1. Allen-Brady K, Miller J, Matsunami N, Stevens J, Block H, Farley M, Krasny L, Pingree C, Lainhart J, Leppert M, McMahon WM, Coon H. {{A high-density SNP genome-wide linkage scan in a large autism extended pedigree}}. {Mol Psychiatry};2009 (Jun);14(6):590-600.
We performed a high-density, single nucleotide polymorphism (SNP), genome-wide scan on a six-generation pedigree from Utah with seven affected males, diagnosed with autism spectrum disorder. Using a two-stage linkage design, we first performed a nonparametric analysis on the entire genome using a 10K SNP chip to identify potential regions of interest. To confirm potentially interesting regions, we eliminated SNPs in high linkage disequilibrium (LD) using a principal components analysis (PCA) method and repeated the linkage results. Three regions met genome-wide significance criteria after controlling for LD: 3q13.2-q13.31 (nonparametric linkage (NPL), 5.58), 3q26.31-q27.3 (NPL, 4.85) and 20q11.21-q13.12 (NPL, 5.56). Two regions met suggestive criteria for significance 7p14.1-p11.22 (NPL, 3.18) and 9p24.3 (NPL, 3.44). All five chromosomal regions are consistent with other published findings. Haplotype sharing results showed that five of the affected subjects shared more than a single chromosomal region of interest with other affected subjects. Although no common autism susceptibility genes were found for all seven autism cases, these results suggest that multiple genetic loci within these regions may contribute to the autism phenotype in this family, and further follow-up of these chromosomal regions is warranted.
2. Altiere MJ, von Kluge S. {{Searching for acceptance: challenges encountered while raising a child with autism}}. {J Intellect Dev Disabil};2009 (Jun);34(2):142-152.
BACKGROUND: Autism, a severe childhood disorder, affects the family system in dramatic ways. METHOD: Fifty-two parents of children with autism were interviewed to explore their struggles and their successes qualitatively. RESULTS: Five challenges that emerged from these family’s experiences were: Development, Questioning, Devastation, Solutions, and Growth. Every parent described the confusion that resulted from their child’s behavioural presentation and the feelings of loss and devastation that occurred after discovering their child has autism. Parents, however, were swift and eager to mobilise resources to help their child, sometimes in any possible way. Almost every parent described significant, positive experiences that resulted from raising a child with autism, despite the hardships. CONCLUSIONS: The findings of this study provide important considerations for professionals and families.
3. Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE, Brayne C. {{Prevalence of autism-spectrum conditions: UK school-based population study}}. {Br J Psychiatry};2009 (Jun);194(6):500-509.
BACKGROUND: Recent reports estimate the prevalence of autism-spectrum conditions in the UK to be 1%. AIMS: To use different methods to estimate the prevalence of autism-spectrum conditions, including previously undiagnosed cases, in Cambridgeshire. METHOD: We carried out a survey of autism-spectrum conditions using the Special Educational Needs (SEN) register. A diagnosis survey was distributed to participating schools to be handed out to parents of all children aged 5-9 years. The mainstream primary school population was screened for unknown cases. RESULTS: The prevalence estimates generated from the SEN register and diagnosis survey were 94 per 10 000 and 99 per 10 000 respectively. A total of 11 children received a research diagnosis of an autism-spectrum condition following screening and assessment. The ratio of known:unknown cases is about 3:2 (following statistical weighting procedures). Taken together, we estimate the prevalence to be 157 per 10 000, including previously undiagnosed cases. CONCLUSIONS: This study has implications for planning diagnostic, social and health services.
4. Ben-Shachar S, Lanpher B, German JR, Qasaymeh M, Potocki L, Nagamani SC, Franco LM, Malphrus A, Bottenfield GW, Spence JE, Amato S, Rousseau JA, Moghaddam B, Skinner C, Skinner SA, Bernes S, Armstrong N, Shinawi M, Stankiewicz P, Patel A, Cheung SW, Lupski JR, Beaudet AL, Sahoo T. {{Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders}}. {J Med Genet};2009 (Jun);46(6):382-388.
BACKGROUND: Microdeletions within chromosome 15q13.3 are associated both with a recently recognised syndrome of mental retardation, seizures, and dysmorphic features, and with schizophrenia. METHODS AND RESULTS: Based on routine diagnostic testing of approximately 8200 samples using array comparative genomic hybridisation, we identified 20 individuals (14 children and six parents in 12 families) with microdeletions of 15q13.3. Phenotypes in the children included developmental delay, mental retardation, or borderline IQ in most and autistic spectrum disorder (6/14), speech delay, aggressiveness, attention deficit hyperactivity disorder, and other behavioural problems. Both parents were available in seven families, and the deletion was de novo in one, inherited from an apparently normal parent in four, and inherited from a parent with learning disability and bipolar disorder in two families. Of the 14 children, six in five families were adopted, and DNA was available for only one of these 10 biological parents; the deletion was very likely inherited for one of these families with two affected children. Among the unavailable parents, two mothers were described as having mental retardation, another mother as having « mental illness », and one father as having schizophrenia. We hypothesise that some of the unavailable parents have the deletion. CONCLUSIONS: The occurrence of increased adoption, frequent autism, bipolar disorder, and lack of penetrance are noteworthy findings in individuals with deletion 15q13.3. A high rate of adoption may be related to the presence of the deletion in biological parents. Unconfirmed histories of antisocial behaviours in unavailable biological parents raise the concern that future research may show that deletion 15q13.3 is associated with such behaviours.
5. Bouder JN, Spielman S, Mandell DS. {{Brief report: quantifying the impact of autism coverage on private insurance premiums}}. {J Autism Dev Disord};2009 (Jun);39(6):953-957.
Many states are considering legislation requiring private insurance companies to pay for autism-related services. Arguments against mandates include that they will result in higher premiums. Using Pennsylvania legislation as an example, which proposed covering services up to $36,000 per year for individuals less than 21 years of age, this paper estimates potential premium increases. The estimate relies on autism treated prevalence, the number of individuals insured by affected plans, mean annual autism expenditures, administrative costs, medical loss ratio, and total insurer revenue. Current treated prevalence and expenditures suggests that premium increases would approximate 1%, with a lower bound of 0.19% and an upper bound of 2.31%. Policy makers can use these results to assess the cost-effectiveness of similar legislation.
6. Bowler DM, Limoges E, Mottron L. {{Different verbal learning strategies in autism spectrum disorder: evidence from the Rey Auditory Verbal Learning Test}}. {J Autism Dev Disord};2009 (Jun);39(6):910-915.
