1. Bastiaansen JA, Meffert H, Hein S, Huizinga P, Ketelaars C, Pijnenborg M, Bartels A, Minderaa R, Keysers C, de Bildt A. {{Diagnosing Autism Spectrum Disorders in Adults: the Use of Autism Diagnostic Observation Schedule (ADOS) Module 4}}. {J Autism Dev Disord};2010 (Dec 14)
Autism Diagnostic Observation Schedule (ADOS) module 4 was investigated in an independent sample of high-functioning adult males with an autism spectrum disorder (ASD) compared to three specific diagnostic groups: schizophrenia, psychopathy, and typical development. ADOS module 4 proves to be a reliable instrument with good predictive value. It can adequately discriminate ASD from psychopathy and typical development, but is less specific with respect to schizophrenia due to behavioral overlap between autistic and negative symptoms. However, these groups differ on some core items and explorative analyses indicate that a revision of the algorithm in line with Gotham et al. (J Autism Dev Disord 37: 613-627, 2007) could be beneficial for discriminating ASD from schizophrenia.
2. Bremer A, Giacobini M, Eriksson M, Gustavsson P, Nordin V, Fernell E, Gillberg C, Nordgren A, Uppstromer A, Anderlid BM, Nordenskjold M, Schoumans J. {{Copy number variation characteristics in subpopulations of patients with autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2010 (Dec 8)
Autism spectrum disorders (ASDs) are a heterogeneous group of disorders with a complex genetic etiology. We used high-resolution whole genome array-based comparative genomic hybridization (array-CGH) to screen 223 ASD patients for gene dose alterations associated with susceptibility for autism. Clinically significant copy number variations (CNVs) were identified in 18 individuals (8%), of which 9 cases (4%) had de novo aberrations. In addition, 20 individuals (9%) were shown to have CNVs of unclear clinical relevance. Among these, 13 cases carried rare but inherited CNVs that may increase the risk for developing ASDs, while parental samples were unavailable in the remaining seven cases. Classification of all patients into different phenotypic and inheritance pattern groups indicated the presence of different CNV patterns in different patient groups. Clinically relevant CNVs were more common in syndromic cases compared to non-syndromic cases. Rare inherited CNVs were present in a higher proportion of ASD cases having first- or second-degree relatives with an ASD-related neuropsychiatric phenotype in comparison with cases without reported heredity (P = 0.0096). We conclude that rare CNVs, encompassing potential candidate regions for ASDs, increase the susceptibility for the development of ASDs and related neuropsychiatric disorders giving us further insight into the complex genetics underlying ASDs. (c) 2010 Wiley-Liss, Inc.
3. Brown HK, Ouellette-Kuntz H, Hunter D, Kelley E, Cobigo V, Lam M. {{Beyond an Autism Diagnosis: Children’s Functional Independence and Parents’ Unmet Needs}}. {J Autism Dev Disord};2010 (Dec 14)
High demand has resulted in gaps in autism service provision. Our objective was to explore the association between children’s functioning and parents’ perceived unmet needs. We conducted a cross-sectional study of 97 families of school-aged children with an autism spectrum disorder. Log binomial regression was used to examine the relative risk for unmet need. Families of children with high functional independence had lower unmet need than families of children with moderate functional independence (RR = 0.81, 95% CI = 0.67-0.99). Those who experienced greater impact of the child’s disability had greater unmet need (RR = 1.22, 95% CI = 1.03-1.45). The child’s functioning and its impact on the family provide insight into unmet need which may inform service planning.
4. Charman T. {{Commentary: Glass half full or half empty? Testing social communication interventions for young children with autism – reflections on Landa, Holman, O’Neill, and Stuart (2011)}}. {J Child Psychol Psychiatry};2011 (Jan);52(1):22-23.
5. Darrou C, Pry R, Pernon E, Michelon C, Aussilloux C, Baghdadli A. {{Outcome of young children with autism: Does the amount of intervention influence developmental trajectories?}}. {Autism};2010 (Nov);14(6):663-677.
The study aims were to identify developmental trajectories of young children with autism and investigate their prognostic factors. The participants were 208 children, assessed first at the age of 5 years, followed longitudinally, and reassessed 3 years later. The children’s clinical characteristics and the interventions received were recorded. The results indicated two distinct outcome groups with more stability than change. When changes did occur, they pertained to symptom severity (which decreased) and speech level and adaptive behavior (which improved). A logistic regression analysis pointed out two main risk factors (symptom severity and speech level) and two main protection factors (communication skills and person-related cognition). Surprisingly, the amount of intervention (in terms of number of hours) was not related to outcome.
