1. Absoud M, Parr JR, Salt A, Dale N. {{Developing a schedule to identify social communication difficulties and autism spectrum disorder in young children with visual impairment}}. {Dev Med Child Neurol};2011 (Mar);53(3):285-288.
Available observational tools used in the identification of social communication difficulties and diagnosis of autism spectrum disorder (ASD) rely partly on visual behaviours and therefore may not be valid in children with visual impairment. A pilot observational instrument, the Visual Impairment and Social Communication Schedule (VISS), was developed to aid in identifying social communication difficulties and ASD in young children with visual impairment affected by congenital disorders of the peripheral visual system (disorders of the globe, retina, and anterior optic nerve). The VISS was administered to 23 consecutive children (age range 1y 9mo-6y 11mo, mean 4y 1mo [SD 1.6]; 12 males, 11 females) with visual impairment (nine with severe and 14 with profound visual impairment). Item analysis was carried out by fit of the items to the Rasch model. Validity of the VISS was explored by comparison with the Childhood Autism Rating Scale (CARS) score, and the clinical ASD diagnosis (n=9). Correlation between the VISS and CARS total scores was highly significant (Spearman’s rho=-0.89; p=0.01). Below threshold rating on the VISS (score of 35) showed good agreement with the clinical ASD diagnosis (sensitivity 89%, specificity 100%). This preliminary study shows the VISS to be a promising schedule to aid the identification of ASD in young children with visual impairment.
2. Adamsen D, Meili D, Blau N, Thony B, Ramaekers V. {{Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants}}. {Mol Genet Metab};2011 (Mar);102(3):368-373.
The known Gly56Ala mutation in the serotonin transporter SERT (or 5-HTT), encoded by the SLC6A4 gene, causes increased serotonin reuptake and has been associated with autism and rigid-compulsive behavior. We report a patient with macrocephaly from birth, followed by hypotonia, developmental delay, ataxia and a diagnosis of atypical autism (PDD-NOS) in retrospect at the age of 4(1/2)years. Low levels of the serotonin end-metabolite 5-hydroxyindolacetic acid (5HIAA) in CSF were detected, and SLC6A4 gene analysis revealed the heterozygous Gly56Ala alteration and the homozygous 5-HTTLPR L/L promoter variant. These changes are reported to be responsible for elevated SERT activity and expression, suggesting that these alterations were responsible in our patient for low serotonin turnover in the central nervous system (CNS). Daily treatment with 5-hydroxytryptophan (and carbidopa) led to clinical improvement and normalization of 5HIAA, implying that brain serotonin turnover normalized. We speculate that the mutated 56Ala SERT transporter with elevated expression and basal activity for serotonin re-uptake is accompanied with serotonin accumulation within pre-synaptic axons and their vesicles in the CNS, resulting in a steady-state of lowered serotonin turnover and degradation by monoamine-oxidase (MAO) enzymes in pre-synaptic or neighboring cells.
3. Addington AM, Gauthier J, Piton A, Hamdan FF, Raymond A, Gogtay N, Miller R, Tossell J, Bakalar J, Germain G, Gochman P, Long R, Rapoport JL, Rouleau GA. {{A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders}}. {Mol Psychiatry};2011 (Mar);16(3):238-239.
4. Ames CS, White SJ. {{Brief report: are ADHD traits dissociable from the autistic profile? Links between cognition and behaviour}}. {J Autism Dev Disord};2011 (Mar);41(3):357-363.
Reports of co-morbid symptoms of ADHD in children with ASD have increased. This research sought to identify ADHD-related behaviours in a sample of children with ASD, and their relationship with the ASD triad of impairments and related cognitive impairments. Children with ASD (n = 55) completed a comprehensive cognitive assessment whilst a semi-structured parental interview (3Di) provided information on ASD and ADHD symptoms. Co-morbid presentation of ADHD traits in these participants was associated with reports of more ASD related behaviours. Inhibitory control performance was directly related only to the ADHD symptom of impulsive behaviour. In contrast, while there was a relationship between social difficulties associated with ASD and theory of mind ability, there was no such relationship with behaviours relating to ADHD.
5. 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};2011 (Mar);156(2):115-124.
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.
6. Chang SC, Pauls DL, Lange C, Sasanfar R, Santangelo SL. {{Common genetic variation in the GAD1 gene and the entire family of DLX homeobox genes and autism spectrum disorders}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Mar);156(2):233-239.
Biological and positional evidence supports the involvement of the GAD1 and distal-less homeobox genes (DLXs) in the etiology of autism. We investigated 42 single nucleotide polymorphisms in these genes as risk factors for autism spectrum disorders (ASD) in a large family-based association study of 715 nuclear families. No single marker showed significant association after correction for multiple testing. A rare haplotype in the DLX1 promoter was associated with ASD (P-value = 0.001). Given the importance of rare variants to the etiology of autism revealed in recent studies, the observed rare haplotype may be relevant to future investigations. Our observations, when taken together with previous findings, suggest that common genetic variation in the GAD1 and DLX genes is unlikely to play a critical role in ASD susceptibility. (c) 2010 Wiley-Liss, Inc.
7. Charman T, Pickles A, Simonoff E, Chandler S, Loucas T, Baird G. {{IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP)}}. {Psychol Med};2011 (Mar);41(3):619-627.