The Rey Auditory Verbal Learning Test, which requires the free recall of the same list of 15 unrelated words over 5 trials, was administered to 21 high-functioning adolescents and adults with autism spectrum disorder (ASD) and 21 matched typical individuals. The groups showed similar overall levels of free recall, rates of learning over trials and subjective organisation of their recall. However, the primacy portion of the serial position curve of the ASD participants showed slower growth over trials than that of the typical participants. The implications of this finding for our understanding of memory in ASD are discussed.
7. Campbell DB. {{When linkage signal for autism MET candidate gene}}. {Eur J Hum Genet};2009 (Jun);17(6):699-700.
8. Chan AS, Cheung MC, Han YM, Sze SL, Leung WW, Man HS, To CY. {{Executive function deficits and neural discordance in children with Autism Spectrum Disorders}}. {Clin Neurophysiol};2009 (Jun);120(6):1107-1115.
OBJECTIVE: This study examined neurophysiologic activities, executive dysfunctions, and their association in children with Autism Spectrum Disorders (ASD). METHODS: Thirty-eight normal and 16 children with ASD participated with parental consent. Executive functions were measured using neuropsychological tests and parent ratings, and neurophysiologic activities were measured using EEG to yield cordance values, an indirect measure of brain perfusion. RESULTS: Children with ASD made significantly more intrusion errors and False Alarms on the Hong Kong List Learning Test (HKLLT) and Object Recognition Test (OR) than normal children, but were comparable to normal children on the Rey-Osterrieth Complex Figure Test and Continuous Performance Test. They also showed significantly poorer executive functions in everyday activities as shown on the Behavior Rating Inventory of Executive Function (BRIEF), and had lower frontal perfusion patterns than normal children as shown in the neurophysiologic cordance measures. Frontal cordance values were found to be significantly associated with executive dysfunctions in HKLLT Delayed Intrusions, OR False Alarms and BRIEF. CONCLUSIONS: Children with ASD were impaired in everyday executive functioning and response inhibition. The cordance value, which has been shown to correlate with brain perfusion in a number of studies, was significantly correlated with executive dysfunctions. SIGNIFICANCE: Exploration of this measure as an index for response to intervention is warranted.
9. Dawson S, Glasson EJ, Dixon G, Bower C. {{Birth defects in children with autism spectrum disorders: a population-based, nested case-control study}}. {Am J Epidemiol};2009 (Jun 1);169(11):1296-1303.
The causes of autism spectrum disorders (ASDs) are unknown, although genetic and environmental influences have been implicated. Previous studies have suggested an association with birth defects, but most investigators have not addressed associations with specific diagnostic categories of ASD. In this study, the authors investigated the associations between birth defects and autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified. Using Western Australian population-based linked data, the authors compared all children with ASD born in Western Australia during 1980-1995 (n = 465) with their siblings (n = 481) and population controls (n = 1,313) in a nested case-control study. The prevalence of birth defects was significantly higher in ASD cases than in population controls; this difference remained significant after adjustment for confounding factors. Odds ratios for birth defects were similar for autism (odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.0) and pervasive developmental disorder not otherwise specified (OR = 2.2, 95% CI: 1.1, 4.3) but not for Asperger syndrome (OR = 0.5, 95% CI: 0.1, 1.9). Birth defects in case siblings were not significantly different from those in cases and population controls. The association between birth defects and ASD may be due to underlying genetic and/or environmental factors common to both ASD and birth defects, or birth defects may predispose a child to ASD.
10. Dillenburger K, Keenan M. {{None of the As in ABA stand for autism: dispelling the myths}}. {J Intellect Dev Disabil};2009 (Jun);34(2):193-195.
11. d’Orsi G, Demaio V, Minervini MG. {{Myoclonic status misdiagnosed as movement disorders in Rett syndrome: a video-polygraphic study}}. {Epilepsy Behav};2009 (Jun);15(2):260-262.
Myoclonic jerks and myoclonic status (MS) are sometimes difficult to distinguish clinically from movement disorders such as hand stereotypies, tremor, and dystonia in Rett syndrome. We describe a rare and complete video-polygraphic study of a girl with Rett syndrome (MECP2 mutation) and MS misdiagnosed as movement disorders and disclosed after video-polygraphic recordings. Corresponding to closely recurring activity of diffuse spike and polyspikes-wave-type paroxysms, rhythmic and, especially, arrhythmic myoclonias, usually asymmetrical and asynchronous, involving mainly right muscle deltoid and rarely followed by an inhibitory phenomenon, appeared. The MS improved and, most importantly, disappeared after the use of levetiracetam, with an evident antimyoclonic efficacy and a marked improvement of daily life for the patient and her caregivers. The difficulty in differentiating some typical nonepileptic behavioral features and movement disorders of patients with Rett syndrome from seizures was overcome using prolonged video-polygraphic recordings in our case.
12. Downs J, Young D, de Klerk N, Bebbington A, Baikie G, Leonard H. {{Impact of scoliosis surgery on activities of daily living in females with Rett syndrome}}. {J Pediatr Orthop};2009 (Jun);29(4):369-374.
BACKGROUND: Scoliosis is a common orthopaedic complication of Rett syndrome, and surgery is commonly used to reduce asymmetry in cases with severe scoliosis. METHODS: Data from questionnaires administered to caregivers biennially from 2000 to 2006 were used to describe functional skill levels in subjects with Rett syndrome, and within-subject change in 16 subjects with scoliosis surgery were compared with within-subject change in 186 pairs of data from 86 subjects with conservatively managed scoliosis. Postsurgical assessment was conducted after a mean of 17.8 months. RESULTS: Surgery was associated with improved activities of daily living as measured by the WeeFIM for subjects who were wheelchair bound (P = 0.05). Mobility levels, social interaction, communication skills, and the frequency of daytime napping remained similar for the group as a whole. CONCLUSIONS: Improvements in activities of daily living are likely to represent an increase in the quality of life for subjects and caregivers and were mainly found in subjects who were wheelchair bound, indicating that those who were more severely affected were able to benefit from this intervention. LEVEL OF EVIDENCE: Therapeutic study: level III.
13. Finke EH, McNaughton DB, Drager KD. {{« All children can and should have the opportunity to learn »: general education teachers’ perspectives on including children with autism spectrum disorder who require AAC}}. {Augment Altern Commun};2009 (Jun);25(2):110-122.