6. de Marchena A, Eigsti IM. {{Conversational gestures in autism spectrum disorders: Asynchrony but not decreased frequency}}. {Autism Res};2010 (Dec 9)
Conversational or « co-speech » gestures play an important role in communication, facilitating turntaking, providing visuospatial information, clarifying subtleties of emphasis, and other pragmatic cues. Consistent with other pragmatic language deficits, individuals with autism spectrum disorders (ASD) are said to produce fewer conversational gestures, as specified in many diagnostic measures. Surprisingly, while research shows fewer deictic gestures in young children with ASD, there is a little empirical evidence addressing other forms of gesture. The discrepancy between clinical and empirical observations may reflect impairments unrelated to frequency, such as gesture quality or integration with speech. Adolescents with high-functioning ASD (n=15), matched on age, gender, and IQ to 15 typically developing (TD) adolescents, completed a narrative task to assess the spontaneous production of speech and gesture. Naive observers rated the stories for communicative quality. Overall, the ASD group’s stories were rated as less clear and engaging. Although utterance and gesture rates were comparable, the ASD group’s gestures were less closely synchronized with the co-occurring speech, relative to control participants. This gesture-speech synchrony specifically impacted communicative quality across participants. Furthermore, while story ratings were associated with gesture count in TD adolescents, no such relationship was observed in adolescents with ASD, suggesting that gestures do not amplify communication in this population. Quality ratings were, however, correlated with ASD symptom severity scores, such that participants with fewer ASD symptoms were rated as telling higher quality stories. Implications of these findings are discussed in terms of communication and neuropsychological functioning in ASD.
7. Dichter GS, Felder JN, Green SR, Rittenberg AM, Sasson NJ, Bodfish JW. {{Reward circuitry function in autism spectrum disorders}}. {Soc Cogn Affect Neurosci};2010 (Dec 8)
Social interaction deficits and restricted repetitive behaviors and interests that characterize autism spectrum disorders (ASDs) may both reflect aberrant functioning of brain reward circuits. However, no neuroimaging study to date has investigated the integrity of reward circuits using an incentive delay paradigm in individuals with ASDs. In the present study, we used functional magnetic resonance imaging to assess blood-oxygen level-dependent activation during reward anticipation and outcomes in 15 participants with an ASD and 16 matched control participants. Brain activation was assessed during anticipation of and in response to monetary incentives and object image incentives previously shown to be visually salient for individuals with ASDs (e.g. trains, electronics). Participants with ASDs showed decreased nucleus accumbens activation during monetary anticipation and outcomes, but not during object anticipation or outcomes. Group x reward-type-interaction tests revealed robust interaction effects in bilateral nucleus accumbens during reward anticipation and in ventromedial prefrontal cortex during reward outcomes, indicating differential responses contingent on reward type in these regions. Results suggest that ASDs are characterized by reward-circuitry hypoactivation in response to monetary incentives but not in response to autism-relevant object images. The clinical implications of the double dissociation of reward type and temporal phase in reward circuitry function in ASD are discussed.
8. Gandal MJ, Edgar JC, Ehrlichman RS, Mehta M, Roberts TP, Siegel SJ. {{Validating gamma Oscillations and Delayed Auditory Responses as Translational Biomarkers of Autism}}. {Biol Psychiatry};2010 (Dec 15);68(12):1100-1106.
BACKGROUND: Difficulty modeling complex behavioral phenotypes in rodents (e.g., language) has hindered pathophysiological investigation and treatment development for autism spectrum disorders. Recent human neuroimaging studies, however, have identified functional biomarkers that can be more directly related to the abnormal neural dynamics of autism spectrum disorders. This study assessed the translational potential of auditory evoked-response endophenotypes of autism in parallel mouse and human studies of autism. METHODS: Whole-cortex magnetoencephalography was recorded in 17 typically developing and 25 autistic children during auditory pure-tone presentation. Superior temporal gyrus activity was analyzed in time and frequency domains. Auditory evoked potentials were recorded in mice prenatally exposed to valproic acid (VPA) and analyzed with analogous methods. RESULTS: The VPA-exposed mice demonstrated selective behavioral alterations related to autism, including reduced social interactions and ultrasonic vocalizations, increased repetitive self-grooming, and prepulse inhibition deficits. Autistic subjects and VPA-exposed mice showed a similar 10% latency delay in the N1/M100 evoked response and a reduction in gamma frequency (30-50 Hz) phase-locking factor. Electrophysiological measures were associated with mouse behavioral deficits. In mice, gamma phase-locking factor was correlated with expression of the autism risk gene neuroligin-3 and neural deficits were modulated by the mGluR5-receptor antagonist MPEP. CONCLUSIONS: Results demonstrate a novel preclinical approach toward mechanistic understanding and treatment development for autism.
