguistic information processing. Specifically, we aimed to examine whether a deficient semantic integration process underlies the difficulties in metaphor comprehension frequently experienced by persons with AS. The semantic integration process of sixteen AS participants and sixteen matched controls was examined using event related potentials (ERPs). N400 amplitude served as an index for degree of effort invested in the semantic integration process of two-word expressions denoting literal, conventional metaphoric, and novel metaphoric meaning, as well as unrelated word pairs. Large N400 amplitudes for both novel and conventional metaphors demonstrated the greater difficulties in metaphor comprehension in the AS participants as compared to controls. Findings suggest that differences in linguistic information processing cause difficulties in metaphor comprehension in AS.
13. Groen W, Teluij M, Buitelaar J, Tendolkar I. {{Amygdala and Hippocampus Enlargement During Adolescence in Autism}}. {J Am Acad Child Adolesc Psychiatry} (Jun);49(6):552-560.
OBJECTIVE: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse. METHOD: We measured amygdala and hippocampus volume in a homogeneous group of adolescents with autism (12 through18 years; n = 23) and compared them with an age-, sex-, and IQ-matched control group (n = 29) using a validated automated segmentation procedure in 1.5-T magnetic resonance images. All analyses were adjusted for total brain volume. RESULTS: Repeated-measures analysis revealed a significant group x hemisphere x brain structure interaction (p = .038), even when corrected for total brain volume. Post-hoc analysis showed that the right amygdala and left hippocampus were significantly enlarged (p = .010; p = .015) in the autism compared with the control group. There were no significant correlations between age and amygdala or hippocampus volume. CONCLUSIONS: The abnormal enlargement of the amygdala and hippocampus in adolescents with autism adds to previous findings of enlargement of these structures in children with autism. This may reflect increased activity of these structures and thereby altered emotion perception and regulation. Our results could therefore be interpreted in light of developmental adaptation of the autistic brain to a continuous overflow of emotional learning experiences.
14. Hobson RP, Lee A, Hobson JA. {{Personal pronouns and communicative engagement in autism}}. {J Autism Dev Disord} (Jun);40(6):653-664.
In three experimental conditions, we tested matched children with and without autism (n = 15 per group) for their comprehension and use of first person plural (‘we’) and third person singular (‘he’) pronouns, and examined whether such linguistic functioning related to their social interaction. The groups were indistinguishable in their comprehension and use of ‘we’ pronouns, although within each group, such usage was correlated with ratings of interpersonal connectedness with the collaborator. On the other hand, participants with autism were less likely to use third person pronouns or to show patterns of eye gaze reflecting engagement with an interlocutor’s stance vis-a-vis a third person. In these settings, atypical third person pronoun usage seemed to reflect limited communicative engagement, but first person pronouns were relatively spared.
15. Holland L, Low J. {{Do children with autism use inner speech and visuospatial resources for the service of executive control? Evidence from suppression in dual tasks}}. {Br J Dev Psychol} (Jun);28(Pt 2):369-391.
Three experiments used dual-task suppression methodology to study the use of inner speech and visuospatial resources for mediating central executive performance by children with autism (CWA) and group-matched typically developing (TD) controls. Expt 1 revealed that CWA did not recruit inner speech to facilitate arithmetic task-switching performance: there was no effect of articulatory suppression (AS) on completion time for CWA compared to the TD group. Expt 2 revealed that suppression of visuospatial resources disrupted the task-switching performance of both CWA and TD groups. It also confirmed that the task-switching performance of CWA was significantly slowed by visuospatial compared to AS. Expt 3 showed that CWA also did not employ inner speech, compared to visuospatial resources, for implementing planning movements. Overall, compared to the mixture of representations used by the TD group for problem solving, CWA seemed to use visuospatial working memory resources but not inner speech to service executive control.
16. Jarrold C, Mansergh R, Whiting C. {{The representational status of pretence: evidence from typical development and autism}}. {Br J Dev Psychol} (Jun);28(Pt 2):239-254.