A qualitative online focus group methodology was used to investigate the experiences of five elementary school teachers (grades K-5) who had included in their general education classrooms children with autism spectrum disorders (ASD) who required augmentative and alternative communication (AAC). Information was obtained from the participants in the following areas: (a) the benefits of educational inclusion, (b) the negative impacts of educational inclusion, (c) the challenges of educational inclusion, (d) the supports for educational inclusion, and (e) recommendations for other teachers and individuals involved in the inclusion process. Participants primarily chose to focus on inclusion as a beneficial practice for all involved, but did describe a few barriers and challenges of inclusion. The results are discussed as they relate to these themes and with reference to published literature. Recommendations for future directions are also presented.
14. Fodstad JC, Matson JL, Hess J, Neal D. {{Social and communication behaviours in infants and toddlers with autism and pervasive developmental disorder-not otherwise specified}}. {Dev Neurorehabil};2009 (Jun);12(3):152-157.
PURPOSE: Autism Spectrum Disorders (ASD) are a group of conditions characterized by symptoms that onset in early childhood. Deficits in social skills and communication are two of the core features of ASD and, if not remediated, can lead to poor long-term outcomes. Few researchers have examined characteristics of social skills and communication in infants with ASD. METHOD: The social skills and communicative ability of 886 infants and toddlers 17-37 months of age with autism, PDD-NOS or ‘at risk’ for other developmental delays were evaluated using the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). A Kruskal-Wallis test with follow-up Mann-Whitney tests were used to test for significance. RESULTS: Infants and toddlers with autism, followed by PDD-NOS, had greater social and communication deficits than children ‘at risk’ for developmental delays. Items which distinguished between these diagnostic groups were determined. CONCLUSIONS: Outcomes suggest that social and communication deficits can be identified at early ages in a population of developmentally delayed toddlers. Implications are that pinpointing emerging social and communicative autistic traits earlier will allow for more accurate assessment and diagnosis in infants with ASD. This translates into earlier intervention and more effective treatment practices.
15. Fombonne E. {{Epidemiology of pervasive developmental disorders}}. {Pediatr Res};2009 (Jun);65(6):591-598.
This article reviews the results of 43 studies published since 1966 that provided estimates for the prevalence of pervasive developmental disorders (PDDs), including autistic disorder, Asperger disorder, PDD not otherwise specified, and childhood disintegrative disorder. The prevalence of autistic disorder has increased in recent surveys and current estimates of prevalence are around 20/10,000, whereas the prevalence for PDD not otherwise specified is around 30/10,000 in recent surveys. Prevalence of Asperger disorder is much lower than that for autistic disorder and childhood disintegrative disorder is a very rare disorder with a prevalence of about 2/100,000. Combined all together, recent studies that have examined the whole spectrum of PDDs have consistently provided estimates in the 60-70/10,000 range, making PDD one of the most frequent childhood neurodevelopmental disorders. The meaning of the increase in prevalence in recent decades is reviewed. There is evidence that the broadening of the concept, the expansion of diagnostic criteria, the development of services, and improved awareness of the condition have played a major role in explaining this increase, although it cannot be ruled out that other factors might have also contributed to that trend.
16. Gerhard T, Chavez B, Olfson M, Crystal S. {{National patterns in the outpatient pharmacological management of children and adolescents with autism spectrum disorder}}. {J Clin Psychopharmacol};2009 (Jun);29(3):307-310.
17. Hallett V, Ronald A, Happe F. {{Investigating the association between autistic-like and internalizing traits in a community-based twin sample}}. {J Am Acad Child Adolesc Psychiatry};2009 (Jun);48(6):618-627.
OBJECTIVES: Recent research has suggested that children with autistic spectrum disorders often experience comorbid symptoms of anxiety and depression. However, despite this overlap, no quantitative genetic studies have addressed the phenotypic overlap and the etiologic association between internalizing and autistic-like traits within the general population. This study aimed to investigate the phenotypic and etiologic relation between internalizing and autistic-like traits using a community-based twin sample. METHOD: We investigated the co-occurrence of these traits in a population-based sample of 3,233 twin pairs aged 8 to 9 years, using both parent- and teacher-report questionnaires. Bivariate structural equation modeling techniques were used to determine the extent to which internalizing and autistic-like traits shared common genetic and environmental influences. RESULTS: Our results showed that there was a modest phenotypic correlation (r = 0.26-0.29) between autistic-like and internalizing traits. The traits were both substantially heritable but were largely independent with regard to their genetic influences (r(G) = 0.12-0.19). Shared environmental influences were modest but were largely common to both traits. Similar results were found using both parent- and teacher-reported data. CONCLUSIONS: Internalizing and autistic-like traits showed moderate phenotypic overlap within the general population. This association was explained in small part by shared genetic factors, but the results suggested that most genetic influences were specific to either internalizing traits or autistic traits. Given these findings, we discuss the potential mechanisms that may underlie the relation between these traits.
18. Henningsson S, Jonsson L, Ljunggren E, Westberg L, Gillberg C, Rastam M, Anckarsater H, Nygren G, Landen M, Thuresson K, Betancur C, Leboyer M, Gillberg C, Eriksson E, Melke J. {{Possible association between the androgen receptor gene and autism spectrum disorder}}. {Psychoneuroendocrinology};2009 (Jun);34(5):752-761.
Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon 1 of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results lend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition.
19. Herbrecht E, Poustka F, Birnkammer S, Duketis E, Schlitt S, Schmotzer G, Bolte S. {{Pilot evaluation of the Frankfurt Social Skills Training for children and adolescents with autism spectrum disorder}}. {Eur Child Adolesc Psychiatry};2009 (Jun);18(6):327-335.
The objective of this pilot study was to evaluate the effectiveness of a group-based intervention aiming at improving social and communication skills in individuals with autism spectrum disorder. Over a period of 11 months, N = 17 children and adolescents received treatment according to the manualised Frankfurt Social Skills Training (KONTAKT). Parent, teacher, expert and blind expert ratings were assessed to judge outcome regarding peer interaction, autistic behaviours, adaptive functioning and family burden. The participants exhibited improvements pre to follow-up treatment, particularly in the area of autistic symptomatology. Effect sizes (partial eta squared) ranged from 0.02 to 0.69. Among other things, regression models showed a positive influence of IQ and language skills on gains in social skills. Findings indicate that KONTAKT might be useful for enhancing social skills and reducing autism-related psychopathology over time in different contexts. Nevertheless, controlled trials are needed to reassure its effectiveness.