9. Goldberg MC, Spinelli S, Joel S, Pekar JJ, Denckla MB, Mostofsky SH. {{Children with High Functioning Autism show increased prefrontal and temporal cortex activity during error monitoring}}. {Dev Cogn Neurosci};2011 (Jan 1);1(1):47-56.
Evidence exists for deficits in error monitoring in autism. These deficits may be particularly important because they may contribute to excessive perseveration and repetitive behavior in autism. We examined the neural correlates of error monitoring using fMRI in 8-12-year-old children with high-functioning autism (HFA, n=11) and typically developing children (TD, n=15) during performance of a Go/No-Go task by comparing the neural correlates of commission errors versus correct response inhibition trials. Compared to TD children, children with HFA showed increased BOLD fMRI signal in the anterior medial prefrontal cortex (amPFC) and the left superior temporal gyrus (STempG) during commission error (versus correct inhibition) trials. A follow-up region-of-interest analysis also showed increased BOLD signal in the right insula in HFA compared to TD controls. Our findings of increased amPFC and STempG activity in HFA, together with the increased activity in the insula, suggest a greater attention towards the internally-driven emotional state associated with making an error in children with HFA. Since error monitoring occurs across different cognitive tasks throughout daily life, an increased emotional reaction to errors may have important consequences for early learning processes.
10. Grether JK, Croen LA, Anderson MC, Nelson KB, Yolken RH. {{Neonatally measured immunoglobulins and risk of autism}}. {Autism Res};2010 (Dec 9)
Previous studies indicate that prenatal exposure to infections is a possible pathway through which autism spectrum disorders (ASD) could be initiated. We investigated whether immunoglobulin levels in archived specimens obtained from newborns subsequently diagnosed with ASD are different from levels in newborn specimens from controls. Children with ASD born in six California counties in 1994 were ascertained through records of the California Department of Developmental Services (DDS) and Kaiser Permanente; controls were randomly selected using birth certificates. Archived newborn blood specimens were obtained from the California Genetic Disease Screening Program (GDSP) for N = 213 cases and N = 265 controls and assayed to determine levels of total IgG, antigen-specific IgG to selected common pathogens, total IgM, total IgA, and C-reactive protein (CRP). We did not find measurable levels of total IgM or IgA in any neonate and measurable CRP was present in only a few. No antigen-specific IgG antibodies were elevated in cases compared to controls and total IgG levels were lower. In adjusted models, a 10-unit increase in total IgG yielded an OR = 0.72 (95% CI 0.56, 0.91); a significantly decreasing trend in risk of ASD was observed across increasing exposure quartiles of total IgG (P = 0.01). The finding of lower IgG in cases may indicate maternal immune dysfunction during gestation and/or impaired transplacental transfer of immunoglobulins. Further investigation of IgG levels in newborns and the mechanisms by which they might be associated with ASD are warranted.
11. Harony H, Wagner S. {{The Contribution of Oxytocin and Vasopressin to Mammalian Social Behavior: Potential Role in Autism Spectrum Disorder}}. {Neurosignals};2010 (Dec 11)
Oxytocin (OT) and arginine-vasopressin (AVP) are 2 peptides that are produced in the brain and released via the pituitary gland to the peripheral blood, where they have diverse physiological functions. In the last 2 decades it has become clear that these peptides also play a central role in the modulation of mammalian social behavior by their actions within the brain. Several lines of evidence suggest their involvement in autism spectrum disorder (ASD), which is known to be associated with impaired social cognition and behavior. Recent clinical trials using OT administration to autistic patients have reported promising results. Here, we aim to describe the main data that suggest a connection between these peptides and ASD. Following a short illustration of several major topics in ASD biology we will (a) briefly describe the oxytocinergic and vasopressinergic systems in the brain, (b) discuss a few compelling cases manifesting the involvement of OT and AVP in mammalian social behavior, (c) describe data supporting the role of these peptides in human social cognition and behavior, and (d) discuss the possibility of the involvement of OT and AVP in ASD etiology, as well as the prospect of using these peptides as a treatment for ASD patients.
12. Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK. {{Rett syndrome: Revised diagnostic criteria and nomenclature}}. {Ann Neurol};2010 (Dec 8)
OBJECTIVE: Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. METHOD: RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. RESULTS: The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. INTERPRETATION: These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. Ann Neurol 2010.
13. Kistner-Griffin E, Brune CW, Davis LK, Sutcliffe JS, Cox NJ, Cook EH, Jr. {{Parent-of-origin effects of the serotonin transporter gene associated with autism}}. {Am J Med Genet B Neuropsychiatr Genet};2010 (Dec 8)
A promoter-linked insertion/deletion polymorphism of the serotonin transporter gene (SLC6A4) has been implicated in autism spectrum disorders (ASDs) in numerous family based association studies. However, the results of these investigations have been inconsistent in that both the long and short alleles have been shown to be over-transmitted to affected offspring. In order to further elucidate the relationship between the 5-HTTLPR variant and autism risk, we undertook a thorough study of parent-of-origin effects, maternal genotype effects, and offspring genotype effects in a sample of affected offspring from the Autism Genetic Resource Exchange (AGRE). Both the overall autism phenotype and measures of autism behaviors from the Autism Diagnostic Interview-Revised [Lord et al. (1994); J Autism Dev Disord 24(5): 659-685] were considered. We found evidence of over-transmission (risk allele short, P = 0.012), maternal effects (risk allele long, P = 0.035), and parent-of-origin effects (risk allele short from mother, P = 0.018) of the 5-HTTLPR variant in the AGRE sample. Population- and gender-specific effects were also explored as associations may be heterogeneous across populations and sexes. Parent-of-origin effects of the variant were associated with maternally inherited copies of the short allele that resulted in more impaired overall level of language (P = 0.04). Our study was conducted to further investigate the 5-HTTLPR risk variants by identifying allelic associations that may be population-specific, phenotype-specific, or conferred by maternal or parent-of-origin effects. In light of conflicting observations from previous studies, these are just a few of the possible explanations that deserve attention. (c) 2010 Wiley-Liss, Inc.
14. Lai MC, Lombardo MV, Chakrabarti B, Sadek SA, Pasco G, Wheelwright SJ, Bullmore ET, Baron-Cohen S, Suckling J. {{A shift to randomness of brain oscillations in people with autism}}. {Biol Psychiatry};2010 (Dec 15);68(12):1092-1099.
BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) enables investigation of the intrinsic functional organization of the brain. Fractal parameters such as the Hurst exponent, H, describe the complexity of endogenous low-frequency fMRI time series on a continuum from random (H = .5) to ordered (H = 1). Shifts in fractal scaling of physiological time series have been associated with neurological and cardiac conditions. METHODS: Resting-state fMRI time series were recorded in 30 male adults with an autism spectrum condition (ASC) and 33 age- and IQ-matched male volunteers. The Hurst exponent was estimated in the wavelet domain and between-group differences were investigated at global and voxel level and in regions known to be involved in autism. RESULTS: Complex fractal scaling of fMRI time series was found in both groups but globally there was a significant shift to randomness in the ASC (mean H = .758, SD = .045) compared with neurotypical volunteers (mean H = .788, SD = .047). Between-group differences in H, which was always reduced in the ASC group, were seen in most regions previously reported to be involved in autism, including cortical midline structures, medial temporal structures, lateral temporal and parietal structures, insula, amygdala, basal ganglia, thalamus, and inferior frontal gyrus. Severity of autistic symptoms was negatively correlated with H in retrosplenial and right anterior insular cortex. CONCLUSIONS: Autism is associated with a small but significant shift to randomness of endogenous brain oscillations. Complexity measures may provide physiological indicators for autism as they have done for other medical conditions.