BACKGROUND: Autism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of ‘peaks’ and ‘troughs’ at the subtest level. However, there are few data from epidemiological studies. METHOD: Comprehensive clinical assessments were conducted with 156 children aged 10-14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population. RESULTS: Of the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbal versus performance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no ‘peak’ in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ. CONCLUSIONS: In this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.
8. Crepel A, Steyaert J, De la Marche W, De Wolf V, Fryns JP, Noens I, Devriendt K, Peeters H. {{Narrowing the critical deletion region for autism spectrum disorders on 16p11.2}}. {Am J Med Genet B Neuropsychiatr Genet};2011 (Mar);156(2):243-245.
9. de Bildt A, Oosterling IJ, van Lang ND, Sytema S, Minderaa RB, van Engeland H, Roos S, Buitelaar JK, van der Gaag RJ, de Jonge MV. {{Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample}}. {J Autism Dev Disord};2011 (Mar);41(3):311-319.
The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693-705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning.
10. Drahota A, Wood JJ, Sze KM, Van Dyke M. {{Effects of cognitive behavioral therapy on daily living skills in children with high-functioning autism and concurrent anxiety disorders}}. {J Autism Dev Disord};2011 (Mar);41(3):257-265.
CBT is a promising treatment for children with autism spectrum disorders (ASD) and focuses, in part, on children’s independence and self-help skills. In a trial of CBT for anxiety in ASD (Wood et al. in J Child Psychol Psychiatry 50:224-234, 2009), children’s daily living skills and related parental intrusiveness were assessed. Forty children with ASD (7-11 years) and their primary caregiver were randomly assigned to an immediate treatment (IT; n = 17) or 3-month waitlist (WL; n = 23) condition. In comparison to WL, IT parents reported increases in children’s total and personal daily living skills, and reduced involvement in their children’s private daily routines. Reductions correlated with reduced anxiety severity. These results provide preliminary evidence that CBT may yield increased independence and daily living skills among children with ASD.
11. Enticott PG, Kennedy HA, Zangen A, Fitzgerald PB. {{Deep repetitive transcranial magnetic stimulation associated with improved social functioning in a young woman with an autism spectrum disorder}}. {J ECT};2011 (Mar);27(1):41-43.
OBJECTIVES: : There are currently no biomedical treatments targeting the core symptoms of autism spectrum disorders (ASDs). Considering evidence for cortical dysfunction in ASD, repetitive transcranial magnetic stimulation (rTMS) has been discussed as a potential therapeutic technique. METHODS: : We describe the application of a new type of rTMS, deep rTMS, to the bilateral medial prefrontal cortex in a young woman with a high-functioning ASD. High-frequency rTMS was applied for 15 minutes each consecutive weekday for an 11-day period (9 treatments in total). Self-reported assessments were conducted before the first rTMS session, immediately after the last rTMS session, and 1-month after the last rTMS session. RESULTS: : Self-reported assessments revealed a number of improvements after deep rTMS. These were primarily in the domain of social relating and interpersonal understanding and were corroborated by family members. CONCLUSIONS: : Deep rTMS in ASD may serve to remediate aspects of cortical dysfunction (as standard rTMS seems to do in depression and schizophrenia) and provides a potential new avenue for the development of a biomedical treatment of impaired social relating in ASD.
12. Farmer CA, Aman MG. {{Aripiprazole for the treatment of irritability associated with autism}}. {Expert Opin Pharmacother};2011 (Mar);12(4):635-640.
Introduction: Irritability (including tantrums, aggression and moodiness) is often associated with autistic disorder. Children with autism are frequently prescribed atypical antipsychotic medications for these behaviors. Although multiple agents have been found to be effective, the safety and tolerability of each antipsychotic may be the determining factor in its selection. Areas covered: The pharmacokinetics, pharmacodynamics, safety and efficacy data on aripiprazole for the treatment of irritability associated with autism are discussed. Knowledge of the mechanism of action, advantages and disadvantages relative to other atypical antipsychotics, and an appreciation of the efficacy of aripiprazole when used to treat irritability in autism is also explored in this paper. Expert opinion: Aripiprazole may have a more favorable side-effect profile than another commonly prescribed medication, risperidone, because of its unique mechanism of action. It seems to be effective in treating irritability associated with autism, but more research is needed.
13. Goines P, Haapanen L, Boyce R, Duncanson P, Braunschweig D, Delwiche L, Hansen R, Hertz-Picciotto I, Ashwood P, Van de Water J. {{Autoantibodies to cerebellum in children with autism associate with behavior}}. {Brain Behav Immun};2011 (Mar);25(3):514-523.
Autism is a heterogeneous disorder with a poorly understood biological basis. Some children with autism harbor plasma autoantibodies that target brain proteins. Similarly, some mothers of children with autism produce antibodies specific to autism that target pairs of fetal brain proteins at 37/73 and 39/73kDa. We explored the relationship between the presence of brain-specific autoantibodies and several behavioral characteristics of autism in 277 children with an autism spectrum disorder and 189 typically developing age-matched controls. Further, we used maternal autoantibody data to investigate potential familial relationships for the production of brain-directed autoantibodies. We demonstrated by Western blot that autoantibodies specific for a 45kDa cerebellar protein in children were associated with a diagnosis of autism (p=0.017) while autoantibodies directed towards a 62kDa protein were associated with the broader diagnosis of autism spectrum disorder (ASD) (p=0.043). Children with such autoantibodies had lower adaptive (p=0.0008) and cognitive function (p=0.005), as well as increased aberrant behaviors (p<0.05) compared to children without these antibodies. No correlation was noted for those mothers with the most specific pattern of anti-fetal brain autoantibodies and children with the autoantibodies to either the 45 or 62kDa bands. Collectively, these data suggest that antibodies towards brain proteins in children are associated with lower adaptive and cognitive function as well as core behaviors associated with autism. It is unclear whether these antibodies have direct pathologic significance, or if they are merely a response to previous injury. Future studies are needed to determine the identities of the protein targets and explore their significance in autism.