20. Hernandez RN, Feinberg RL, Vaurio R, Passanante NM, Thompson RE, Kaufmann WE. {{Autism spectrum disorder in fragile X syndrome: a longitudinal evaluation}}. {Am J Med Genet A};2009 (Jun);149A(6):1125-1137.
The present study extends our previous work on characterizing the autistic behavior profile of boys with fragile X syndrome (FXS) who meet Diagnostic and Statistical Manual for Mental Disorders, 4th Edition criteria for autism spectrum disorder (ASD) into a longitudinal evaluation of ASD in FXS (FXS + ASD). Specifically, we aimed to determine the stability of the diagnosis and profile of ASD in FXS over time. Through regression models, we also evaluated which autistic and social behaviors and skills were correlates of diagnosis and autistic behavior severity (i.e., Autism Diagnostic Interview-Revised total scores). Finally, we assessed the evolution of cognitive parameters in FXS + ASD. A population of 56 boys (30-88 months at baseline) with FXS was evaluated using measures of autistic, social, and cognitive behaviors and skills at three yearly evaluations. We found that the diagnosis of ASD in FXS was relatively stable over time. Further emphasizing this stability, we found a set of behaviors and skills, particularly those related to peer relationships and adaptive socialization, that differentiated FXS + ASD from the rest of the FXS cohort (FXS + None) and contributed to autistic severity at all time points. Nevertheless, the general improvement in autistic behavior observed in FXS + ASD coupled with the concurrent worsening in FXS + None resulted in less differentiation between the groups over time. Surprisingly, FXS + ASD IQ scores were stable while FXS + None non-verbal IQ scores declined. Our findings indicate that ASD is a distinctive subphenotype in FXS characterized by deficits in complex social interaction, with similarities to ASD in the general population.
21. Johnson WG, Buyske S, Mars AE, Sreenath M, Stenroos ES, Williams TA, Stein R, Lambert GH. {{HLA-DR4 as a Risk Allele for Autism Acting in Mothers of Probands Possibly During Pregnancy}}. {Arch Pediatr Adolesc Med};2009 (Jun);163(6):542-546.
OBJECTIVES: To test whether HLA-DR4 acts in the mother, possibly during pregnancy, to contribute to the phenotype of autistic disorder in her fetus. DESIGN: Transmission disequilibrium testing in case mothers and maternal grandparents. SETTING: Previous studies have consistently shown increased frequency of HLA-DR4 in probands with autism and their mothers, but not their fathers. However, this has been documented only in case-control studies and not by a more direct study design to determine whether HLA-DR4 acts in mothers during pregnancy to contribute to autism in their affected offspring. PARTICIPANTS: We genotyped for HLA-DR alleles in members of 31 families with parents and maternal grandparents. Probands with autism were tested using the Autism Diagnostic Observation Schedule-Western Psychological Services and Autism Diagnostic Interview, Revised. There was 80% power to detect an odds ratio of 3.6. Participants were all families from New Jersey and were similar in number to earlier studies of autism and HLA-DR4. OUTCOME MEASURES: Analysis was by standard transmission disequilibrium testing. As a secondary test we examined the possibility of maternal imprinting. RESULTS: Significant transmission disequilibrium for HLA-DR4 was seen (odds ratio, 4.67; 95% confidence interval, 1.34-16.24; P = .008) for transmissions from maternal grandparents to mothers of probands, supporting a role for HLA-DR4 as an autism risk factor acting in mothers during pregnancy. Transmission disequilibrium was not seen for HLA-DR4 transmissions from parents to probands or from mothers to probands. CONCLUSIONS: The HLA-DR4 gene may act in mothers of children with autism during pregnancy to contribute to autism in their offspring. Further studies are required to confirm these findings.
22. Johnston SS, Buchanan S, Davenport L. {{Comparison of fixed and gradual array when teaching sound-letter correspondence to two children with autism who use AAC}}. {Augment Altern Commun};2009 (Jun);25(2):136-144.
The purpose of this study was to compare two conditions for teaching two children with autism (ages 4;10 and 5;4) who used Augmentative and Alternative Communication (AAC) to point to the printed letter that corresponded to the spoken letter sounds of /t/ and /m/. In one condition (gradual array), the printed letter was first presented in isolation and then distracter letters were gradually introduced. In the other condition (fixed array), the printed letter was immediately presented in combination with seven distracter letters. Using an alternating treatment design, results revealed that the fixed array condition resulted in a faster rate of acquisition of target skills for both participants. Implications and directions for future research are discussed.
23. Kanne SM, Abbacchi AM, Constantino JN. {{Multi-informant ratings of psychiatric symptom severity in children with autism spectrum disorders: the importance of environmental context}}. {J Autism Dev Disord};2009 (Jun);39(6):856-864.
The present study examines co-occurring psychiatric syndromes in a well-characterized sample of youths with autism spectrum disorders (ASD; n = 177) and their siblings (n = 148), reported independently by parents and teachers. In ASD, parents reported substantial comorbidity with affective (26%), anxiety (25%), attentional (25%), conduct (16%), oppositional (15%), and somatic problems (6%). Teachers reported a much lower prevalence. Autistic severity scores for children with ASD exhibited moderate correlations with general psychopathology within- but not across-informants, whereas, sibling correlations were significant both within- and across-informants. Results support the role of environmental context in psychiatric symptom expression in children affected by autism and suggest that informant discrepancies may more provide critical cues for these children via specific environmental modifications.
24. Kanne SM, Christ SE, Reiersen AM. {{Psychiatric symptoms and psychosocial difficulties in young adults with autistic traits}}. {J Autism Dev Disord};2009 (Jun);39(6):827-833.
A screening version of the social responsiveness scale (SRS) was administered to 1,847 university students to identify a subgroup reporting significantly greater autism traits relative to their peers (High SRS group). A group reporting minimal autism traits was also identified (Low SRS group) matched for age, gender, and attentional difficulties. We administered the Behavioral Assessment System for Children-2nd edition (BASC-2), a comprehensive questionnaire designed to assess psychiatric symptoms and personality characteristics, to both groups. The high SRS group reported significantly more difficulties across the majority of areas, including depression/anxiety, interpersonal relationships, and personal adjustment. Thus, young adults reporting a greater degree of autistic traits also reported greater psychiatric difficulties across a wide psychosocial range.
25. Keary CJ, Minshew NJ, Bansal R, Goradia D, Fedorov S, Keshavan MS, Hardan AY. {{Corpus callosum volume and neurocognition in autism}}. {J Autism Dev Disord};2009 (Jun);39(6):834-841.