15. Lu AT, Cantor RM. {{Allowing for sex differences increases power in a GWAS of multiplex Autism families}}. {Mol Psychiatry};2010 (Dec 14)
Current genomewide association studies account for only a small fraction of the estimated heritabilities of genetically complex neuropsychiatric disorders, indicating they are likely to result from the small effects of numerous predisposing variants, many of which have gone undetected. The statistical power to detect associations of common variants with small effects is increased by conducting joint association tests of a single nucleotide polymorphism (SNP), an additional risk factor (F), and their interaction. F can represent an environmental exposure, another genotype or any source of genetic heterogeneity. In case and control studies, logistic regression makes joint tests straightforward. This analytic method cannot be employed directly when SNP transmission tests are used to detect associations in parent/affected child trios and multiplex families. However, the method can be implemented using the case/pseudocontrol approach. We applied this approach to analyze data from a genomewide association study of multiplex families ascertained for Autism Spectrum Disorder, where sex was used to define the F. Joint analyses revealed two associations exceeding genomewide significance. One novel gene, Ryandine Receptor 2, implicated in calcium channel defects, was identified with a joint P-value of 3.9E-11. Calcium channel defects have been connected to Autism spectrum disorder (ASD) by Timothy Syndrome, which is Mendelian, and a previous targeted sex-specific association analysis of idiopathic Autism. A second gene, uridine phosphorylase 2, with a joint P-value of 2.3E-9, has been previously linked and associated with Autism in independent samples. These findings highlight two Autism candidate genes for follow-up studies.Molecular Psychiatry advance online publication, 14 December 2010; doi:10.1038/mp.2010.127.
16. Martirosian G, Ekiel A, Aptekorz M, Wiechula B, Kazek B, Jankowska-Steifer E, Jozwiak J, Moskalewski S. {{Fecal lactoferrin and Clostridium spp. in stools of autistic children}}. {Anaerobe};2010 (Dec 15)
Stools from autistic and healthy children were studied for fecal lactoferrin, Clostridium difficile toxins, Clostridium perfringens enterotoxin and cultured for Clostridium spp. Elevated level of FLA was demonstrated in 24.4% stools, all from boys (31.25%). No toxins were detected. Clostridium spp. were isolated with similar frequency from all samples. C. perfringens were isolated significantly often from the autistic stools, intermediate sensitive strains to penicillin 19%, to clindamycin 11.3%, and to metronidazole 7.5 % were detected. Further studies on fecal microflora and inflammatory mediators, with larger groups of patients, are required in order to explain their role in neurological deficits.
17. Matson JL, Kozlowski AM, Worley JA, Shoemaker ME, Sipes M, Horovitz M. {{What is the evidence for environmental causes of challenging behaviors in persons with intellectual disabilities and autism spectrum disorders?}}. {Res Dev Disabil};2010 (Dec 6)
An extensive literature on the causes of challenging behaviors has been developed, primarily in the applied behavior analysis literature. One hundred and seventy-three empirical studies were reviewed where functional assessment serves as the primary method of identifying these causes. Most of the studies were able to identify a clear function or functions. Most commonly established causes were attention, the efforts to acquire tangibles, negative reinforcement in the form of escape from tasks or environments, and sensory stimulation, also described as an alone condition. Examples are provided regarding how these conditions are investigated across studies. Biological and cognitive causes have also been demonstrated. However, to date the empirical literature is limited with the bulk of studies being correlational. Considerably more research is needed, but some causes and methods to identify them are beginning to emerge.
18. Mengotti P, D’Agostini S, Terlevic R, De Colle C, Biasizzo E, Londero D, Ferro A, Rambaldelli G, Balestrieri M, Zanini S, Fabbro F, Molteni M, Brambilla P. {{Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study}}. {Brain Res Bull};2010 (Dec 9)
BACKGROUND: A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism. METHODS: Twenty children with autism (mean age=7+/-2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age=7.68+/-2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardised at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b=0) and were then automatically transferred to the corresponding maps to obtain the ADC values. RESULTS: Compared to normal children, individuals with autism had significantly (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development. CONCLUSIONS: These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits.
19. Rondeau E, Klein LS, Masse A, Bodeau N, Cohen D, Guile JM. {{Is Pervasive Developmental Disorder Not Otherwise Specified Less Stable Than Autistic Disorder? A Meta-Analysis}}. {J Autism Dev Disord};2010 (Dec 14)
We reviewed the stability of the diagnosis of pervasive developmental disorder not otherwise specified (PDD-NOS). A Medline search found eight studies reiterating a diagnostic assessment for PDD-NOS. The pooled group included 322 autistic disorder (AD) and 122 PDD-NOS cases. We used percentage of individuals with same diagnose at Times 1 and 2 as response criterion. The pooled Relative Risk was 1.95 (p < 0.001) showing that AD diagnostic stability was higher than PDD-NOS. When diagnosed before 36 months PDD-NOS bore a 3-year stability rate of 35%. Examining the developmental trajectories showed that PDD-NOS corresponded to a group of heterogeneous pathological conditions including prodromic forms of later AD, remitted or less severe forms of AD, and developmental delays in interaction and communication.