The question of whether understanding pretend play requires meta-representational skill was examined among typically developing children and individuals with autism. Participants were presented with closely equated true and false pretence trials in which they had to judge a protagonist’s pretend reading of a situation, which either matched or differed from their own. Results showed that individuals’ theory of mind abilities determined their performance on false, but not true, pretence trials. These findings imply that meta-representation is involved when an individual has to make sense of a pretend state of mind that differs from their own, but, crucially, they also show that pretend play can often be understood without meta-representational competence.
17. Kantojarvi K, Onkamo P, Vanhala R, Alen R, Hedman M, Sajantila A, Nieminen-von Wendt T, Jarvela I. {{Analysis of 9p24 and 11p12-13 regions in autism spectrum disorders: rs1340513 in the JMJD2C gene is associated with ASDs in Finnish sample}}. {Psychiatr Genet} (Jun);20(3):102-108.
OBJECTIVE: Autism spectrum disorders (ASD) often show obsessive repetitive symptoms that are characteristic to obsessive-compulsive disorder (OCD). Aberrant glutamate function has been suggested to a risk for both ASDs and OCD. Considering the common metabolic pathway and recent results from association studies both in OCD and ASDs, a question, whether there is common molecular background in ASDs and OCD, was raised. METHODS: Ten single nucleotide polymorphisms (SNPs) at 9p24 and 11p12-p13 containing glutamate transporter genes SLC1A1 and SLC1A2 and their neighboring regions in 175 patients with ASDs and 216 controls of Finnish origin were analyzed using real-time-PCR or direct sequencing. RESULTS: The strongest association was detected with rs1340513 in the JMJD2C gene at 9p24.1 (P=0.007; corrected P=0.011) that is the same SNP associated with infantile autism (P=0.0007) in the autism genome project consortium (2007). No association was detected at 11p12-p13 with ASD. Interestingly, the strongest association in OCD has been found at rs301443 (P=0.000067) residing between SLC1A1 and JMJD2C at 9p24. CONCLUSION: In summary, our results give evidence for a possible common locus for OCD and ASDs at 9p24. We speculate that the area may represent a special candidate region for obsessive repetitive symptoms in ASDs.
18. Kuhlthau K, Orlich F, Hall TA, Sikora D, Kovacs EA, Delahaye J, Clemons TE. {{Health-Related Quality of Life in children with autism spectrum disorders: results from the autism treatment network}}. {J Autism Dev Disord} (Jun);40(6):721-729.
We examined data collected as a part of the Autism Treatment Network, a group of 15 autism centers across the United States and Canada. Mean Health-Related Quality of Life (HRQoL) scores of the 286 children assessed were significantly lower than those of healthy populations (according to published norms). When compared to normative data from children with chronic conditions, children with ASD demonstrated worse HRQoL for total, psychosocial, emotional and social functioning, but did not demonstrate differing scores for physical and school functioning. HRQoL was not consistently related to ASD diagnosis or intellectual ability. However, it was consistently related to internalizing and externalizing problems as well as repetitive behaviors, social responsiveness, and adaptive behaviors. Associations among HRQoL and behavioral characteristics suggest that treatments aimed at improvements in these behaviors may improve HRQoL.
19. Leonard H, Downs J, Jian L, Bebbington A, Jacoby P, Nagarajan L, Ravine D, Woodhead H. {{Valproate and risk of fracture in Rett syndrome}}. {Arch Dis Child} (Jun);95(6):444-448.
OBJECTIVES: Some associations between antiepileptic drugs (AEDs) and fracture risk have been reported in the general population. This study investigated the relationships between fracture risk and commonly used AEDs in Rett syndrome, a genetic disorder associated with intellectual and physical disability. STUDY DESIGN: Cases (n=233) were sourced from the population-based Australian Rett Syndrome Database and longitudinal data were used. The Cox proportional hazard model was used to analyse relationships between fracture and prescribed AEDs, mobility, epilepsy diagnosis and genotype. RESULTS: After controlling for mobility, epilepsy diagnosis and genotype, use of valproate increased the risk of fracture threefold after at least 1 year (HR 3.56; 95% CI 1.85 to 6.82) and after 2 or more years (HR 3.02; 95% CI 1.90 to 4.80). There was a lesser increased risk (HR 1.99; 95% CI 0.99 to 4.02) with lamotrigine in the first year of use but not for subsequent years of use. Carbamazepine slightly decreased the risk (HR 0.60; 95% CI 0.35 to 1.02) after 2 or more years of use. CONCLUSIONS: The effect of valproate on bone health should be considered when managing epilepsy in Rett syndrome. Multiple mechanisms could be contributing to this effect.
20. Li X, Hu Z, He Y, Xiong Z, Long Z, Peng Y, Bu F, Ling J, Xun G, Mo X, Pan Q, Zhao J, Xia K. {{Association analysis of CNTNAP2 polymorphisms with autism in the Chinese Han population}}. {Psychiatr Genet} (Jun);20(3):113-117.
OBJECTIVES: Autism is a neurodevelopmental disorder, and genetic factors play an important role in its pathogenesis. Earlier findings suggest the CNTNAP2 as a predisposition locus of autism, but no study has been carried out on the possible association of CNTNAP2 with autism in the Chinese Han population. METHODS: In this study, three single nucleotide polymorphisms located within the CNTNAP2 were genotyped in 185 Chinese Han autistic families by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by a transmission disequilibrium test. RESULTS: The results show that a common noncoding variant (rs10500171) is associated with the increased risk for autism, and haplotype T-A (rs7794745- rs10500171, P=0.011) and haplotype A-T-A (rs10244837- rs7794745- rs10500171, P=0.032) also showed evidence of association. CONCLUSION: The results of family-based association study suggested that the CNTNAP2 is a susceptibility gene of autism in the Chinese Han population.
21. Llaneza DC, DeLuke SV, Batista M, Crawley JN, Christodulu KV, Frye CA. {{Communication, interventions, and scientific advances in autism: a commentary}}. {Physiol Behav} (Jun 1);100(3):268-276.
Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger Syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its co-morbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research.
22. Loth E, Happe F, Gomez JC. {{Variety is not the spice of life for people with autism spectrum disorders: frequency ratings of central, variable and inappropriate aspects of common real-life events}}. {J Autism Dev Disord} (Jun);40(6):730-742.
This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in this type of situation. The ASD boys made significantly more errors than the typically developing boys in rating the occurrences of variable aspects. In both groups, ratings of variable aspects were age-related, but in the ASD boys, they were also related to theory of mind and weak coherence test scores, and to severity of autistic symptoms. Implications for the understanding of some repetitive behaviours, such as the tendency to adhere to inflexible routines, are discussed.
23. Main PA, Angley MT, Thomas P, O’Doherty CE, Fenech M. {{Folate and methionine metabolism in autism: a systematic review}}. {Am J Clin Nutr} (Jun);91(6):1598-1620.
BACKGROUND: Autism is a complex neurodevelopmental disorder that is increasingly being recognized as a public health issue. Recent evidence has emerged that children with autism may have altered folate or methionine metabolism, which suggests the folate-methionine cycle may play a key role in the etiology of autism. OBJECTIVE: The objective was to conduct a systematic review to examine the evidence for the involvement of alterations in folate-methionine metabolism in the etiology of autism. DESIGN: A systematic literature review was conducted of studies reporting data for metabolites, interventions, or genes of the folate-methionine pathway in autism. Eighteen studies met the inclusion criteria, 17 of which provided data on metabolites, 5 on interventions, and 6 on genes and their related polymorphisms. RESULTS: The findings of the review were conflicting. The variance in results can be attributed to heterogeneity between subjects with autism, sampling issues, and the wide range of analytic techniques used. Most genetic studies were inadequately powered to provide more than an indication of likely genetic relations. CONCLUSIONS: The review concluded that further research is required with appropriately standardized and adequately powered study designs before any definitive conclusions can be made about the role for a dysfunctional folate-methionine pathway in the etiology of autism. There is also a need to determine whether functional benefits occur when correcting apparent deficits in folate-methionine metabolism in children with autism.
24. Mak WW, Kwok YT. {{Internalization of stigma for parents of children with autism spectrum disorder in Hong Kong}}. {Soc Sci Med} (Jun);70(12):2045-2051.
An attribution model was tested to explain the internalization of stigma among parents of children with Autism Spectrum Disorder (ASD). In the model, the internalization paths from courtesy stigma to affiliate stigma and the impact of three types of social support on affiliate stigma and psychological well-being were examined. The study was conducted in Hong Kong, China; one hundred and eighty-eight parents of children with ASD were recruited to complete the questionnaire. The model showed excellent fit to the data. Path analysis suggested three possible paths of internalizing courtesy stigma, including the direct path to affiliate stigma, through perceived controllability, or through perceived responsibility and self-blame. Support from family, significant others, friends, or professionals was found to be related to affiliate stigma and psychological well-being differentially. The internalization of stigma among parents of ASD children was severe. The path model sheds light on possible ways to reduce stigma in future services.
25. Messer A. {{Mini-review: polybrominated diphenyl ether (PBDE) flame retardants as potential autism risk factors}}. {Physiol Behav} (Jun 1);100(3):245-249.
Brominated flame retardants, including Polybrominated diphenyl ethers (PBDEs) have been used at increasing levels in home furnishings and electronics over the past 25 years. They have also become widespread environmental pollutants. High PBDE levels have been detected in food, household dust, and indoor air, with subsequent appearance in animal and human tissues. This minireview summarizes studies on the extent to which these compounds can act as potent thyroid hormone mimetics, and emerging studies on long-term neurological effects of acute administration of PBDEs during development. When these data are considered in combination with the extensive literature on stage-dependent effects of thyroid hormone on aspects of brain development that are also implicated in autistic brains, a hypothesis that PBDEs might also serve as autism risk factors emerges. Studies designed to explicitly test this hypothesis will require chronic exposure paradigms, and specific body burden and behavioral monitoring in animal models. Such testing may help to prioritize extensive human epidemiological studies, as well as offer protocols for evaluation of future compounds.
26. Munesue T, Yokoyama S, Nakamura K, Anitha A, Yamada K, Hayashi K, Asaka T, Liu HX, Jin D, Koizumi K, Islam MS, Huang JJ, Ma WJ, Kim UH, Kim SJ, Park K, Kim D, Kikuchi M, Ono Y, Nakatani H, Suda S, Miyachi T, Hirai H, Salmina A, Pichugina YA, Soumarokov AA, Takei N, Mori N, Tsujii M, Sugiyama T, Yagi K, Yamagishi M, Sasaki T, Yamasue H, Kato N, Hashimoto R, Taniike M, Hayashi Y, Hamada J, Suzuki S, Ooi A, Noda M, Kamiyama Y, Kido MA, Lopatina O, Hashii M, Amina S, Malavasi F, Huang EJ, Zhang J, Shimizu N, Yoshikawa T, Matsushima A, Minabe Y, Higashida H. {{Two genetic variants of CD38 in subjects with autism spectrum disorder and controls}}. {Neurosci Res} (Jun);67(2):181-191.
The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p<0.040) and rs3796863 (p<0.005) showed significant associations with a subset of ASD (IQ>70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD.
27. Newman C, Cashin A, Waters CD. {{A modified hermeneutic phenomenological approach toward individuals who have autism}}. {Res Nurs Health} (Jun);33(3):265-271.
Individuals with autism have a unique cognitive processing style characterized by impaired abstraction, impaired theory of mind, and visual as opposed to linguistic processing of information. A consequence of this unique cognitive processing style is that traditional ways of hermeneutical phenomenological examination may be inadequate to achieve the kind of understanding of experience toward which this method is directed. In order to stay true to Heidegger’s hermeneutic phenomenology, we needed to develop modifications to this research methodology, which include the use of visual aids to promote participant engagement and access the eidetic memory of a participant with autism, so as to elicit concrete descriptors of an experience.
28. Qiu A, Adler M, Crocetti D, Miller MI, Mostofsky SH. {{Basal Ganglia Shapes Predict Social, Communication, and Motor Dysfunctions in Boys With Autism Spectrum Disorder}}. {J Am Acad Child Adolesc Psychiatry} (Jun);49(6):539-551 e534.
OBJECTIVE: Basal ganglia abnormalities have been suggested as contributing to motor, social, and communicative impairments in autism spectrum disorder (ASD). Volumetric analyses offer limited ability to detect localized differences in basal ganglia structure. Our objective was to investigate basal ganglia shape abnormalities and their association with behavioral features of ASD, which may involve multiple frontal-subcortical circuits. METHOD: Basal ganglia were manually delineated from MR images of 32 boys with ASD and 45 typically developing (TD) boys. Large deformation diffeomorphic metric mapping (LDDMM) was used to assess between-group differences in basal ganglia shape and to examine associations with motor, praxis, and reciprocal social and communicative impairments in ASD. RESULTS: Boys with ASD showed changes in right basal ganglia shape as compared with TD boys; surface deformation was present in the caudate, putamen, and globus pallidus but did not stand up to correction for multiple comparisons. Brain-behavior correlation findings were more robust; analyses accounting for multiple comparisons revealed, in boys with ASD, surface inward deformation of the right posterior putamen predicted poorer motor skill, whereas surface inward deformation of the bilateral anterior and posterior putamen predicted poorer praxis. Surface outward deformation in the bilateral medial caudate head predicted greater reciprocal social and communicative impairment. CONCLUSIONS: Motor, social, and communicative impairments in boys with ASD are associated with shape abnormalities in the basal ganglia. The findings suggest abnormalities within parallel frontal-subcortical circuits are differentially associated with impaired acquisition of motor and reciprocal social and communicative skills in ASD.
29. Raznahan A, Toro R, Daly E, Robertson D, Murphy C, Deeley Q, Bolton PF, Paus T, Murphy DG. {{Cortical anatomy in autism spectrum disorder: an in vivo MRI study on the effect of age}}. {Cereb Cortex} (Jun);20(6):1332-1340.
There is increasing evidence that children with autism spectrum disorder (ASD) have age-related differences from controls in cortical volume (CV). It is less clear, however, if these persist in adulthood and whether these reflect alterations in cortical thickness (CT) or cortical surface area (SA). Hence, we used magnetic resonance imaging to investigate the relationship between age and CV, CT, and SA in 127 males aged 10 through 60 years (76 with ASD and 51 healthy controls). « Regional » analyses (using cortical parcellation) identified significant age-by-group interactions in both CV and CT (but not SA) in the temporal lobes and within these the fusiform and middle temporal gyri. Spatially nonbiased « vertex-based » analysis replicated these results and identified additional « age-by-group » interactions for CT within superior temporal, inferior and medial frontal, and inferior parietal cortices. Here, CV and CT were 1) significantly negatively correlated with age in controls, but not in ASD, and 2) smaller in ASD than controls in childhood but vice versa in adulthood. Our findings suggest that CV dysmaturation in ASD extends beyond childhood, affects brain regions crucial to social cognition and language, and is driven by CT dysmaturation. This may reflect primary abnormalities in cortical plasticity and/or be secondary to disturbed interactions between individuals with ASD and their environment.
30. Schaevitz LR, Moriuchi JM, Nag N, Mellot TJ, Berger-Sweeney J. {{Cognitive and social functions and growth factors in a mouse model of Rett syndrome}}. {Physiol Behav} (Jun 1);100(3):255-263.
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 memories, 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 the 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.
31. Shaw W. {{Increased urinary excretion of a 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), an abnormal phenylalanine metabolite of Clostridia spp. in the gastrointestinal tract, in urine samples from patients with autism and schizophrenia}}. {Nutr Neurosci} (Jun);13(3):135-143.
A compound identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) was found in higher concentrations in urine samples of children with autism compared to age and sex appropriate controls and in an adult with recurrent diarrhea due to Clostridium difficile infections. The highest value measured in urine samples was 7500 mmol/mol creatinine, a value 300 times the median normal adult value, in a patient with acute schizophrenia during an acute psychotic episode. The psychosis remitted after treatment with oral vancomycin with a concomitant marked decrease in HPHPA. The source of this compound appears to be multiple species of anaerobic bacteria of the Clostridium genus. The significance of this compound is that it is a probable metabolite of m-tyrosine (3-hydroxyphenylalanine), a tyrosine analog which depletes brain catecholamines and causes symptoms of autism (stereotypical behavior, hyperactivity, and hyper-reactivity) in experimental animals.
32. Silverman LB, Bennetto L, Campana E, Tanenhaus MK. {{Speech-and-gesture integration in high functioning autism}}. {Cognition} (Jun);115(3):380-393.
This study examined iconic gesture comprehension in autism, with the goal of assessing whether cross-modal processing difficulties impede speech-and-gesture integration. Participants were 19 adolescents with high functioning autism (HFA) and 20 typical controls matched on age, gender, verbal IQ, and socio-economic status (SES). Gesture comprehension was assessed via quantitative analyses of visual fixations during a video-based task, using the visual world paradigm. Participants’ eye movements were recorded while they watched videos of a person describing one of four shapes shown on a computer screen, using speech-and-gesture or speech-only descriptions. Participants clicked on the shape that the speaker described. Since gesture naturally precedes speech, earlier visual fixations to the target shape during speech-and-gesture compared to speech-only trials, would suggest immediate integration of auditory and visual information. Analyses of eye movements supported this pattern in control participants but not in individuals with autism: iconic gestures facilitated comprehension in typical individuals, while it hindered comprehension in those with autism. Cross-modal processing difficulties in autism were not accounted for by impaired unimodal speech or gesture processing. The results have important implications for the treatment of children and adults with this disorder.
33. Slayton RL. {{Autism spectrum disorder (ASD) may lead to lower prevalence and severity of dental caries than in children without ASD}}. {J Evid Based Dent Pract} (Jun);10(2):105-106.
ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: The caries experience and behavior of dental patients with autism spectrum disorder. Loo CY, Graham RM, Hughes CV. J Am Dent Assoc 2008;139(11):1518-24. REVIEWER: Rebecca L. Slayton, DDS, PhD PURPOSE/QUESTION: What is the caries experience and behavior of children with autism spectrum disorder compared with children without this disorder? SOURCE OF FUNDING: Information not available TYPE OF STUDY/DESIGN: Cross-sectional study (chart review) LEVEL OF EVIDENCE: Level 3: Other evidence STRENGTH OF RECOMMENDATION GRADE: Not applicable.
34. Sokhadze E, Baruth J, Tasman A, Mansoor M, Ramaswamy R, Sears L, Mathai G, El-Baz A, Casanova MF. {{Low-frequency repetitive transcranial magnetic stimulation (rTMS) affects event-related potential measures of novelty processing in autism}}. {Appl Psychophysiol Biofeedback} (Jun);35(2):147-161.
In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37-51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.
35. State MW. {{Another piece of the autism puzzle}}. {Nat Genet} (Jun);42(6):478-479.
A new study has identified rare de novo mutations in SHANK2 in individuals with autism and/or mental retardation. SHANK2 encodes a scaffolding protein present in excitatory synapses. This finding sheds some light on the pathophysiology of social and cognitive disability.
36. Virues-Ortega J. {{Applied behavior analytic intervention for autism in early childhood: meta-analysis, meta-regression and dose-response meta-analysis of multiple outcomes}}. {Clin Psychol Rev} (Jun);30(4):387-399.
A number of clinical trials and single-subject studies have been published measuring the effectiveness of long-term, comprehensive applied behavior analytic (ABA) intervention for young children with autism. However, the overall appreciation of this literature through standardized measures has been hampered by the varying methods, designs, treatment features and quality standards of published studies. In an attempt to fill this gap in the literature, state-of-the-art meta-analytical methods were implemented, including quality assessment, sensitivity analysis, meta-regression, dose-response meta-analysis and meta-analysis of studies of different metrics. Results suggested that long-term, comprehensive ABA intervention leads to (positive) medium to large effects in terms of intellectual functioning, language development, acquisition of daily living skills and social functioning in children with autism. Although favorable effects were apparent across all outcomes, language-related outcomes (IQ, receptive and expressive language, communication) were superior to non-verbal IQ, social functioning and daily living skills, with effect sizes approaching 1.5 for receptive and expressive language and communication skills. Dose-dependant effect sizes were apparent by levels of total treatment hours for language and adaptation composite scores. Methodological issues relating ABA clinical trials for autism are discussed.
37. Wegiel J, Kuchna I, Nowicki K, Imaki H, Wegiel J, Marchi E, Ma SY, Chauhan A, Chauhan V, Bobrowicz TW, de Leon M, Louis LA, Cohen IL, London E, Brown WT, Wisniewski T. {{The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes}}. {Acta Neuropathol} (Jun);119(6):755-770.
Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4-60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-mum-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype.
38. Wong VC, Kwan QK. {{Randomized controlled trial for early intervention for autism: a pilot study of the Autism 1-2-3 Project}}. {J Autism Dev Disord} (Jun);40(6):677-688.
We piloted a 2-week « Autism-1-2-3 » early intervention for children with autism and their parents immediately after diagnosis that targeted at (1) eye contact, (2) gesture and (3) vocalization/words. Seventeen children were randomized into the Intervention (n = 9) and Control (n = 8) groups. Outcome measures included the Autism Diagnostic Observation Schedule, Ritvo-Freeman Real Life Rating Scale, Symbolic Play Test, and Parenting Stress Index. Children with autism improved in language/communication, reciprocal social interaction, and symbolic play. Parents perceived significant improvement in their children’s language, social interaction, and their own stress level. This intervention can serve as short-term training on communication and social interaction for children with autism, and reduce the stress of their parents during the long waiting time for public health services.
39. Yorbik O, Kurt I, Hasimi A, Ozturk O. {{Chromium, cadmium, and lead levels in urine of children with autism and typically developing controls}}. {Biol Trace Elem Res} (Jun);135(1-3):10-15.
Although potentially harmful effects of heavy metals are well known, limited numbers of studies exist regarding their relationship with autism. The aim of this study was to investigate urine levels of some heavy metals such as of chromium (Cr), cadmium (Cd), and lead (Pb) in children with autism and healthy subjects. Urine levels of Cr, Cd, and Pb were measured by atomic absorption spectrometry in 30 children with autism and compared with 20 healthy controls. Urine Cd and Pb levels were found as significantly decreased in children with autism compared to healthy subjects (p < 0.05). On the other hand, urine Cr levels were significantly higher in children with autism than healthy subjects (p < 0.05). This study suggested that autism may be associated with significant decrease in excretion rate of Cd and Pb and a significant increase excretion rate in the levels of Cr in the urine. These results have indicated that further studies are warranted for investigation of possible roles of heavy metals in autism.