The corpus callosum has recently been considered as an index of interhemispheric connectivity. This study applied a novel volumetric method to examine the size of the corpus callosum in 32 individuals with autism and 34 age-, gender- and IQ-matched controls and to investigate the relationship between this structure and cognitive measures linked to interhemispheric functioning. Participants with autism displayed reductions in total corpus callosum volume and in several of its subdivisions. Relationships were also observed between volumetric alterations and performance on several cognitive tests including the Tower of Hanoi test. These findings provide further evidence for anatomical alterations in the corpus callosum in autism, but warrant additional studies examining the relationship of this structure and specific measures of interhemispheric connectivity.
26. King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, Donnelly CL, Anagnostou E, Dukes K, Sullivan L, Hirtz D, Wagner A, Ritz L, STAART Psychopharmacology Network. {{Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism}}. {Arch Gen Psychiatry};2009 (Jun);66(6):583-590.
CONTEXT: Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. OBJECTIVES: To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. DESIGN: National Institutes of Health-sponsored randomized controlled trial. SETTING: Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. PARTICIPANTS: One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children’s Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. INTERVENTIONS: Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). MAIN OUTCOME MEASURES: Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children’s Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. RESULTS: There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P > .99). There was no difference in score reduction on the Children’s Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. CONCLUSION: Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.
27. Kuusikko S, Haapsamo H, Jansson-Verkasalo E, Hurtig T, Mattila ML, Ebeling H, Jussila K, Bolte S, Moilanen I. {{Emotion recognition in children and adolescents with autism spectrum disorders}}. {J Autism Dev Disord};2009 (Jun);39(6):938-945.
We examined upper facial basic emotion recognition in 57 subjects with autism spectrum disorders (ASD) (M = 13.5 years) and 33 typically developing controls (M = 14.3 years) by using a standardized computer-aided measure (The Frankfurt Test and Training of Facial Affect Recognition, FEFA). The ASD group scored lower than controls on the total scores of FEFA and perceived ambiguous stimuli more often as a negative emotion. The older ASD group (> or =12 years) performed better than the younger ASD group (<12 years) on the blended emotions of FEFA. The results support the findings that individuals with ASD have difficulties in emotion recognition. However, older subjects with ASD seem to have better skills than younger subjects with ASD.
28. Kuwagata M, Ogawa T, Shioda S, Nagata T. {{Observation of fetal brain in a rat valproate-induced autism model: a developmental neurotoxicity study}}. {Int J Dev Neurosci};2009 (Jun);27(4):399-405.
Prenatal exposure to chemicals is well known to induce developmental abnormalities in the central nervous system of children. Developmental neurotoxicity (DNT) tests are important to identify neurotoxic agents and prevent neurodevelopmental disorders. We have investigated DNT, focusing on the fetal brain shortly after chemical exposure. To demonstrate a usefulness of a study focusing on the fetal brain in DNT tests, we assessed the fetal brain in a rat valproate-induced autism model. Rats were treated with sodium valproate (VPA, 800 mg/kg) orally on gestational day (GD) 9 or 11 (VPA9 or VPA11), and the fetal brains were examined on GD16 using immunohistochemistry for serotonin (5-HT), tyrosine hydroxylase (TH), and TuJ1 (neuron specific class III beta-tubulin). Hypoplasia of the cortical plate was induced in both VPA9 and VPA11 groups. Abnormal migration of TH-positive and 5-HT neurons, possibly due to the appearance of an abnormally running nerve tract in the pons, was observed only in the VPA11 group. In addition, when we compared the incidence of these abnormalities between pregnant rats mated in our own animal facility (in-house group), and rats purchased pregnant (supplier group), the supplier group was much more sensitive, especially to the pons abnormality. Shipping stress may affect the reproducibility of VPA-induced DNT. The present results demonstrate that examination of the GD16 fetal brain was useful for detecting and characterizing abnormal development of the brain after VPA exposure. Further discussion was made with reference to the findings in children with autism.
29. Leeming RJ, Lucock M. {{Autism: Is there a folate connection?}} {J Inherit Metab Dis};2009 (Jun);32(3):400-402.
Autism is increasing-but why? Birth defect prevention trials were based on the teleological assumption that folic acid could prevent neural tube defects without consideration of long-term effects, some of which could be beneficial, some of which might be harmful. We therefore ask-Is it impossible to look again at these cohorts?
30. Lim SM, Kim HJ, Nam M, Chung JH, Park YH. {{Association study of DISC1 in Korean population with autism spectrum disorders}}. {Psychiatr Genet};2009 (Jun);19(3):160.
31. Lind SE, Bowler DM. {{Language and theory of mind in autism spectrum disorder: the relationship between complement syntax and false belief task performance}}. {J Autism Dev Disord};2009 (Jun);39(6):929-937.
This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of « hacking out » solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a « memory for complements » task, a measure of receptive vocabulary, and traditional location change and unexpected contents false belief tasks. Consistent with predictions, the correlation between complement syntax score and location change task performance was significantly stronger within the ASD group than within the comparison group. However, contrary to predictions, complement syntax score was not significantly correlated with unexpected contents task performance within either group. Possible explanations for this pattern of results are considered.
32. Luong J, Yoder MK, Canham D. {{Southeast Asian parents raising a child with autism: a qualitative investigation of coping styles}}. {J Sch Nurs};2009 (Jun);25(3):222-229.
Autism is a developmental disability increasing in incidence over the past decade. Parents of children with autism experience prolonged levels of stress and isolation. Using qualitative research design, nine parents of children with autism participated in this study that focused on the effect of autism on the family, coping styles, and support systems. The target population was first-generation Southeast Asian American parents. Results revealed nine coping style patterns: (a) denial/passive coping, (b) empowerment, (c) redirecting energy, (d) shifting of focus, (e) rearranging life and relationships, (f) changed expectations, (g) social withdrawal, (h) spiritual coping, and (i) acceptance. The school was considered the primary supportive entity. Although findings may not be unique to the Southeast Asian group, the research provides an in-depth perspective on their lived experience, their struggles, and strengths. Insight gained from this investigation can help school nurses better understand the affect of autism on families, identify specific needs, and address these needs by advocating for appropriate supportive programs.
33. Magnee MJ, Oranje B, van Engeland H, Kahn RS, Kemner C. {{Cross-sensory gating in schizophrenia and autism spectrum disorder: EEG evidence for impaired brain connectivity?}} {Neuropsychologia};2009 (Jun);47(7):1728-1732.
Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental disorders that have extensively been associated with impairments in functional brain connectivity. Using a cross-sensory P50 suppression paradigm, this study investigated low-level audiovisual interactions on cortical EEG activation, which provides crucial information about functional integrity of connections between brain areas involved in cross-sensory processing in both disorders. Thirteen high functioning adult males with ASD, 13 high functioning adult males with schizophrenia, and 16 healthy adult males participated in the study. No differences in neither auditory nor cross-sensory P50 suppression were found between healthy controls and individuals with ASD. In schizophrenia, attenuated P50 responses to the first auditory stimulus indicated early auditory processing deficits. These results are in accordance with the notion that filtering deficits may be secondary to earlier sensory dysfunction. Also, atypical cross-sensory suppression was found, which implies that the cognitive impairments seen in schizophrenia may be due to deficits in the integrity of connections between brain areas involved in low-level cross-sensory processing.
34. Mantis JG, Fritz CL, Marsh J, Heinrichs SC, Seyfried TN. {{Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets}}. {Epilepsy Behav};2009 (Jun);15(2):133-141.
Rett syndrome (RTT) is a rare X-linked autistic-spectrum neurological disorder associated with impaired energy metabolism, seizure susceptibility, progressive social behavioral regression, and motor impairment primarily in young girls. The objective of this study was to examine the influence of restricted diets, including a ketogenic diet (KD) and a standard rodent chow diet (SD), on behavior in male Mecp2(308/y) mice, a model of RTT. The KD is a high-fat, low-carbohydrate diet that has anticonvulsant efficacy in children with intractable epilepsy and may be therapeutic in children with RTT. Following an 11-day pretrial period, adult wild-type and mutant Rett mice were separated into groups that were fed either an SD in unrestricted or restricted amounts or a ketogenic diet (KetoCal) in restricted amounts for a total of 30 days. The restricted diets were administered to reduce mouse body weight by 20-23% compared to the body weight of each mouse before the initiation of the diet. All mice were subjected to a battery of behavioral tests to determine the influence of the diet on the RTT phenotype. We found that performance in tests of motor behavior and anxiety was significantly worse in male RTT mice compared to wild-type mice and that restriction of either the KD or the SD improved motor behavior and reduced anxiety. We conclude that although both restricted diets increased the tendency of Rett mice to explore a novel environment, the beneficial effects of the KD were due more to calorie restriction than to the composition of the diet. Our findings suggest that calorically restricted diets could be effective in reducing the anxiety and in improving motor behavior in girls with RTT.
35. Marschik PB, Einspieler C, Oberle A, Laccone F, Prechtl HF. {{Case report: retracing atypical development: a preserved speech variant of Rett syndrome}}. {J Autism Dev Disord};2009 (Jun);39(6):958-961.
The subject of the present study is the development of a girl with the preserved speech variant of Rett disorder. Our data are based on detailed retrospective and prospective video analyses. Despite achieving developmental milestones, movement quality was already abnormal during the girl’s first half year of life. In addition, early hand stereotypies, idiosyncratic vocalizations, asymmetric eye opening, and abnormal facial expressions are early signs proving that this variant of the Rett complex, too, manifests itself within the first months of life.
36. Matson JL, Dempsey T, Fodstad JC. {{Stereotypies and repetitive/restrictive behaviours in infants with autism and pervasive developmental disorder}}. {Dev Neurorehabil};2009 (Jun);12(3):122-127.
PURPOSE: Autism Spectrum Disorders (ASD) are characterized by severe and debilitating symptoms including stereotyped and repetitive behaviours. Stereotypies and repetitive behaviours constitute core features of ASD and markedly impede attempts to remediate the disorder. Little previous research has examined characteristics of the core features of ASD in infants. METHOD: In the present study, 760 infants with autism, PDD-NOS or no diagnosis of ASD but at risk for other developmental delays or physical disabilities were evaluated with respect to the nature and extent of their stereotyped and ritualistic behaviour using the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). A Kruskal-Wallis test with follow-up Mann-Whitney tests were employed to test for significant differences. RESULTS: Infants with autism evinced the highest amount of stereotypic behaviour, followed by those with PDD-NOS and atypical development. A sub-set of BISCUIT items could accurately predict diagnostic group membership. CONCLUSIONS: These data suggest that many core features of ASD are distinct and can be reliably identified early in life. The potential early identification of these behavioural challenges could lead to earlier intervention practices and symptom alleviation for children in this population.
37. Mironov SL, Skorova E, Hartelt N, Mironova LA, Hasan MT, Kugler S. {{Remodelling of the respiratory network in a mouse model of Rett syndrome depends on brain-derived neurotrophic factor regulated slow calcium buffering}}. {J Physiol};2009 (Jun 1);587(Pt 11):2473-2485.
Rett syndrome caused by MeCP2 mutations is a devastating neurodevelopmental disorder accompanied by severe breathing irregularities. Using transduction of organotypic slices from model MeCP2-/y mice with neuron-specific calcium sensor protein D3cpv, we examined the slow calcium buffering in neurons in pre-Botzinger complex (preBotC), a component of the complex respiratory network. Examination of wild-type (WT) and MeCP2 null mice showed clear differences in the spatial organisations of neurons in preBotC and also in the disturbances in calcium homeostasis in mutant mice during early postnatal development. Deregulated calcium buffering in MeCP2-/y neurons was indicated by increased amplitude and kinetics of depolarisation-induced calcium transients. Both effects were related to an insufficient calcium uptake into the endoplasmic reticulum that was restored after pretreatment with brain-derived neurotrophic factor (BNDF). Conversely, the inhibition of BDNF signalling in WT neurons produced disturbances similar to those observed in MeCP2-/y mice. Brief hypoxia and calcium release from internal stores induced global calcium increases, after which the processes of many MeCP2-/y neurons were retracted, an effect that was also corrected by pretreatment with BDNF. The data obtained point to a tight connection between calcium homeostasis and long-term changes in neuronal connectivity. We therefore propose that calcium-dependent retraction of neurites in preBotC neurons can cause remodelling of the neuronal network during development and set up the conditions for appearance of breathing irregularities in Rett model mice.
38. Noor A, Gianakopoulos PJ, Fernandez B, Marshall CR, Szatmari P, Roberts W, Scherer SW, Vincent JB. {{Copy number variation analysis and sequencing of the X-linked mental retardation gene TSPAN7/TM4SF2 in patients with autism spectrum disorder}}. {Psychiatr Genet};2009 (Jun);19(3):154-155.
39. Olsen J, Zhu JL. {{Re: « Advanced parental age and the risk of autism spectrum disorder »}}. {Am J Epidemiol};2009 (Jun 1);169(11):1406; author reply 1406-1407.