20. Smith T, Eikeseth S. {{O. Ivar Lovaas: Pioneer of Applied Behavior Analysis and Intervention for Children with Autism}}. {J Autism Dev Disord};2010 (Dec 14)
O. Ivar Lovaas (1927-2010) devoted nearly half a century to ground-breaking research and practice aimed at improving the lives of children with autism and their families. In the 1960s, he pioneered applied behavior analytic (ABA) interventions to decrease severe challenging behaviors and establish communicative language. Later, he sought to improve outcomes by emphasizing early intervention for preschoolers with autism, provided in family homes with active parental participation. His studies indicated that many children who received early intensive ABA made dramatic gains in development. Lovaas also disseminated ABA widely through intervention manuals, educational films, and public speaking. Moreover, as an enthusiastic teacher and devoted mentor, he inspired many students and colleagues to enter the field of ABA and autism intervention.
21. Spengler S, Bird G, Brass M. {{Hyperimitation of actions is related to reduced understanding of others’ minds in autism spectrum conditions}}. {Biol Psychiatry};2010 (Dec 15);68(12):1148-1155.
BACKGROUND: Anecdotal evidence has noted that individuals with autism spectrum conditions (ASC) frequently exhibit heightened spontaneous imitative behavior, with symptoms of echolalia and echopraxia. This is contrasted by empiric reports that ASC results in decreased imitation and an underlying deficit in the mirror system, leading to impaired social understanding. Thus, it remains unclear whether automatic imitation is enhanced in ASC and how this is related to poorer social abilities. METHODS: This study investigated spontaneous imitation in 18 high-functioning adults with ASC and 18 age- and IQ-matched control participants during a simple imitation inhibition task. Mentalizing was experimentally assessed in the same participants using both behavioral and functional magnetic resonance imaging measures, as was social interaction using an observational measure. RESULTS: Individuals with ASC showed increased imitation of hand actions compared with control participants and this was associated with reduced mentalizing and poorer reciprocal social interaction abilities. In the functional magnetic resonance imaging mentalizing paradigm, ASC participants with increased imitation scores showed less brain activation in areas often found to be active in mental state attribution, namely the medial prefrontal cortex and temporoparietal junction. CONCLUSIONS: The results confirm the presence of hyperimitation in ASC, which is accompanied by reduced social cognition, suggesting that a general imitation impairment and a global mirror system deficit are absent. These findings offer an explanation for echopractic features based on theories of atypical functioning of top-down modulation processes in autism.
22. Stevenson JL, Kellett KA. {{Can magnetic resonance imaging aid diagnosis of the autism spectrum?}}. {J Neurosci};2010 (Dec 15);30(50):16763-16765.
23. Teixeira MC, Mecca TP, Velloso RD, Bravo RB, Ribeiro SH, Mercadante MT, Paula CS. {{[Brazilian scientific literature about autism spectrum disorders.]}}. {Rev Assoc Med Bras};2010;56(5):607-614.
OBJECTIVE: This study is a systematic review aiming to conduct a general analysis of the scientific production covering publications of Brazilian authors about ASD in the period from 2002 to 2009. METHODS: The bibliographic search was conducted in the following scientific databases: PUBMED, SciELO, LILACS and portal CAPES, by using keywords such as autism and pervasive developmental disorders. RESULTS: A total of 93 papers were identified mainly produced by authors from tSoutheast Brazil and from public universities. Approximately one third of the papers was published in journals with a level of impact factor that ranged from 0.441 to 3.211; most of them were based on small sample sizes. Identified were 140 dissertations/theses; 82.1% were masters theses. The major research topic was related to intervention programs addressing ASD. CONCLUSION: This review shows that Brazilian researchers are interested in the ASD theme, however, a large part of this scientific production is concentrated in dissertation/masters theses and the minority of papers was published in journals with a high impact factor. Results of this systematic review suggest the need for studies with larger sample sizes which would produce greater impact and visibility in the Brazilian scientific production in the field of the ASD.