14. Good P. {{Does Fever relieve autistic behavior by improving brain blood flow?}}. {Neuropsychol Rev};2011 (Mar);21(1):66-67.
15. Jarocka-Cyrta E, Wasilewska J, Kaczmarski MG. {{Brief report: eosinophilic esophagitis as a cause of feeding problems in autistic boy. The first reported case}}. {J Autism Dev Disord};2011 (Mar);41(3):372-374.
Unrecognized gastrointestinal disorders may contribute to the behavioral problems in non-verbal patients, but they are often overlooked since the clinical symptoms are nonspecific. Eosinophilic esophagitis (EE) is a chronic inflammatory disorder manifesting itself predominantly in reflux-type symptoms that do not respond to standard anti-reflux pharmacotherapy. Here we report the first case of EE in an autistic patient with feeding difficulties caused by exacerbated EE symptoms.
16. Jones CR, Pickles A, Falcaro M, Marsden AJ, Happe F, Scott SK, Sauter D, Tregay J, Phillips RJ, Baird G, Simonoff E, Charman T. {{A multimodal approach to emotion recognition ability in autism spectrum disorders}}. {J Child Psychol Psychiatry};2011 (Mar);52(3):275-285.
Background: Autism spectrum disorders (ASD) are characterised by social and communication difficulties in day-to-day life, including problems in recognising emotions. However, experimental investigations of emotion recognition ability in ASD have been equivocal, hampered by small sample sizes, narrow IQ range and over-focus on the visual modality. Methods: We tested 99 adolescents (mean age 15;6 years, mean IQ 85) with an ASD and 57 adolescents without an ASD (mean age 15;6 years, mean IQ 88) on a facial emotion recognition task and two vocal emotion recognition tasks (one verbal; one non-verbal). Recognition of happiness, sadness, fear, anger, surprise and disgust were tested. Using structural equation modelling, we conceptualised emotion recognition ability as a multimodal construct, measured by the three tasks. We examined how the mean levels of recognition of the six emotions differed by group (ASD vs. non-ASD) and IQ (>/= 80 vs. < 80). Results: We found no evidence of a fundamental emotion recognition deficit in the ASD group and analysis of error patterns suggested that the ASD group were vulnerable to the same pattern of confusions between emotions as the non-ASD group. However, recognition ability was significantly impaired in the ASD group for surprise. IQ had a strong and significant effect on performance for the recognition of all six emotions, with higher IQ adolescents outperforming lower IQ adolescents. Conclusions: The findings do not suggest a fundamental difficulty with the recognition of basic emotions in adolescents with ASD.
17. Kinsbourne M. {{The Immune System’s Moderating Response to Inflammation Relieves Autistic Behavior: Response to Peter Good}}. {Neuropsychol Rev};2011 (Mar);21(1):68-69.
18. Kirby RS, Wingate MS, Van Naarden Braun K, Doernberg NS, Arneson CL, Benedict RE, Mulvihill B, Durkin MS, Fitzgerald RT, Maenner MJ, Patz JA, Yeargin-Allsopp M. {{Prevalence and functioning of children with cerebral palsy in four areas of the United States in 2006: A report from the Autism and Developmental Disabilities Monitoring Network}}. {Res Dev Disabil};2011 (Mar-Apr);32(2):462-469.
AIM: To estimate the prevalence of cerebral palsy (CP) and the frequency of co-occurring developmental disabilities (DDs), gross motor function (GMF), and walking ability using the largest surveillance DD database in the US. METHODS: We conducted population-based surveillance of 8-year-old children in 2006 (N=142,338), in areas of Alabama, Georgia, Wisconsin, and Missouri. This multi-site collaboration involved retrospective record review at multiple sources. We reported CP subtype, co-occurring DDs, Gross Motor Function Classification System (GMFCS) level, and walking ability as well as CP period prevalence by race/ethnicity and sex. RESULTS: CP prevalence was 3.3 (95% confidence interval [CI]: 3.1-3.7) per 1000 and varied by site, ranging from 2.9 (Wisconsin) to 3.8 (Georgia) per 1000, 8-year olds (p<0.02). Approximately 81% had spastic CP. Among children with CP, 8% had an autism spectrum disorder and 35% had epilepsy. Using the GMFCS, 38.1% functioned at the highest level (I), with 17.1% at the lowest level (V). Fifty-six percent were able to walk independently and 33% had limited or no walking ability. INTERPRETATION: Surveillance data are enhanced when factors such as functioning and co-occurring conditions known to affect clinical service needs, quality of life, and health care are also considered.
19. 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};2011 (Mar);156(2):139-144.
20. Klintwall L, Holm A, Eriksson M, Carlsson LH, Olsson MB, Hedvall A, Gillberg C, Fernell E. {{Sensory abnormalities in autism A brief report}}. {Res Dev Disabil};2011 (Mar-Apr);32(2):795-800.
Sensory abnormalities were assessed in a population-based group of 208 20-54-month-old children, diagnosed with autism spectrum disorder (ASD) and referred to a specialized habilitation centre for early intervention. The children were subgrouped based upon degree of autistic symptoms and cognitive level by a research team at the centre. Parents were interviewed systematically about any abnormal sensory reactions in the child. In the whole group, pain and hearing were the most commonly affected modalities. Children in the most typical autism subgroup (nuclear autism with no learning disability) had the highest number of affected modalities. The children who were classified in an « autistic features » subgroup had the lowest number of affected modalities. There were no group differences in number of affected sensory modalities between groups of different cognitive levels or level of expressive speech. The findings provide support for the notion that sensory abnormality is very common in young children with autism. This symptom has been proposed for inclusion among the diagnostic criteria for ASD in the upcoming DSM-V.
21. Lemon JM, Gargaro B, Enticott PG, Rinehart NJ. {{Brief report: executive functioning in autism spectrum disorders: a gender comparison of response inhibition}}. {J Autism Dev Disord};2011 (Mar);41(3):352-356.
Although autism spectrum disorders (ASD) affect more males than females, it is not clear whether neurobehavioural correlates of ASD are equivalent across genders. This study examined gender differences in neurobehavioural functioning in boys and girls with ASD. Participants were males with ASD (n = 10), females with ASD (n = 13), typically developing males (n = 8), and typically developing females (n = 14). Each completed the stop task, a common measure of response inhibition. Females with ASD demonstrated a significant increase in stopping time (indicating poorer inhibition). By contrast, no response inhibition impairments were evident among males with ASD. Females with ASD may have a different neurobehavioural profile, and therefore different clinical needs, when compared with males with ASD.
22. Magiati I, Moss J, Yates R, Charman T, Howlin P. {{Is the Autism Treatment Evaluation Checklist a useful tool for monitoring progress in children with autism spectrum disorders?}}. {J Intellect Disabil Res};2011 (Mar);55(3):302-312.
Background There are few well validated brief measures that can be used to assess the general progress of young children with autism spectrum disorders (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist (ATEC) was used as part of a comprehensive assessment battery to monitor the progress of 22 school-aged children with ASD who had previously taken part in intensive home- or school-based intervention programmes in their pre-school years. Methods Parents completed the ATEC when the children were on average 5.5 years and then again 5-6 years later (mean age 10.4 years). Standardised measures were also used to assess cognitive, language and adaptive behaviour skills and severity of autism symptoms over the same period. Results The ATEC had high internal consistency at both time points. ATEC total and sub-scale scores remained relatively stable over time and were highly and significantly correlated with cognitive, language and adaptive behaviour skills and severity of autism symptoms at both assessment points. Initial ATEC total scores predicted 64% of the variance in scores at the subsequent follow-up. However, there was also considerable variation in the patterns of scores shown by individual children over time. Conclusions This study provides some preliminary evidence of the ATEC’s potential value for monitoring progress of children with ASD over time. Its advantages and limitations are discussed in the context of the need systematically to monitor the progress of children with ASD over time or in response to intervention.
23. Manning MM, Wainwright L, Bennett J. {{The Double ABCX Model of Adaptation in Racially Diverse Families with a School-Age Child with Autism}}. {J Autism Dev Disord};2011 (Mar);41(3):320-331.
In this study, the Double ABCX model of family adaptation was used to explore the impact of severity of autism symptoms, behavior problems, social support, religious coping, and reframing, on outcomes related to family functioning and parental distress. The sample included self-report measures collected from 195 families raising school-age children with autism from racially diverse backgrounds throughout the United States. Hierarchical regression results revealed that the Double ABCX model of family adaptation accounted for a substantial amount of the variance in family functioning (28%) and parental distress (46%). Findings suggest that child behavior problems and reframing are most strongly associated with family outcomes. Clinical implications for working with these families, including the use of strength-based approaches, are discussed.
24. 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};2011 (Mar-Apr);32(2):693-698.
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.
25. Napolioni V, Lombardi F, Sacco R, Curatolo P, Manzi B, Alessandrelli R, Militerni R, Bravaccio C, Lenti C, Saccani M, Schneider C, Melmed R, Pascucci T, Puglisi-Allegra S, Reichelt KL, Rousseau F, Lewin P, Persico AM. {{Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes}}. {Eur J Hum Genet};2011 (Mar);19(3):353-359.
The integrin-beta 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are significantly associated with autism (HBAT, global P=0.038). Haplotype H3 is largely over-transmitted to the affected offspring and doubles the risk of an ASD diagnosis (HBAT P=0.005; odds ratio (OR)=2.000), at the expense of haplotype H1, which is under-transmitted (HBAT P=0.018; OR=0.725). These two common haplotypes differ only at rs12603582 located in intron 11, which reaches a P-value of 0.072 in single-marker FBAT analyses. Interestingly, rs12603582 is strongly associated with pre-term delivery in our ASD patients (P=0.008). On the other hand, it is SNP rs2317385, located at the 5′ end of the gene, that significantly affects 5-HT blood levels (Mann-Whitney U-test, P=0.001; multiple regression analysis, P=0.010). No gene-gene interaction between ITGB3 and SLC6A4 has been detected. In conclusion, we identify a significant association between a common ITGB3 haplotype and ASD. Distinct markers, located toward the 5′ and 3′ ends of the gene, seemingly modulate 5-HT blood levels and autism liability, respectively. Our results also raise interest into ITGB3 influences on feto-maternal immune interactions in autism.
26. Papavasiliou AS, Nikaina I, Rizou J, Alexandrou S. {{The effect of a psycho-educational program on CARS scores and short sensory profile in autistic children}}. {Eur J Paediatr Neurol};2011 (Feb 25)
There is great demand for effective management of children with Autistic Spectrum Disorders (ASD). This study aimed to investigate the effect of an individually tailored psycho-educational program for autistic children on the scores of the Childhood Autism Rating Scale (CARS) and the Short Sensory Profile (SSP). METHODS: Forty children (36 males) were enrolled into an intervention program which consisted of occupational therapy including sensory integration techniques, speech therapy, social skills therapy and parent-directed approaches. Autism severity was assessed using CARS; sensory response capability with the SSP pre- and post-treatment. RESULTS: Eight children were intellectually normal; 12 borderline and 20 of low intelligence. Pre-treatment CARS showed that 8 were mildly autistic, 32 moderately-severely autistic. Post-treatment, 24 children changed category; 11 were no longer autistic. The percentage of children performing in the definitive difference region, according to total SSP score, changed slightly (45% vs 32.5%). Comparison of the pre- and post-treatment values revealed that CARS decreased significantly (p<0.001), whereas total SSP did not (p=0.294). Tactile sensitivity and low energy/weakness sections, though, were significantly different pre- and post-treatment. Longitudinal analysis, taking into account other confounding factors besides time, further revealed a significant decrement for CARS score with time but not for SSP score (p<0.001 and p=0.288, respectively). Similarly, intelligence levels affected CARS but not SSP values (p<0.001 and p=0.813, respectively). CONCLUSION: Individually tailored psycho-educational therapy had a significant effect on autism severity according to CARS. Changes in the SSP scores were not significant.
27. Parr JR, Le Couteur A, Baird G, Rutter M, Pickles A, Fombonne E, Bailey AJ. {{Early Developmental Regression in Autism Spectrum Disorder: Evidence from an International Multiplex Sample}}. {J Autism Dev Disord};2011 (Mar);41(3):332-340.
The characteristics of early developmental regression (EDR) were investigated in individuals with ASD from affected relative pairs recruited to the International Molecular Genetic Study of Autism Consortium (IMGSAC). Four hundred and fifty-eight individuals with ASD were recruited from 226 IMGSAC families. Regression before age 36 months occurred in 23.9% of individuals. The observed concordance rate for EDR within sibling pairs (18.9%) was not significantly above the rate expected under independence (13.5%, p = 0.10). The rate of regression in individuals with ASD from multiplex families was similar to that reported in singleton and epidemiological samples. Regression concordance data were not supportive of a separate familial influence on EDR, other than as a part of autism itself.
28. Pearson BL, Pobbe RL, Defensor EB, Oasay L, Bolivar VJ, Blanchard DC, Blanchard RJ. {{Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism}}. {Genes Brain Behav};2011 (Mar);10(2):228-235.
The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior.
29. Puleo CM, Kendall PC. {{Anxiety disorders in typically developing youth: autism spectrum symptoms as a predictor of cognitive-behavioral treatment}}. {J Autism Dev Disord};2011 (Mar);41(3):275-286.
Symptoms of autism spectrum disorder (ASD) were assessed (Social Responsiveness Scale-Parent (SRS-P); coded in-session behavior) in typically-developing, anxiety-disordered children (N = 50) treated with cognitive-behavioral therapy (CBT). Study 1: children with moderate autistic symptomology (per SRS-P) were significantly more likely to improve from family CBT (FCBT) than individual CBT (ICBT; OR = 8.67). Coded behavior did not predict outcome. Study 2: CBT components were compared by treatment and ASD symptom status. At-home exposure completion was greater in FCBT and there was an interaction in child involvement for treatment and ASD status. Though both treatments reduced anxiety, FCBT outperformed ICBT for children with moderate ASD symptoms, a benefit potentially linked to more at-home exposures and greater child involvement in FCBT.
30. Rozga A, Hutman T, Young GS, Rogers SJ, Ozonoff S, Dapretto M, Sigman M. {{Behavioral profiles of affected and unaffected siblings of children with autism: contribution of measures of mother-infant interaction and nonverbal communication}}. {J Autism Dev Disord};2011 (Mar);41(3):287-301.
We investigated whether deficits in social gaze and affect and in joint attention behaviors are evident within the first year of life among siblings of children with autism who go on to be diagnosed with autism or ASD (ASD) and siblings who are non-diagnosed (NoASD-sib) compared to low-risk controls. The ASD group did not differ from the other two groups at 6 months of age in the frequency of gaze, smiles, and vocalizations directed toward the caregiver, nor in their sensitivity to her withdrawal from interaction. However, by 12 months, infants in the ASD group exhibited lower rates of joint attention and requesting behaviors. In contrast, NoASD-sibs did not differ from comparison infants on any variables of interest at 6 and 12 months.