40. Oosterling IJ, Swinkels SH, van der Gaag RJ, Visser JC, Dietz C, Buitelaar JK. {{Comparative analysis of three screening instruments for autism spectrum disorder in toddlers at high risk}}. {J Autism Dev Disord};2009 (Jun);39(6):897-909.
Several instruments have been developed to screen for autism spectrum disorders (ASD) in high-risk populations. However, few studies compare different instruments in one sample. Data were gathered from the Early Screening of Autistic Traits Questionnaire, Social Communication Questionnaire, Communication and Symbolic Behavior Scales-Developmental Profile, Infant-Toddler Checklist and key items of the Checklist for Autism in Toddlers in 238 children (mean age = 29.6 months, SD = 6.4) at risk for ASD. Discriminative properties are compared in the whole sample and in two age groups separately (8-24 months and 25-44 months). No instrument or individual item shows satisfying power in discriminating ASD from non-ASD, but pros and cons of instruments and items are discussed and directions for future research are proposed.
41. Paul R. {{Parents ask: Am i risking autism if i vaccinate my children?}} {J Autism Dev Disord};2009 (Jun);39(6):962-963.
42. Phelps KW, McCammon SL, Wuensch KL, Golden JA. {{Enrichment, stress, and growth from parenting an individual with an autism spectrum disorder}}. {J Intellect Dev Disabil};2009 (Jun);34(2):133-141.
BACKGROUND: Past researchers have focused primarily on the associated negative impact of caring for a child with special needs. In this study, caregivers report the enrichment and stress of caring for a child with an autism spectrum disorder. METHOD: Eighty caregivers completed the Social Communication Questionnaire (SCQ), Effects of the Situation Questionnaire (ESQ), and Posttraumatic Growth Inventory (PTGI). Enrichment and stress scores were compared to symptom severity data and posttraumatic growth scores. RESULTS: Consistent with prior research, caregivers reported greater levels of stress than enrichment. On just over half of the stress/enrichment variables, parental ratings of stress and enrichment were negatively correlated. Scores of total stress and enrichment were not correlated to the severity of the individual’s symptoms or caregivers’ growth scores. CONCLUSIONS: These findings suggest that although stress is a major concern for caregivers, enrichment and growth may also occur in varying degrees.
43. Raznahan A, Pugliese L, Barker GJ, Daly E, Powell J, Bolton PF, Murphy DG. {{Serotonin transporter genotype and neuroanatomy in autism spectrum disorders}}. {Psychiatr Genet};2009 (Jun);19(3):147-150.
There is increasing evidence that people with autism spectrum disorders (ASDs) have abnormalities in the serotonergic system. For example, a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR long/short polymorphism) has been reported to confer risk for ASDs, and to affect cortical grey matter volume in young children. However, the persistence of this association later in development is unknown. Hence, we investigated whether variation in the 5HTTLPR long/short polymorphism modulates brain anatomy in older people with ASD. We related 5HTTLPR long/short polymorphism in 43 adolescents and adults with ASD to brain anatomy using structural magnetic resonance imaging and voxel-based morphometry. There were no significant associations between brain anatomy and genotype. When considered alongside evidence of a relationship between 5HTTLPR genotype and brain volume amongst children with autism, our findings raise the possibility that the relationship between 5HTTLPR polymorphism and brain anatomy in ASDs anatomy may differ as a function of age and/or ASD subdiagnosis.
44. Rout UK, Clausen P. {{Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders}}. {Neurosci Res};2009 (Jun);64(2):162-169.
Autism spectrum disorder (ASD) is a disease of neuro-developmental origin of uncertain etiology. The current understanding is that both genetic and environmental factors contribute to the development of ASD. Exposure to valproate, thalidomide and alcohol during gestation are amongst the environmental triggers that are associated with the development of ASD. These teratogens may disturb the ontogeny of the brain by altering the expression pattern of genes that regulate the normal development of the brain. In this study, a neuron-like PC-12 cell model was used to examine the effects of these compounds on the binding potential of 50 different transcription factors to understand the molecular mechanism/s that may be involved in the teratogenesis caused by these agents. Cells in culture were treated with low or high concentrations of teratogens within a range that are reported in the blood of individuals. A pronounced increase in GATA transcription factor binding was observed for all three teratogens. Furthermore, Western blot analysis showed that GATA-3 level in the nuclear fractions was enhanced by each of the three teratogens. Results suggest that altered gene expression pattern due to heightened GATA-3 activities in the fetral brains following exposure to these teratogens may contribute to the development of ASD.
45. Schwartz CB, Henderson HA, Inge AP, Zahka NE, Coman DC, Kojkowski NM, Hileman CM, Mundy PC. {{Temperament as a predictor of symptomotology and adaptive functioning in adolescents with high-functioning autism}}. {J Autism Dev Disord};2009 (Jun);39(6):842-855.
Variation in temperament is characteristic of all people but is rarely studied as a predictor of individual differences among individuals with autism. Relative to a matched comparison sample, adolescents with High-Functioning Autism (HFA) reported lower levels of Surgency and higher levels of Negative Affectivity. Variability in temperament predicted symptomotology, social skills, and social-emotional outcomes differently for individuals with HFA than for the comparison sample. This study is unique in that temperament was measured by self-report, while all outcome measures were reported by parents. The broader implications of this study suggest that by identifying individual variability in constructs, such as temperament, that may influence adaptive functioning, interventions may be developed to target these constructs and increase the likelihood that individuals with HFA will achieve more adaptive life outcomes.
46. Seyfried TN, Heinecke KA, Mantis JG, Denny CA. {{Brain lipid analysis in mice with Rett syndrome}}. {Neurochem Res};2009 (Jun);34(6):1057-1065.
Rett syndrome (RS) is an X-linked neurodevelopmental disorder mostly involving mutations in the gene for methyl-CpG-binding protein 2 (MECP2). Ganglioside abnormalities were previously found in cerebrum and cerebellum in RS patients. We evaluated total lipid distribution in cerebrum/brainstem, hippocampus, and cerebellum in male mice carrying either the Mecp2 (tm1.1Bird) knockout mutation or the Mecp2 (308/y) deletion mutation. The concentration of the neuronal enriched ganglioside GD1a was significantly lower in the cerebrum/brainstem of Mecp2 (tm1.1Bird) mice than in that of age matched controls, but was not reduced in the Mecp2 (308/y) mice. No other differences in brain lipid content, including myelin-enriched cerebrosides, were detected in mice with either type of Mecp2 mutation. These findings indicate that the poor motor performance previously reported in the RS mutant mice is not associated with major brain lipid abnormalities and that most previous brain lipid abnormalities observed in RS patients were not observed in the Mecp2 (tm1.1Bird) or the Mecp2 (308/y) RS mice.