24. Vlamings PH, Jonkman LM, van Daalen E, van der Gaag RJ, Kemner C. {{Basic abnormalities in visual processing affect face processing at an early age in autism spectrum disorder}}. {Biol Psychiatry};2010 (Dec 15);68(12):1107-1113.
BACKGROUND: A detailed visual processing style has been noted in autism spectrum disorder (ASD); this contributes to problems in face processing and has been directly related to abnormal processing of spatial frequencies (SFs). Little is known about the early development of face processing in ASD and the relation with abnormal SF processing. We investigated whether young ASD children show abnormalities in low spatial frequency (LSF, global) and high spatial frequency (HSF, detailed) processing and explored whether these are crucially involved in the early development of face processing. METHODS: Three- to 4-year-old children with ASD (n = 22) were compared with developmentally delayed children without ASD (n = 17). Spatial frequency processing was studied by recording visual evoked potentials from visual brain areas while children passively viewed gratings (HSF/LSF). In addition, children watched face stimuli with different expressions, filtered to include only HSF or LSF. RESULTS: Enhanced activity in visual brain areas was found in response to HSF versus LSF information in children with ASD, in contrast to control subjects. Furthermore, facial-expression processing was also primarily driven by detail in ASD. CONCLUSIONS: Enhanced visual processing of detailed (HSF) information is present early in ASD and occurs for neutral (gratings), as well as for socially relevant stimuli (facial expressions). These data indicate that there is a general abnormality in visual SF processing in early ASD and are in agreement with suggestions that a fast LSF subcortical face processing route might be affected in ASD. This could suggest that abnormal visual processing is causative in the development of social problems in ASD.
25. Yamasaki S, Yamasue H, Abe O, Suga M, Yamada H, Inoue H, Kuwabara H, Kawakubo Y, Yahata N, Aoki S, Kano Y, Kato N, Kasai K. {{Reduced gray matter volume of pars opercularis is associated with impaired social communication in high-functioning autism spectrum disorders}}. {Biol Psychiatry};2010 (Dec 15);68(12):1141-1147.
BACKGROUND: Recent literature suggests that the inferior frontal gyrus, especially its posterior portion, has an important role in imitation and social reciprocity and in the pathophysiology of their disturbance in autism spectrum disorders (ASD). However, the structural abnormality of this region has not fully been clarified in subjects with ASD. METHODS: Here we obtained magnetic resonance images from 13 right-handed men with high-functioning ASD (Asperger disorder [n = 10] or autism [n = 3]) and from 11 age-, parental socioeconomic background-, and intelligence quotient-matched right-handed typical men. A reliable manual tracing methodology was employed to measure the gray matter volume of the pars opercularis, corresponding to Brodmann area 44, and the pars triangularis, corresponding to Brodmann area 45. RESULTS: A significant gray matter volume reduction of both the pars opercularis and triangularis was found bilaterally in the subjects with ASD compared with the typical control subjects. The effect size seemed to be larger for pars opercularis (1.25) than for pars triangularis (.90). The reduced volume of right as well as total pars opercularis showed a significant association with the increased severity of social communication problems in the ASD group. CONCLUSIONS: The current findings support an important role of pars opercularis, a center of the mirror neuron system, in the pathophysiology of ASD.
26. Yan G, Liang Y, Wang Y, Huang W, Zou X, Zhong N. {{[Copy number variation analysis of a Chinese Han family with autism spectrum disorder.]}}. {Zhonghua Yi Xue Yi Chuan Xue Za Zhi};2010 (Dec 10);27(6):654-658.
OBJECTIVE: To study the copy number variation (CNV) in a Chinese Han autistic spectrum disorder (ASD) pedigree. METHODS: The pedigree involved six siblings, and three of them were autistic. B lymphocytes of the pedigree were immortalized with EBV and used as studying materials. Karyotyping and Affymatrix 500k SNP chip assay were performed to assess the genetic defects among the members of the pedigree. RESULTS: Karyotyping indicated that the chromosomes were normal. However, the 15q11 locus was located as de novo CNV region in all autistic siblings of the pedigree. In this locus, the fragment in 19827281-19998230 illustrated « loss » of CNV, while other three fragments with 37 kb, 1316 kb and 37 kb indicated « gain » of CNV. CONCLUSION: In this study, olfactory genes OR11K1P, OR4Q1P, OR4H6P, OR4M2, etc. in the sites with loss and gain of CNV may provide a new clue for genetic research of autism spectrum disorder.