31. Sajdel-Sulkowska EM, Xu M, McGinnis W, Koibuchi N. {{Brain Region-Specific Changes in Oxidative Stress and Neurotrophin Levels in Autism Spectrum Disorders (ASD)}}. {Cerebellum};2011 (Mar);10(1):43-48.
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by social and language deficits, stereotypic behavior, and abnormalities in motor functions. The particular set of behavioral impairments expressed in any given individual is variable across the spectrum. These behavioral abnormalities are consistent with our current understanding of the neuropathology of ASD which suggests abnormalities in the amygdala, temporal and frontal cortexes, hippocampus, and cerebellum. However, regions unrelated to these behavioral deficits appear largely intact. Both genetic predisposition and environmental toxins and toxicants have been implicated in the etiology of autism; the impact of these environmental triggers is associated with increases in oxidative stress, and is further exacerbated when combined with genetic susceptibility. We have previously reported increased levels of 3-nitrotyrosine (3-NT), a marker of oxidative stress, in ASD cerebella. We have also shown that this increase was associated with an elevation in neurotrophin-3 (NT-3) levels. The objectives of the current study were to determine whether the increase in oxidative stress in ASD is brain region-specific, to identify the specific brain regions affected by oxidative stress, and to compare brain region-specific NT-3 expression between ASD and control cases. The levels of 3-NT and NT-3 were measured with specific ELISAs in individual brain regions of two autistic and age- and postmortem interval (PMI)–matched control donors. In the control brain, the levels of 3-NT were uniformly low in all brain regions examined ranging from 1.6 to 12.0 pmol/g. On the other hand, there was a great variation in 3-NT levels between individual brain regions of the autistic brains ranging from 1.7 to 281.2 pmol/g. The particular brain regions with the increased 3-NT and the magnitude of the increase were both different in the two autistic cases. In the older autistic case, the brain regions with highest levels of 3-NT included the orbitofrontal cortex (214.5 pmol/g), Wernicke’s area (171.7 pmol/g), cerebellar vermis (81.2 pmol/g), cerebellar hemisphere (37.2 pmol/g), and pons (13.6 pmol/g); these brain areas are associated with the speech processing, sensory and motor coordination, emotional and social behavior, and memory. Brain regions that showed 3-NT increase in both autistic cases included the cerebellar hemispheres and putamen. Consistent with our earlier report, we found an increase in NT-3 levels in the cerebellar hemisphere in both autistic cases. We also detected an increase in NT-3 level in the dorsolateral prefrontal cortex (BA46) in the older autistic case and in the Wernicke’s area and cingulate gyrus in the younger case. These preliminary results reveal, for the first time, brain region-specific changes in oxidative stress marker 3-NT and neurotrophin-3 levels in ASD.
32. Samyn V, Roeyers H, Bijttebier P. {{Effortful control in typically developing boys and in boys with ADHD or autism spectrum disorder}}. {Res Dev Disabil};2011 (Mar-Apr);32(2):483-490.
Despite increased interest in the role of effortful control (EC) in developmental disorders, few studies have focused on EC in autism spectrum disorders (ASD) and no study so far has directly compared children with ASD and children with ADHD. A first aim of this study was to investigate whether typically developing (TD) boys, boys with ADHD and boys with ASD can be differentiated based on EC levels. A second aim was to evaluate the relationship between EC and symptoms of ADHD and ASD. We assessed EC in 27 TD boys, 27 boys with ADHD and 27 boys with ASD (age 10-15) using different EC questionnaires. Clinical groups scored lower than the TD group on all EC total scales, but could only be differentiated from each other by means of self-reported persistence, impulsivity and activation control. Our data suggest that although EC is useful in differentiating TD boys from clinical groups, it is less efficient in distinguishing ADHD from ASD. Also, results suggest that EC plays a role in the manifestation of symptoms of both ADHD and ASD and that high levels of EC enable children to function more adequate in daily situations.
33. Shen C, Zhao XL, Ju W, Zou XB, Huo LR, Yan W, Zou JH, Yan GD, Jenkins EC, Brown WT, Zhong N. {{A Proteomic Investigation of B Lymphocytes in an Autistic Family: A Pilot Study of Exposure to Natural Rubber Latex (NRL) May Lead to Autism}}. {J Mol Neurosci};2011 (Mar);43(3):443-452.
Autism is a multi-factorial neurodevelopmental disorder. We have investigated the molecular mechanism involved in a Chinese family with autism by a proteomic approach. Antibody chips containing 500 spots of human protein antibodies were used to screen for differentially expressed proteins in the peripheral B lymphocytes between autistic and non-autistic siblings in this family. Four proteins relevant to immuno-pathway, including IKKalpha that was up-regulated and Tyk2, EIF4G1 and PRKCI that were down-regulated, were identified differentially expressed in autistic versus non-autistic siblings. Western blot analysis and reverse transcription quantitative polymerase chain reaction validated the differential expression of these four proteins. Based on the function of these differentially expressed proteins, relevant studies on immunoglobulin E (IgE) level, nuclear factor kappa B signaling activation and cell cycle were conducted in both autistic and non-autistic children of this family. Considering the fact that the family members were in close contact with natural rubber latex (NRL) and that IgE-mediated cross-reactions could be triggered by Hevea brasiliensis (Hev-b) proteins in NRL, we hypothesize that immune reactions triggered by close contact with NRL might influence the functions of B lymphocytes by altering expression of certain proteins identified in our experiments thus contributing to the occurrence of autism.
34. Shukla DK, Keehn B, Muller RA. {{Tract-specific analyses of diffusion tensor imaging show widespread white matter compromise in autism spectrum disorder}}. {J Child Psychol Psychiatry};2011 (Mar);52(3):286-295.
Background: Previous diffusion tensor imaging (DTI) studies have shown white matter compromise in children and adults with autism spectrum disorder (ASD), which may relate to reduced connectivity and impaired function of distributed networks. However, tract-specific evidence remains limited in ASD. We applied tract-based spatial statistics (TBSS) for an unbiased whole-brain quantitative estimation of the fractional anisotropy (FA), mean diffusion (MD) and axial and radial diffusion of the white matter tracts in children and adolescents with ASD. Methods: DTI was performed in 26 ASD and 24 typically developing (TD) participants, aged 9-20 years. Groups were matched for age and IQ. Each participant’s aligned FA, MD and axial and radial diffusion data were projected onto the mean FA skeleton representing the centers of all tracts and the resulting data fed into voxelwise group statistics. Results: TBSS revealed decreased FA and increased MD and radial diffusion in the ASD group compared to the TD group in the corpus callosum, anterior and posterior limbs of the internal capsule, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, cingulum, anterior thalamic radiation, and corticospinal tract. No single site with inverse effects (increased FA, reduced MD or radial diffusion in the ASD group) was detected. In clusters of significant group difference, age was positively correlated with FA and negatively correlated with MD and radial diffusion in the TD, but not the ASD group. Conclusions: Our findings reveal white matter compromise affecting numerous tracts in children and adolescents with ASD. Slightly varying patterns of diffusion abnormalities detected for some tracts may suggest tract-specific patterns of white matter abnormalities associated with ASD. Age-dependent effects further show that maturational changes (increasing FA, decreasing MD and radial diffusion with age) are diminished in ASD from school-age childhood into young adulthood.
35. Smith T, Eikeseth S. {{O. Ivar lovaas: pioneer of applied behavior analysis and intervention for children with autism}}. {J Autism Dev Disord};2011 (Mar);41(3):375-378.
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.
36. Snow AV, Lecavalier L. {{Comparing Autism, PDD-NOS, and Other Developmental Disabilities on Parent-Reported Behavior Problems: Little Evidence for ASD Subtype Validity}}. {J Autism Dev Disord};2011 (Mar);41(3):302-310.
Studies on the distinction between Autistic Disorder (AD) and Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) have been inconclusive. This study examined the validity of PDD-NOS by comparing it to AD and other developmental disorders (DD) on parent-reported behavior problems. Fifty-four children with PDD-NOS were individually matched on age and non-verbal IQ to 54 children with AD and 54 children with DD. Groups were compared on select subscales of the Child Behavior Checklist. High rates of psychopathology were observed in both ASD groups. The only difference between PDD-NOS and AD groups was higher scores in the PDD-NOS group on two items measuring Anxiety/Depression. Cognitive functioning may be a more salient variable than subtype when studying psychopathology in individuals with ASDs.
37. Stanley-Cary C, Rinehart N, Tonge B, White O, Fielding J. {{Greater Disruption to Control of Voluntary Saccades in Autistic Disorder than Asperger’s Disorder: Evidence for Greater Cerebellar Involvement in Autism?}}. {Cerebellum};2011 (Mar);10(1):70-80.
It remains unclear whether autism and Asperger’s disorder (AD) exist on a symptom continuum or are separate disorders with discrete neurobiological underpinnings. In addition to impairments in communication and social cognition, motor deficits constitute a significant clinical feature in both disorders. It has been suggested that motor deficits and in particular the integrity of cerebellar modulation of movement may differentiate these disorders. We used a simple volitional saccade task to comprehensively profile the integrity of voluntary ocular motor behaviour in individuals with high functioning autism (HFA) or AD, and included measures sensitive to cerebellar dysfunction. We tested three groups of age-matched young males with normal intelligence (full scale, verbal, and performance IQ estimates >70) aged between 11 and 19 years; nine with AD, eight with HFA, and ten normally developing males as the comparison group. Overall, the metrics and dynamics of the voluntary saccades produced in this task were preserved in the AD group. In contrast, the HFA group demonstrated relatively preserved mean measures of ocular motricity with cerebellar-like deficits demonstrated in increased variability on measures of response time, final eye position, and movement dynamics. These deficits were considered to be consistent with reduced cerebellar online adaptation of movement. The results support the notion that the integrity of cerebellar modulation of movement may be different in AD and HFA, suggesting potentially differential neurobiological substrates may underpin these complex disorders.
38. Sumiyoshi C, Kawakubo Y, Suga M, Sumiyoshi T, Kasai K. {{Impaired ability to organize information in individuals with autism spectrum disorders and their siblings}}. {Neurosci Res};2011 (Mar);69(3):252-257.
Despite rigorous research on disturbances of executive function and social cognition in autism spectrum disorders (ASD), little information has been available concerning higher cognitive functions, such as the ability to focus and associate relevant features to form categories, or ‘organizing of information’. The purpose of this study was to investigate this issue by using the Wisconsin Card Sorting Test (WCST) and the Verbal Learning Task (VLT). Cognitive assessments were conducted in 22 individuals with ASD, 14 non-affected siblings, and 15 age-matched control subjects. Overall, individuals with ASD performed significantly worse on the WCST and VLT compared to their siblings and normal control subjects. Although siblings performed generally well on both tasks, they exhibited similar degree of perseverative responses in the WCST compared to the probands. A linear increase of the memory organization score in the VLT was also absent in siblings as well as the ASD group. These results suggest an impaired ability to organize information is one of the cognitive endophenotypes for ASD.
39. Trembath D. {{Book Review Editor: Rachel Mayes Autism Spectrum Disorders and AAC. Pat Mirenda & Teresa Iacono (Eds.) Baltimore, MD : Brookes . 2009 . 504 pp. US$49.95 . ISBN: 978-1-55766-953-7}}. {J Intellect Dev Disabil};2011 (Mar);36(1):84-85.
40. von dem Hagen EA, Nummenmaa L, Yu R, Engell AD, Ewbank MP, Calder AJ. {{Autism spectrum traits in the typical population predict structure and function in the posterior superior temporal sulcus}}. {Cereb Cortex};2011 (Mar);21(3):493-500.
Autism spectrum disorders (ASDs) are typically characterized by impaired social interaction and communication, narrow interests, and repetitive behaviors. The heterogeneity in the severity of these characteristics across individuals with ASD has led some researchers to suggest that these disorders form a continuum which extends into the general, or « typical, » population, and there is growing evidence that the extent to which typical adults display autistic traits, as measured using the autism-spectrum quotient (AQ), predicts performance on behavioral tasks that are impaired in ASD. Here, we show that variation in autism spectrum traits is related to cortical structure and function within the typical population. Voxel-based morphometry showed that increased AQ scores were associated with decreased white matter volume in the posterior superior temporal sulcus (pSTS), a region important in processing socially relevant stimuli and associated with structural and functional impairments in ASD. In addition, AQ was correlated with the extent of cortical deactivation of an adjacent area of pSTS during a Stroop task relative to rest, reflecting variation in resting state function. The results provide evidence that autism spectrum characteristics are reflected in neural structure and function across the typical (non-ASD) population.
41. Weng SJ, Carrasco M, Swartz JR, Wiggins JL, Kurapati N, Liberzon I, Risi S, Lord C, Monk CS. {{Neural activation to emotional faces in adolescents with autism spectrum disorders}}. {J Child Psychol Psychiatry};2011 (Mar);52(3):296-305.
Background: Autism spectrum disorders (ASD) involve a core deficit in social functioning and impairments in the ability to recognize face emotions. In an emotional faces task designed to constrain group differences in attention, the present study used functional MRI to characterize activation in the amygdala, ventral prefrontal cortex (vPFC), and striatum, three structures involved in socio-emotional processing in adolescents with ASD. Methods: Twenty-two adolescents with ASD and 20 healthy adolescents viewed facial expressions (happy, fearful, sad and neutral) that were briefly presented (250 ms) during functional MRI acquisition. To monitor attention, subjects pressed a button to identify the gender of each face. Results: The ASD group showed greater activation to the faces relative to the control group in the amygdala, vPFC and striatum. Follow-up analyses indicated that the ASD relative to control group showed greater activation in the amygdala, vPFC and striatum (p < .05 small volume corrected), particularly to sad faces. Moreover, in the ASD group, there was a negative correlation between developmental variables (age and pubertal status) and mean activation from the whole bilateral amygdala; younger adolescents showed greater activation than older adolescents. There were no group differences in accuracy or reaction time in the gender identification task. Conclusions: When group differences in attention to facial expressions were limited, adolescents with ASD showed greater activation in structures involved in socio-emotional processing.
42. Werner S. {{Assessing female students’ attitudes in various health and social professions toward working with people with autism: A preliminary study}}. {J Interprof Care};2011 (Mar);25(2):131-137.
A range of professionals needs to work collaboratively in providing services for the growing numbers of people diagnosed with autism. Given the challenges of recruiting health professionals to work with people with disabilities in general, it is important to understand the factors that affect students’ choices about working with people with autism, in particular. The aim of the present study was to assess attitudes of students in various health and social professions toward working with people with autism. An elicitation study based on the theory of planned behavior was conducted among 42 female students from the departments of social work, education, nursing, occupational therapy, and communication disorders/speech and language therapy. Working with people with autism was perceived as difficult, challenging, and frustrating, yet rewarding, important, and an opportunity to develop personally and professionally. Furthermore, the importance of awareness to stigmatic beliefs was raised. Familiarity, knowledge, and training were perceived as important. The results call for increasing university curriculum in the area of autism, increasing the contact of students with this population and focusing on training in interprofessional collaboration.
43. Wing L, Gould J, Gillberg C. {{Autism spectrum disorders in the DSM-V: Better or worse than the DSM-IV?}}. {Res Dev Disabil};2011 (Mar-Apr);32(2):768-773.
The DSM-V-committee has recently published proposed diagnostic criteria for autism spectrum disorders. We examine these criteria in some detail. We believe that the DSM-committee has overlooked a number of important issues, including social imagination, diagnosis in infancy and adulthood, and the possibility that girls and women with autism may continue to go unrecognised or misdiagnosed under the new manual. We conclude that a number of changes need to be made in order that the DSM-V-criteria might be used reliably and validly in clinical practice and research.