47. Shinawi M, Patel A, Panichkul P, Zascavage R, Peters SU, Scaglia F. {{The Xp contiguous deletion syndrome and autism}}. {Am J Med Genet A};2009 (Jun);149A(6):1138-1148.
Xp22 nullisomy in males causes a phenotype consistent with the loss of one or more of the genes located in this chromosomal region. Females with similar Xp deletions rarely manifest the same phenotype. Here we describe a 10-year-old girl with a de novo interstitial deletion encompassing Xp22.2p22.32 who presented with autism, moderate mental retardation, and some dysmorphic features. The deletion was delineated by FISH and STR analyses, and the breakpoints were determined using the Agilent 244 K oligonucleotide array. We found that the 5.5 Mb deletion is located on the paternal X chromosome and encompasses 18 genes. Further molecular and cytogenetic analyses showed unfavorable skewing of X-inactivation of the maternal (intact) chromosome. The phenotype of our patient was compared with previously reported female patients with deletions encompassing the same chromosomal region. We discuss the potential role of the genes in the deleted region and X chromosome inactivation in the pathogenesis of the phenotypic abnormalities seen in our patient. Our findings suggest that the severity and the variability of the clinical findings are determined by the size and the parental origin of the deletions as well as the X-inactivation status.
48. Sousa I, Clark TG, Toma C, Kobayashi K, Choma M, Holt R, Sykes NH, Lamb JA, Bailey AJ, Battaglia A, Maestrini E, Monaco AP. {{MET and autism susceptibility: family and case-control studies}}. {Eur J Hum Genet};2009 (Jun);17(6):749-758.International Molecular Genetic Study of Autism Consortium (IMGSAC)
Autism is a common, severe and highly heritable neurodevelopmental disorder. The International Molecular Genetic Study of Autism Consortium (IMGSAC) genome screen for linkage in affected sib-pair families identified a chromosome 7q susceptibility locus (AUTS1), that has subsequently shown evidence of increased sharing in several independent multiplex samples and in two meta-analyses. Taking into account the location of the MET gene under this linkage peak, and the fact that it has recently been reported to be associated with autism, the gene was further analyzed as a promising autism candidate. The gene encodes a transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter factor (HGF/SF). MET is best known as an oncogene, but its signalling also participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum (all of which have been observed earlier as being disregulated in individuals with autism). Here we present a family-based association analysis covering the entire MET locus. Significant results were obtained in both single locus and haplotype approaches with a single nucleotide polymorphism in intron 1 (rs38845, P<0.004) and with one intronic haplotype (AAGTG, P<0.009) in 325 multiplex IMGSAC families and 10 IMGSAC trios. Although these results failed to replicate in an independent sample of 82 Italian trios, the association itself was confirmed by a case-control analysis performed using the Italian cohort (P<0.02). The previously reported positive association of rs1858830 failed to replicate in this study. Overall, our findings provide further evidence that MET may play a role in autism susceptibility.
49. Spence SJ, Schneider MT. {{The role of epilepsy and epileptiform EEGs in autism spectrum disorders}}. {Pediatr Res};2009 (Jun);65(6):599-606.
Autism is a neurodevelopmental disorder of unknown etiology characterized by social and communication deficits and the presence of restricted interests/repetitive behaviors. Higher rates of epilepsy have long been reported, but prevalence estimates vary from as little as 5% to as much as 46%. This variation is probably the result of sample characteristics that increase epilepsy risk such as sample ascertainment, lower intelligence quotient (IQ), the inclusion of patients with nonidiopathic autism, age, and gender. However, critical review of the literature reveals that the rate in idiopathic cases with normal IQ is still significantly above the population risk suggesting that autism itself is associated with an increased risk of epilepsy. Recently, there has been interest in the occurrence of epileptiform electroencephalograms (EEGs) even in the absence of epilepsy. Rates as high as 60% have been reported and some investigators propose that these abnormalities may play a causal role in the autism phenotype. Although this phenomenon is still not well understood and risk factors have yet to be determined, the treatment implications are increasingly important. We review the recent literature to elucidate possible risk factors for both epilepsy and epileptiform EEGs. We then review existing data and discuss controversies surrounding treatment of EEG abnormalities.
50. Starling J, Dossetor D. {{Pervasive developmental disorders and psychosis}}. {Curr Psychiatry Rep};2009 (Jun);11(3):190-196.
Pervasive developmental disorders (PDDs) and infantile schizophrenia were initially thought to be the same condition, but distinct differences were described in later research. However, attempts to identify psychosis in individuals with PDDs continue to be challenging and controversial. The two disorders share many similar features, including perceptual abnormalities, thought disorder, catatonia, and deficiencies in reality testing. Progress has been made in describing features of PDDs that can be confused with psychosis and in surveying the prevalence of psychotic symptoms in populations with intellectual disability, although there are fewer data on PDD populations. Further research is needed on the longitudinal course of PDDs and the relationships with adult disorders such as psychosis and mood disorders. This research would not only improve the diagnosis and treatment of these complex disorders but would help to unravel the complex brain pathways involved in the perception of the external world that is central to psychosis and PDDs.
51. Stichter JP, Randolph JK, Kay D, Gage N. {{The use of structural analysis to develop antecedent-based interventions for students with autism}}. {J Autism Dev Disord};2009 (Jun);39(6):883-896.
Evidence continues to maintain that the use of antecedent variables (i.e., instructional practices, and environmental characteristics) increase prosocial and adaptive behaviors of students with disabilities (e.g., Kern et al. in J Appl Behav Anal 27(1):7-19, 1994; Stichter et al. in Behav Disord 30:401-418, 2005). This study extends the literature by systematically utilizing practitioner-implemented structural analyzes within school settings to determine antecedent variables affecting the prosocial behavior of students with autism. Optimal antecedents were combined into intervention packages and assessed utilizing a multiple baseline design across settings. All three students demonstrated improvement across all three settings. Rates of engagement and social interaction were obtained from classroom peers to serve as benchmark data. Findings indicate that practitioners can implement structural analyzes and design corresponding interventions for students with ASD within educational settings.
52. Tabares-Seisdedos R, Rubenstein JL. {{Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer}}. {Mol Psychiatry};2009 (Jun);14(6):563-589.
Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophr
