1. Allen-Brady K, Cannon D, Robison R, McMahon WM, Coon H. {{A unified theory of autism revisited: linkage evidence points to chromosome X using a high-risk subset of AGRE families}}. {Autism Res} (Apr);3(2):47-52.
Zhao et al. [2007] in their « Unified Theory of Autism » hypothesized that incidence of autism in males could be explained by essentially two types of family structures: majority of autism cases are from low-risk autism families with de novo mutations, and a minority of cases are from high-risk multiplex families, where risk to male offspring approximates 50% consistent with a dominant model and high penetrance. Using the Autism Genetic Resource Exchange (AGRE) data set, Zhao et al. identified 86 high-risk families with likely dominant transmission. As genotype data are now available for many members of the AGRE resource, the objective of this manuscript was to determine if dominant linkage evidence for an autism predisposition gene exists in these 86 high-risk families. HumanHap550K Illumina SNP data were available for 92% of 455 total family members in these 86 high-risk families. We performed a linkage analysis using a pruned subset of markers where markers in high linkage disequilibrium were removed. We observed a single suggestive peak (maximum LOD 2.01, maximum HLOD 2.08) under a dominant model on chromosome Xp22.11-p21.2 that encompasses the IL1RAPL1 gene. Mutations or deletions in IL1RAPL1 have been previously reported in three families with autism. In our study, 11 families contributed nominally (P<0.05, HLOD>0.588) to the chromosome X peak. These results demonstrate that identification of a more homogeneous subset of autism cases, which was based on family structure in this study, may help to identify, localize and further our understanding of autism predisposition genes.
2. Baker J, Haltigan JD, Messinger DS. {{Non-Expert Ratings of Infant and Parent Emotion: Concordance with Expert Coding and Relevance to Early Autism Risk}}. {Int J Behav Dev} (Jan 1);34(1):88-95.
This study investigated a novel approach to obtaining data on parent and infant emotion during the Face-to-Face/Still-Face paradigm, and examined these data in light of previous findings regarding early autism risk. One-hundred and eighty eight non-expert students rated 38 parents and infant siblings of children who did (20) or did not (18) have autism spectrum disorders. Ratings averaged across 10 non-experts exhibited high concordance with expert facial-action codes for infant emotion, and 20 non-experts were required for reliable parent ratings. Findings replicated the well-established still-face effect and identified subtle risk associations consonant with results from previous investigations. The unique information offered by intuitive non-expert ratings is discussed as an alternative to complex and costly behavioral coding systems.
3. Best CA, Minshew NJ, Strauss MS. {{Gender discrimination of eyes and mouths by individuals with autism}}. {Autism Res} (Apr);3(2):88-93.
Evidence remains mixed about whether individuals with autism look less to eyes and whether they look more at mouths. Few studies have examined how spontaneous attention to facial features relates to face processing abilities. This study tested the ability to discriminate gender from facial features, namely eyes and mouths, by comparing accuracy scores of 17 children with autism and 15 adults with autism to 17 typically developing children and 15 typically developing adults. Results indicated that all participants regardless of diagnosis discriminated gender more accurately from eyes than from mouths. However, results indicated that compared to adults without autism, adults with autism were significantly worse at discriminating gender from eyes.
4. Bonnel A, McAdams S, Smith B, Berthiaume C, Bertone A, Ciocca V, Burack JA, Mottron L. {{Enhanced Pure-Tone Pitch Discrimination among Persons with Autism but not Asperger Syndrome}}. {Neuropsychologia} (Apr 27)
Persons with Autism Spectrum Disorders (ASD) display atypical perceptual processing in visual and auditory tasks. In vision, Bertone et al. (2005) found that enhanced and diminished visual processing is linked to the level of neural complexity required to process stimuli, as proposed in the neural complexity hypothesis. Based on these findings, Samson et al. (2006) proposed to extend the neural complexity hypothesis to the auditory modality. They hypothesized that persons with ASD should display enhanced performance for simple tones that are processed in primary auditory cortical regions, but diminished performance for complex tones that require additional processing in associative auditory regions, in comparison to typically developing individuals. To assess this hypothesis, we designed four auditory discrimination experiments targeting pitch, non-vocal and vocal timbre, and loudness. Stimuli consisted of spectro-temporally simple and complex tones. The participants were adolescents and young adults with autism, Asperger syndrome, and typical developmental histories, all with IQs in the normal range. Consistent with the neural complexity hypothesis and enhanced perceptual functioning model of ASD (Mottron et al., 2006), the participants with autism, but not with Asperger syndrome, displayed enhanced pitch discrimination for simple tones. However, no discrimination-thresholds differences were found between the participants with ASD and the typically developing persons across spectrally and temporally complex conditions. These findings indicate that enhanced pure-tone pitch discrimination may be a cognitive correlate of speech-delay among persons with ASD. However, auditory discrimination among this group does not appear to be directly contingent on the spectro-temporal complexity of the stimuli.
5. Boyd BA, Baranek GT, Sideris J, Poe MD, Watson LR, Patten E, Miller H. {{Sensory features and repetitive behaviors in children with autism and developmental delays}}. {Autism Res} (Apr);3(2):78-87.
This study combined parent and observational measures to examine the association between aberrant sensory features and restricted, repetitive behaviors in children with autism (N=67) and those with developmental delays (N=42). Confirmatory factor analysis was used to empirically validate three sensory constructs of interest: hyperresponsiveness, hyporesponsiveness, and sensory seeking. Examining the association between the three derived sensory factor scores and scores on the Repetitive Behavior Scales–Revised revealed the co-occurrence of these behaviors in both clinical groups. Specifically, high levels of hyperresponsive behaviors predicted high levels of repetitive behaviors, and the relationship between these variables remained the same controlling for mental age. We primarily found non-significant associations between hyporesponsiveness or sensory seeking and repetitive behaviors, with the exception that sensory seeking was associated with ritualistic/sameness behaviors. These findings suggest that shared neurobiological mechanisms may underlie hyperresponsive sensory symptoms and repetitive behaviors and have implications for diagnostic classification as well as intervention.
6. Curtis JT, Hood AN, Chen Y, Cobb GP, Wallace DR. {{Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: An animal model of autism}}. {Behav Brain Res} (Apr 28)
We examined the effects of chronic metals ingestion on social behavior in the normally highly social prairie vole to test the hypothesis that metals may interact with central dopamine systems to produce the social withdrawal characteristic of autism. Relative to water-treated controls, 10 weeks of chronic ingestion of either Hg(++) or Cd(++) via drinking water significantly reduced social contact by male voles when they were given a choice between isolation or contact with an unfamiliar same-sex conspecific. The effects of metals ingestion were specific to males: no effects of metals exposure were seen in females. Metals ingestion did not alter behavior of males allowed to choose between isolation or their familiar cage-mates, rather than strangers. We also examined the possibility that metals ingestion affects central dopamine functioning by testing the voles’ locomotor responses to peripheral administration of amphetamine. As with the social behavior, we found a sex-specific effect of metals on amphetamine responses. Males that consumed Hg(++) did not increase their locomotor activity in response to amphetamine, whereas similarly treated females and males that ingested only water significantly increased their locomotor activities. Thus, an ecologically relevant stimulus, metals ingestion, produced two of the hallmark characteristics of autism – social avoidance and a male-oriented bias. These results suggest that metals exposure may contribute to the development of autism, possibly by interacting with central dopamine function, and support the use of prairie voles as a model organism in which to study autism.
7. Ghanizadeh A. {{Can Retaining Asperger Syndrome in DSM V Help Establish Neurobiological Endophenotypes?}}. {J Autism Dev Disord} (May 1)
8. Kelemenova S, Schmidtova E, Ficek A, Celec P, Kubranska A, Ostatnikova D. {{Polymorphisms of candidate genes in Slovak autistic patients}}. {Psychiatr Genet} (Apr 29)
Autism is one of the most genetically influenced neuropsychiatric disorders. However, its detailed genetic basis is far from being clear. Genome-wide association studies have revealed a number of candidate genes, mostly related to synaptogenesis and various neuroendocrine pathways. In our study we have focused on oxytocin (OT), oxytocin receptor (OXTR), GABA receptor gamma 3 (GABRG3), neuroligin (NLGN4X), and reelin (RELN). After signed consent, 90 autistic boys and 85 healthy controls were enrolled in the study. Polymorphisms of OT (rs2740204), OXTR (rs2228485), GABRG3 (rs28431127), and NLGN4X (rs5916338) were analyzed using restriction fragment length polymorphism. (GGC)n STR polymorphism in the 5′ UTR of the RELN gene was genotyped using fragment analysis. The only significant association in autistic boys in Slovakia was found with higher number of GGC repeats in the RELN gene (P=0.001) potentially explaining lower RELN levels in blood and brain of autistic patients.
9. Lazar AS, Lazar ZI, Biro A, Gyori M, Tarnok Z, Prekop C, Keszei A, Stefanik K, Gadoros J, Halasz P, Bodizs R. {{Reduced fronto-cortical brain connectivity during NREM sleep in Asperger syndrome: An EEG spectral and phase coherence study}}. {Clin Neurophysiol} (Apr 28)
OBJECTIVE: To investigate whether sleep macrostructure and EEG power spectral density and coherence during NREM sleep are different in Asperger syndrome (AS) compared to typically developing children and adolescents. METHODS: Standard all night EEG sleep parameters were obtained from 18 un-medicated subjects with AS and 14 controls (age range: 7.5-21.5years) after one adaptation night. Spectral, and phase coherence measures were computed for multiple frequency bands during NREM sleep. RESULTS: Sleep latency and wake after sleep onset were increased in AS. Absolute power spectrum density (PSD) was significantly reduced in AS in the alpha, sigma, beta and gamma bands and in all 10 EEG derivations. Relative PSD showed a significant increase in delta and a decrease in the sigma band for frontal, and in beta for centro-temporal derivations. Intrahemispheric coherence measures were markedly lower in AS in the frontal areas, and the right hemisphere over all EEG channels. The most prominent reduction in intrahemispheric coherence was observed over the fronto-central areas in delta, theta, alpha and sigma EEG frequency bands. CONCLUSION: EEG power spectra and coherence during NREM sleep, in particular in fronto-cortical derivations are different in AS compared to typically developing children and adolescents. SIGNIFICANCE: Quantitative analysis of the EEG during NREM sleep supports the hypothesis of frontal dysfunction in AS.
10. Limperopoulos C. {{Extreme prematurity, cerebellar injury, and autism}}. {Semin Pediatr Neurol} (Mar);17(1):25-29.
11. Minjarez MB, Williams SE, Mercier EM, Hardan AY. {{Pivotal Response Group Treatment Program for Parents of Children with Autism}}. {J Autism Dev Disord} (May 4)
The number of children diagnosed with autism spectrum disorders is increasing, necessitating the development of efficient treatment models. Research has demonstrated that parent-delivered behavioral interventions are a viable treatment model; however, little research has focused on teaching parents in groups. The aim of this study was to demonstrate that parents can learn Pivotal Response Training (PRT) in group therapy, resulting in correlated gains in children’s language. Baseline and post-treatment data were obtained and examined for changes in (a) parent fidelity of PRT implementation, and (b) child functional verbal utterances. Significant differences were observed for both variables. These findings suggest that parents can learn PRT in a group format, resulting in correlated child language gains, thus future controlled studies are warranted.
12. 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} (Apr 30)
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.
13. Oosterling I, Visser J, Swinkels S, Rommelse N, Donders R, Woudenberg T, Roos S, van der Gaag RJ, Buitelaar J. {{Randomized Controlled Trial of the Focus Parent Training for Toddlers with Autism: 1-Year Outcome}}. {J Autism Dev Disord} (May 4)
This randomized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone. The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al. (Eur Child Adolesc Psychiatr 11:266-272, 2002). Seventy-five toddlers with autism spectrum disorder (65 autism, 10 PDD-NOS, mean age = 34.4 months, SD = 6.2) were enrolled. Analyses were conducted on a final sample of 67 children (lost to follow-up = 8). No significant intervention effects were found for any of the primary (language), secondary (global clinical improvement), or mediating (child engagement, early precursors of social communication, or parental skills) outcome variables, suggesting that the ‘Focus parent training’ was not of additional value to the more general care-as-usual.
14. Puzzo I, Cooper NR, Vetter P, Russo R. {{EEG activation differences in the pre-motor cortex and supplementary motor area between normal individuals with high and low traits of autism}}. {Brain Res} (Apr 29)
The human mirror neurons system (hMNS) is believed to provide a basic mechanism for social cognition. Event related desynchronization (ERD) in alpha (8-12Hz) & low beta band (12-20Hz) over sensori-motor cortex has been suggested to index mirror neurons’ activity. We tested whether autistic traits revealed by high and low scores on the Autistic Quotient (AQ) in the normal population are linked to variations in the electroencephalogram (EEG) over motor, pre-motor cortex and supplementary motor area (SMA) during action observation. Results revealed that in the low AQ group, the pre-motor cortex and SMA were more active during hand action than static hand observation whereas in the high AQ group the same areas were active both during static and hand action observation. In fact participants with high traits of autism showed greater low beta ERD while observing the static hand than those with low traits and this low beta ERD was not significantly different when they watched hand actions. Over primary motor cortex, the classical alpha and low beta ERD during hand actions relative to static hand observation was found across all participants. These findings suggest that the observation-execution matching system works differently according to the degree of autism traits in the normal population and that this is differentiated in terms of the EEG according to scalp site and bandwidth.
15. Scott-Van Zeeland AA, Dapretto M, Ghahremani DG, Poldrack RA, Bookheimer SY. {{Reward processing in autism}}. {Autism Res} (Apr);3(2):53-67.
The social motivation hypothesis of autism posits that infants with autism do not experience social stimuli as rewarding, thereby leading to a cascade of potentially negative consequences for later development. While possible downstream effects of this hypothesis such as altered face and voice processing have been examined, there has not been a direct investigation of social reward processing in autism. Here we use functional magnetic resonance imaging to examine social and monetary rewarded implicit learning in children with and without autism spectrum disorders (ASD). Sixteen males with ASD and sixteen age- and IQ-matched typically developing (TD) males were scanned while performing two versions of a rewarded implicit learning task. In addition to examining responses to reward, we investigated the neural circuitry supporting rewarded learning and the relationship between these factors and social development. We found diminished neural responses to both social and monetary rewards in ASD, with a pronounced reduction in response to social rewards (SR). Children with ASD also demonstrated a further deficit in frontostriatal response during social, but not monetary, rewarded learning. Moreover, we show a relationship between ventral striatum activity and social reciprocity in TD children. Together, these data support the hypothesis that children with ASD have diminished neural responses to SR, and that this deficit relates to social learning impairments.
16. Travers BG, Klinger MR, Mussey JL, Klinger LG. {{Motor-linked implicit learning in persons with autism spectrum disorders}}. {Autism Res} (Apr);3(2):68-77.
Fifteen adolescents and young adults with high-functioning autism spectrum disorders (ASD) and 18 age- and IQ-matched adults with typical development (TD) completed a serial reaction time task (SRT) to examine possible motor-linked implicit learning impairments in persons with ASD. Measures were taken to decrease the role of explicit learning in the SRT. Results showed that participants with ASD demonstrated intact motor-linked implicit learning. Furthermore, the motor-linked implicit learning appeared to take place at a similar rate across trials in the group with ASD compared to the group with TD. These results suggest that persons with ASD are successful in implicit learning of motor-linked behavior. The results of this study, coupled with past findings, suggest that people with ASD may be able to learn motor movements without conscious awareness, especially if the individual is older and is learning fine motor sequences.
17. Voracek M. {{Fetal androgens and autism}}. {Br J Psychiatry} (May);196(5):416; author reply 416-417.
18. Wan CY, Demaine K, Zipse L, Norton A, Schlaug G. {{From music making to speaking: Engaging the mirror neuron system in, autism}}. {Brain Res Bull} (Apr 27)
Individuals with autism show impairments in emotional tuning, social interactions and communication. These are functions that have been attributed to the putative human mirror neuron system (MNS), which contains neurons that respond to the actions of self and others. It has been proposed that a dysfunction of that system underlies some of the characteristics of autism. Here, we review behavioral and imaging studies that implicate the MNS (or a brain network with similar functions) in sensory-motor integration and speech representation, and review data supporting the hypothesis that MNS activity could be abnormal in autism. In addition, we propose that an intervention designed to engage brain regions that overlap with the MNS may have significant clinical potential. We argue that this engagement could be achieved through forms of music making. Music making with others (e.g., playing instruments or singing) is a multi-modal activity that has been shown to engage brain regions that largely overlap with the human MNS. Furthermore, many children with autism thoroughly enjoy participating in musical activities. Such activities may enhance their ability to focus and interact with others, thereby fostering the development of communication and social skills. Thus, interventions incorporating methods of music making may offer a promising approach for facilitating expressive language in otherwise nonverbal children with autism.
