1. Al Anbar NN, Dardennes RM, Prado-Netto A, Kaye K, Contejean Y. {{Treatment choices in autism spectrum disorder: the role of parental illness perceptions}}. {Res Dev Disabil} (May-Jun);31(3):817-828.
A cross-sectional design was employed. Parents of a child with Autism Spectrum Disorder (ASD) were asked to complete a modified version of the Revised Illness-Perception Questionnaire (IPQ-RA) and answer questions about information-seeking activities and treatments used. Internal consistency, construct validity, and factor structure were assessed. Multivariate logistic regressions were performed. Eighty-nine parents having a child with ASD took part in the study. Five subscales of the IPQ-R were replicated. Causes were split into personal, external and hereditary factors. The most highly rated main cause was a genetic cause. Perception of seriousness of the disease was associated with the use of educative methods and unpredictable course of disorder associated with drug use. A higher sense of personal control was associated with reduced use of nutritional or pharmaceutical treatments. Attendance to training programs was associated with higher hereditary beliefs and lower perception of cyclical timeline. The IPQ-RA captures components of representations of autism and provides a reliable mean for exploring illness concept in parents of a child with ASD. Some illness dimensions may prevent parents from having the opportunity to modify their concept of autism. Such measure may be useful for assessing the modification of potentially malleable beliefs with psychoeducational interventions.
2. Anholt GE, Cath DC, van Oppen P, Eikelenboom M, Smit JH, van Megen H, van Balkom AJ. {{Autism and ADHD symptoms in patients with OCD: Are they associated with specific OC symptom dimensions or OC symptom severity?}}. {J Autism Dev Disord} (May);40(5):580-589.
In obsessive-compulsive disorder (OCD), the relationship between autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and obsessive-compulsive (OC) symptom dimensions and severity has scarcely been studied. Therefore, 109 adult outpatients with primary OCD were compared to 87 healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD and autism symptom frequencies, OCD + ADHD patients reporting more autism symptoms (particularly attention switching and social skills problems) than OCD – ADHD patients. Attention switching problems were most significant predictors of OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not associated with elevated autism scale scores, but with inattention. In conclusion, attention switching problems may reflect both symptom overlap and a common etiological factor underlying ASD, ADHD and OCD.
3. Bahi-Buisson N, Nectoux J, Girard B, Van Esch H, De Ravel T, Boddaert N, Plouin P, Rio M, Fichou Y, Chelly J, Bienvenu T. {{Revisiting the phenotype associated with FOXG1 mutations: two novel cases of congenital Rett variant}}. {Neurogenetics} (May);11(2):241-249.
The Forkhead box G1 (FOXG1) is a transcription factor that is critical for forebrain development, where it promotes progenitor proliferation and suppresses premature neurogenesis. Recently, the FOXG1 gene was implicated in the molecular aetiology of the congenital variant of Rett syndrome. So far, 15 FOXG1 molecular alterations, including only eight point mutations, have been reported. We screened the FOXG1 gene in a cohort of 206 MECP2 and CDKL5 mutation negative patients (136 females and 70 males) with severe encephalopathy and microcephaly. The screening was negative in all males, but two de novo mutations (c.1248C>G, p.Y416X and c.460_461dupG, p.E154GfsX300) were identified in two unrelated girls. Both patients showed neurological symptoms from the neonatal period with poor reactivity, hypotonia, and severe microcephaly. During the first year of life, both patients had feeding difficulties and made slow developmental progress. At 5 years old, the girls were significantly neurologically impaired with gross hypotonia, no language, convergent strabismus, and no voluntary hand use. Moreover, they presented a combination of jerky movements, hand-mouthing, and hand-washing stereotypies. Hence, FOXG1 mutation patients demonstrate severe encephalopathy compatible with the congenital variant, as well as additional features such as absent eye contact, inconsolable crying during the perinatal period, and delayed myelination with thin to hypoplastic corpus callosum. Although the overall frequency of mutations in FOXG1 in females with severe mental retardation and microcephaly appears to be low (1.5%), our findings suggest the requirement to investigate both point mutations and gene dosage in the FOXG1 gene in patients with severe encephalopathy with microcephaly and some Rett-like features.
4. Belinchon Carmona M, Boada Munoz L, Garcia de Andres E, Fuentes Biggi J, Posada de la Paz M. {{[Trends in studies on autism in Spain: Publications and authorship networks (1974-2007).]}}. {Psicothema} (May);22(2):242-249.
All the papers on autism published in journals by Spanish authors until 2007 were reviewed in order to identify changes and trends in studies, journals and authorship networks. A total of 567 works were analyzed. Results showed a continuous increase in the total number of publications and collaborative works (especially from 1999 onwards), as well as coincidence of the general framework of papers with the guidelines for research and treatment on autism that were published in the Anglo-Saxon arena for the same period. Some weak points were also identified, such as the low proportion of empirical and funded studies, low impact of the journals, and low author continuity, which have also been noted for other domains of research in Spain. We conclude that psychological and biomedical research on autism is currently a growing field in our country. However, important changes are needed, both in the way the authors conduct and communicate their studies, and in the commitment of some institutions (specially, universities and parent advocacy groups). Lastly, some proposals are suggested to improve the scientific quality of future studies and their usefulness for people with autism.
5. Bhaumik S, Tyrer F, Barrett M, Tin N, McGrother CW, Kiani R. {{The relationship between carers’ report of autistic traits and clinical diagnoses of autism spectrum disorders in adults with intellectual disability}}. {Res Dev Disabil} (May-Jun);31(3):705-712.
It is often difficult to determine the triad of impairments and whether autistic features are the consequence of intellectual impairment or autism spectrum disorders in people with intellectual disability (ID). The aim of the current study was to investigate the relationship between carer-reported autistic traits and independent diagnoses of autism spectrum disorders (ASD). Data were collected on carers’ subjective report of autistic traits and clinical diagnoses of ASD. Of 1145 adults with ID identified, 220 (19%) individuals had a diagnosis of ASD, and 778 (68%) individuals had at least one autistic trait. Optimal sensitivity and specificity were achieved with two or more autistic traits (sensitivity 63%; specificity 79%) and the positive predictive value increased substantially as the number of autistic traits increased. However, a significant proportion of individuals with ID who did not have a diagnosis of ASD also displayed autistic traits. Our findings suggest that in the absence of other measures, the presence of autistic traits can serve as a useful proxy measure for ASD in research (and/or clinical settings). However, although information on autistic traits may help healthcare practitioners to identify people with possible ASD, it cannot be used alone to make a formal diagnosis.
6. Bird G, Silani G, Brindley R, White S, Frith U, Singer T. {{Empathic brain responses in insula are modulated by levels of alexithymia but not autism}}. {Brain} (May);133(Pt 5):1515-1525.
Difficulties in social cognition are well recognized in individuals with autism spectrum conditions (henceforth ‘autism’). Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism, much less is known about the capacity of individuals with autism for affect sharing. Based on previous data suggesting that empathy deficits in autism are a function of interoceptive deficits related to alexithymia, we aimed to investigate empathic brain responses in autistic and control participants with high and low degrees of alexithymia. Using functional magnetic resonance imaging, we measured empathic brain responses with an ’empathy for pain’ paradigm assessing empathic brain responses in a real-life social setting that does not rely on attention to, or recognition of, facial affect cues. Confirming previous findings, empathic brain responses to the suffering of others were associated with increased activation in left anterior insula and the strength of this signal was predictive of the degree of alexithymia in both autistic and control groups but did not vary as a function of group. Importantly, there was no difference in the degree of empathy between autistic and control groups after accounting for alexithymia. These findings suggest that empathy deficits observed in autism may be due to the large comorbidity between alexithymic traits and autism, rather than representing a necessary feature of the social impairments in autism.
7. Brang D, Ramachandran VS. {{Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic dysregulation as the neural basis for autism}}. {Med Hypotheses} (May);74(5):919-921.
Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another’s viewpoint – a failure to construct a « theory of mind » for interpreting another person’s thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in « empathy » related mirror neurons (MNS) and projects (via the TOP junction – just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection.
8. Buizer-Voskamp JE, Franke L, Staal WG, van Daalen E, Kemner C, Ophoff RA, Vorstman JA, van Engeland H, Wijmenga C. {{Systematic genotype-phenotype analysis of autism susceptibility loci implicates additional symptoms to co-occur with autism}}. {Eur J Hum Genet} (May);18(5):588-595.
Many genetic studies in autism have been performed, resulting in the identification of multiple linkage regions and cytogenetic aberrations, but little unequivocal evidence for the involvement of specific genes exists. By identifying novel symptoms in these patients, enhanced phenotyping of autistic individuals not only improves understanding and diagnosis but also helps to define biologically more homogeneous groups of patients, improving the potential to detect causative genes. Supported by recent copy number variation findings in autism, we hypothesized that for some susceptibility loci, autism resembles a contiguous gene syndrome, caused by aberrations within multiple (contiguous) genes, which jointly increases autism susceptibility. This would result in various different clinical manifestations that might be rather atypical, but that also co-occur with autism. To test this hypothesis, 13 susceptibility loci, identified through genetic linkage and cytogenetic analyses, were systematically analyzed. The Online Mendelian Inheritance in Man database was used to identify syndromes caused by mutations in the genes residing in each of these loci. Subsequent analysis of the symptoms expressed within these disorders allowed us to identify 33 symptoms (significantly more than expected, P=0.037) that were over-represented in previous reports mapping to these loci. Some of these symptoms, including seizures and craniofacial abnormalities, support our hypothesis as they are already known to co-occur with autism. These symptoms, together with ones that have not previously been described to co-occur with autism, might be considered for use as inclusion or exclusion criteria toward defining etiologically more homogeneous groups for molecular genetic studies of autism.
9. Buoni S, Zannolli R, De Felice C, De Nicola A, Guerri V, Guerra B, Casali S, Pucci B, Corbini L, Mari F, Renieri A, Zappella M, Hayek J. {{EEG features and epilepsy in MECP2-mutated patients with the Zappella variant of Rett syndrome}}. {Clin Neurophysiol} (May);121(5):652-657.
OBJECTIVE: To assess the presence/absence of peculiar EEG features and epilepsy in MECP2-mutated Rett patients with the Zappella-Rett variant (Z-RTT) also known as preserved speech variant. METHODS: Retrospective analysis of 16 (age 19.4+/-8.4years; range 8-38years) MECP2 mutated Z-RTT cases, including 11 high or intermediate performance (HIP), and five low-performance (LP) patients was performed. Peculiar EEG features were analyzed as a function of the HIP or LP Z-RTT categories: (1) centro-temporal spikes, (2) multifocal EEG activity, (3) EEG encephalopathy (i.e. multifocal EEG activity associated with the presence of background slowing and diffuse slow activity), (4) spindles and K-complex. Furthermore, we assessed the occurrence of epilepsy. Correlations between electroclinical features and category of Z-RTT genotype (missense or truncation mutation) were also tested. RESULTS: The Z-RTT HIP group showed a very abnormal EEG (presence of centro-temporal spikes: p=0.004808), although the cases studied were not epileptogenic and did not develop encephalopathy. The LP group showed multifocal EEG activity (p=0.000229), EEG encephalopathy (p=0.000229) and epilepsy (p=0.299451). No significant differences between the prevalence of centro-temporal spikes, multifocal EEG activity, EEG encephalopathy, and epilepsy between the patients with the truncation or missense mutation were observed. CONCLUSIONS: EEG electrophysiological patterns and epileptogenic susceptibility differ in Z-RTT according to the level of performance (i.e. HIP or LP). SIGNIFICANCE: These results indicate that HIP and LP Z-RTT should be considered as distinct entities, not only on a clinical basis, but also as it concerns EEG features and epileptogenic susceptibility. These results could offer support in the practical management of patients and family counseling.
10. Cohen IL, Tsiouris JA, Flory MJ, Kim SY, Freedland R, Heaney G, Pettinger J, Ted Brown W. {{A large scale study of the psychometric characteristics of the IBR Modified Overt Aggression Scale: Findings and evidence for increased self-destructive behaviors in adult females with autism spectrum disorder}}. {J Autism Dev Disord} (May);40(5):599-609.
The psychometric characteristics of the IBR Modified Overt Aggression Scale were studied in over 2,000 people with Intellectual Disability (ID). Reliability ranged from good to excellent. Aggression toward others and objects was highest in the youngest adults, in those in the moderate to severe range of ID, and in those with an autism spectrum diagnosis. Self-injury was highest in those in the severe to profound range of ID and in those with autism, particularly the females. Females with autism were also more likely to make the most self-deprecating statements. Our data suggest that adult females with autism are a unique group and support the notion that mood and anxiety disorders play a role in self-destructive behaviors in this population.
11. Downs J, Geranton SM, Bebbington A, Jacoby P, Bahi-Buisson N, Ravine D, Leonard H. {{Linking MECP2 and pain sensitivity: the example of Rett syndrome}}. {Am J Med Genet A} (May);152A(5):1197-1205.
Recent animal studies suggest links between MeCP2 function and sensitivity to pain. This study investigated the nature and prevalence of atypical pain responses in Rett syndrome and their relationships with specific MECP2 mutations. Families enrolled in the Australian Rett Syndrome Database (ARSD) and InterRett database participated in this study. Cases with a known MECP2 pathogenic mutation, whose families had completed a questionnaire on registration and had answered questions on pain sensitivity were included (n = 646). Logistic regression was used to analyze relationships between the atypical pain responses and genotype. Descriptions of decreased pain sensitivity were content analyzed. The prevalence estimate of reporting an abnormal pain response was 75.2% and a decreased sensitivity to pain was 65.0% in the population-based ARSD. Families of ARSD and InterRett subjects with a C-terminal (OR 2.6; 95% CI 0.8-8.0), p.R168X (OR 2.1; 95% CI 0.7-6.1), or p.R306C (OR 2.7; 95% CI 0.8-9.6) mutation were more likely to report decreased sensitivity to pain. Parents and carers described decreased and delayed responses in situations judged likely to cause pain such as injections, falls, trauma, and burns. This study has provided the first precise estimate of the prevalence of abnormal sensitivity to pain in Rett syndrome but specific relationships with genotype are not yet clear. Clinical practice should include a low threshold for the clinical assessment of potential injuries in Rett syndrome.
12. Fatemi SH. {{Co-occurrence of neurodevelopmental genes in etiopathogenesis of autism and schizophrenia}}. {Schizophr Res} (May);118(1-3):303-304.
13. Fernell E, Gillberg C. {{Autism spectrum disorder diagnoses in Stockholm preschoolers}}. {Res Dev Disabil} (May-Jun);31(3):680-685.
The aims of this study were to estimate prevalence rates of children with autism spectrum disorder (ASD) diagnoses in a cohort of 6-year-old children with birth year 2002, referred to the Autism Centre for Young Children, serving the whole of Stockholm county and on the basis of the available data discuss clinical aspects of assessment, habilitation and follow-up. Records of 142 of a total of 147 (123 boys and 24 girls) identified children with ASD diagnoses were scrutinised with respect to type of diagnosis, cognitive level, other developmental disorders and medical/neurological disorders. The overall prevalence of such disorders was 6.2/1000 (95% confidence interval 5.2-7.2/1000). The rates of learning disability/mental retardation, developmental delay without a specified cognitive level and normal intelligence constituted about one third, respectively. AS and atypical autism tended to be diagnosed more often at age 5-6 years while AD with learning disability/mental retardation was more often diagnosed at age 3-4 years. The awareness of ASDs has resulted in increasing numbers of children being diagnosed at young ages. We conclude that it is important to take into account these children’s broader developmental profiles, need for repeated assessment of cognitive functions and follow-up over time and also the requirement for medical/neurological consideration and work-up.
14. Fernell E, Hedvall A, Norrelgen F, Eriksson M, Hoglund-Carlsson L, Barnevik-Olsson M, Svensson L, Holm A, Westerlund J, Gillberg C. {{Developmental profiles in preschool children with autism spectrum disorders referred for intervention}}. {Res Dev Disabil} (May-Jun);31(3):790-799.
The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of « classic » autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children’s medical characteristics also vary considerably and will be detailed in a further report.
15. Griffith GM, Hastings RP, Nash S, Hill C. {{Using matched groups to explore child behavior problems and maternal well-being in children with Down syndrome and autism}}. {J Autism Dev Disord} (May);40(5):610-619.
Mothers of children with Down syndrome, autism, and mixed etiology intellectual disabilities, matched on child age, gender, and communication skills (n = 19 in each group) completed measures of their child’s adaptive and problem behaviors, their own parenting stress, and positive perceptions of their child. Children with autism were rated as having more problem behaviors and lower levels of social competence than children with Down syndrome and mixed etiology intellectual disabilities. Mothers of children with autism scored lower on positive perceptions of their child, and higher on stress than the other two groups. After selecting closely matched groups, we found several group differences in child behavior but little evidence of group differences in maternal outcomes.
16. Hadjikhani N. {{Serotonin, pregnancy and increased autism prevalence: is there a link?}}. {Med Hypotheses} (May);74(5):880-883.
The prevalence of autism, a neurodevelopmental condition resulting from genetic and environmental causes, has increased dramatically during the last decade. Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo-pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation. Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD. Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. In this paper, we hypothesize that increased serotonemia during pregnancy, including due to SSRI intake, could be one of the causes of the raising prevalence in autism. If our hypothesis is confirmed, it will not only shed light on one of the possible reason for autism prevalence, but also offer new preventive and treatment options.
17. Hagberg KW, Jick H. {{Autism in the UK for birth cohorts 1988-2001}}. {Epidemiology} (May);21(3):426-427.
18. Hilton CL, Fitzgerald RT, Jackson KM, Maxim RA, Bosworth CC, Shattuck PT, Geschwind DH, Constantino JN. {{Brief report: under-representation of african americans in autism genetic research: a rationale for inclusion of subjects representing diverse family structures}}. {J Autism Dev Disord} (May);40(5):633-639.
African American children with autism are seriously under-represented in existing genetic registries and biomedical research studies of autism. We estimated the number of African American children with autism in the St. Louis region using CDC surveillance data and present the outcomes of a concerted effort to enroll approximately one-third of that population into either of two large national genetic autism registries. The results revealed that even after traditional barriers to research participation were addressed and all contacted families expressed a willingness to participate, 67% of the reachable families were disqualified from participation because of family structure alone. Comprehensive efforts-including expansion of eligibility to families of diverse structure-are warranted to facilitate the inclusion of African American children in biomedical research.
19. Hitoglou M, Ververi A, Antoniadis A, Zafeiriou DI. {{Childhood autism and auditory system abnormalities}}. {Pediatr Neurol} (May);42(5):309-314.
Hearing disorders are common among children with autism, ranging from peripheral and sensorineural hearing deficit or loss to auditory hypersensitivity with bizarre reactions to sounds. The auditory abnormalities and consequent sensory deprivation exacerbate the communication deficit of autism, and early auditory assessment holds an important place in the planning of intervention and the overall prognosis of patients. Physiologic, pathologic, imaging, and neurochemical studies have revealed an array of aberrations in the perception and processing of the audiologic stimuli, including (among others) maturational defects, atypical lateralization, and serotonin dysfunction.
20. Hogart A, Wu D, LaSalle JM, Schanen NC. {{The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13}}. {Neurobiol Dis} (May);38(2):181-191.
A cluster of low copy repeats on the proximal long arm of chromosome 15 mediates various forms of stereotyped deletions and duplication events that cause a group of neurodevelopmental disorders that are associated with autism or autism spectrum disorders (ASD). The region is subject to genomic imprinting and the behavioral phenotypes associated with the chromosome 15q11.2-q13 disorders show a parent-of-origin specific effect that suggests that an increased copy number of maternally derived alleles contributes to autism susceptibility. Notably, nonimprinted, biallelically expressed genes within the interval also have been shown to be misexpressed in brains of patients with chromosome 15q11.2-q13 genomic disorders, indicating that they also likely play a role in the phenotypic outcome. This review provides an overview of the phenotypes of these disorders and their relationships with ASD and outlines the regional genes that may contribute to the autism susceptibility imparted by copy number variation of the region.
21. Ingersoll B. {{Broader autism phenotype and nonverbal sensitivity: evidence for an association in the general population}}. {J Autism Dev Disord} (May);40(5):590-598.
This study examined the relationship between characteristics of the Broader Autism Phenotype (BAP) and nonverbal sensitivity, the ability to interpret nonverbal aspects of communication, in a non-clinical sample of college students. One hundred and two participants completed a self-report measure of the BAP, the Autism Spectrum Quotient (AQ), and two tests of nonverbal sensitivity, the Test of Nonverbal Cue Knowledge (TONCK), and the Diagnostic Analysis of Nonverbal Accuracy 2 (DANVA2). AQ score was correlated with TONCK performance and number of errors on the adult faces subtest of the DANVA2, but not adult paralanguage or postures. These findings suggest that characteristics of ASD in the general population are associated with differences in both explicit and implicit knowledge of nonverbal cues.
22. Kosaka H, Omori M, Munesue T, Ishitobi M, Matsumura Y, Takahashi T, Narita K, Murata T, Saito DN, Uchiyama H, Morita T, Kikuchi M, Mizukami K, Okazawa H, Sadato N, Wada Y. {{Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders}}. {Neuroimage} (May 1);50(4):1357-1363.
Enlarged head circumference and increased brain weight have been reported in infants with pervasive developmental disorders (PDD), and volumetric studies suggest that children with PDD have abnormally enlarged brain volumes. However, little is known about brain volume abnormalities in young adults with PDD. We explored gray matter (GM) volume in young adults with PDD. T1-weighted volumetric images were acquired with a 3-T magnetic resonance scanner from 32 males with high-functioning PDD (23.8+/-4.2 years; Full Scale Intelligence Quotient [FSIQ]=101.6+/-15.6) and 40 age-matched normal male control subjects (22.5+/-4.3 years; FSIQ=109.7+/-7.9). Regional GM volumes were compared between the two groups using voxel-based morphometry (VBM) with the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). Compared with the control group, the high-functioning PDD group showed significantly less GM in the right insula, the right inferior frontal gyrus, and the right inferior parietal lobule. A conservative threshold confirmed considerably smaller volumes in the right insula and inferior frontal gyrus. In these areas, negative correlations were found between Autism Spectrum Quotient scores and GM volume, although no significant correlations were found between each subject’s FSIQ and GM volume. No regions showed greater GM volumes in the high-functioning PDD group. The insular cortex, which works as a relay area for multiple neurocognitive systems, may be one of the key regions underlying the complex clinical features of PDD. These smaller GM volumes in high-functioning PDD subjects may reflect the clinical features of PDD itself, rather than FSIQ.
23. Levy SE, Giarelli E, Lee LC, Schieve LA, Kirby RS, Cunniff C, Nicholas J, Reaven J, Rice CE. {{Autism Spectrum Disorder and Co-occurring Developmental, Psychiatric, and Medical Conditions Among Children in Multiple Populations of the United States}}. {J Dev Behav Pediatr} (Apr 24)
BACKGROUND:: Autism spectrum disorders (ASDs) often co-occur with other developmental, psychiatric, neurologic, or medical diagnoses. OBJECTIVE:: This study examined co-occurring non-ASD diagnoses and symptoms in a population-based cohort of 8 year olds identified with ASD. METHOD:: Data on 2,568 children meeting surveillance case definition for ASD were collected by a multi-site surveillance program. Information was systematically abstracted and reviewed from existing health and education source records and systematically entered into a summary record in a secure database. RESULTS:: Eighty-one percent of study children were male; 63% white, 23% black, 14% Hispanic, Asian, or not stated. When age of ASD classification was available, 20% were classified before age 3 years, 36% between ages 3 and 5 years, and 44% after age 5 years. The co-occurrence of >/=1 non-ASD developmental diagnoses was 83%, >/=1 psychiatric diagnoses was 10%, >/=1 neurologic diagnoses was 16%, and at least one possibly causative genetic or neurologic diagnosis was 4%. Children with a previous ASD classification and co-occurring psychiatric or neurologic conditions were more likely to be diagnosed or classified at a later age. Each category of co-occurring non-ASD diagnosis was significantly increased in children whose records did not include an ASD diagnosis or educational classification but who met surveillance criteria for ASD. CONCLUSIONS:: These data highlight the need for clinicians to keep in mind the high prevalence of associated diagnoses with an ASD diagnosis, and the possibility that in younger children other symptoms or disorders may be masking or obscuring core symptoms of ASD, which would lead to a diagnosis.
24. Loucas T, Riches NG, Charman T, Pickles A, Simonoff E, Chandler S, Baird G. {{Speech perception and phonological short-term memory capacity in language impairment: preliminary evidence from adolescents with specific language impairment (SLI) and autism spectrum disorders (ASD)}}. {Int J Lang Commun Disord} (May);45(3):275-286.
BACKGROUND: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. AIMS: This study aimed to investigate the contributions of PSTM and speech perception in non-word processing and whether individuals with SLI and ASD plus language impairment (ALI) show similar or different patterns of deficit in these cognitive processes. METHOD & PROCEDURES: Three groups of adolescents (aged 14-17 years), 14 with SLI, 16 with ALI, and 17 age and non-verbal IQ matched typically developing (TD) controls, made speeded discriminations between non-word pairs. Stimuli varied in PSTM load (two- or four-syllables) and speech perception load (mismatches on a word-initial or word-medial segment). OUTCOMES & RESULTS: Reaction times showed effects of both non-word length and mismatch position and these factors interacted: four-syllable and word-initial mismatch stimuli resulted in the slowest decisions. Individuals with language impairment showed the same pattern of performance as those with typical development in the reaction time data. A marginal interaction between group and item length was driven by the SLI and ALI groups being less accurate with long items than short ones, a difference not found in the TD group. CONCLUSIONS & IMPLICATIONS: Non-word discrimination suggests that there are similarities and differences between adolescents with SLI and ALI and their TD peers. Reaction times appear to be affected by increasing PSTM and speech perception loads in a similar way. However, there was some, albeit weaker, evidence that adolescents with SLI and ALI are less accurate than TD individuals, with both showing an effect of PSTM load. This may indicate, at some level, the processing substrate supporting both PSTM and speech perception is intact in adolescents with SLI and ALI, but also in both there may be impaired access to PSTM resources.
25. Mann JR, McDermott S, Bao H, Hardin J, Gregg A. {{Pre-eclampsia, birth weight, and autism spectrum disorders}}. {J Autism Dev Disord} (May);40(5):548-554.
Autism spectrum disorders (ASD) are primarily inherited, but perinatal or other environmental factors may also be important. In an analysis of 87,677 births from 1996 through 2002, insured by the South Carolina Medicaid program, birth weight was significantly inversely associated with the odds of ASD (OR = 0.78, p = .001 for each additional kilogram). Maternal pre-eclampsia/eclampsia was significantly associated with greater odds of ASD (OR = 1.85, p < .0001 without controlling for birth weight; OR = 1.69, p = .0005, when controlling for birth weight). We conclude that reduced birth weight partially mediates the association between pre-eclampsia/eclampsia and ASD. Additional research is needed to investigate the potential mechanism(s) by which pre-eclampsia/eclampsia may influence ASD risk.
26. Manning MM, Wainwright LD. {{The role of high level play as a predictor social functioning in autism}}. {J Autism Dev Disord} (May);40(5):523-533.
Play and social abilities of a group of children diagnosed with high functioning autism were compared to a second group diagnosed with a variety of developmental language disorders (DLD). The children with autism engaged in fewer acts of high level play. The children with autism also had significantly lower social functioning than the DLD group early in the play session; however, these differences were no longer apparent by the end of the play session. In addition, a significant association existed between play and social functioning regardless of diagnosis. This suggests that play may act as a current indicator of social ability while providing an arena for social skills practice.
27. Martin JS, Poirier M, Bowler DM. {{Brief report: impaired temporal reproduction performance in adults with autism spectrum disorder}}. {J Autism Dev Disord} (May);40(5):640-646.
Although temporal processing has received little attention in the autism literature, there are a number of reasons to suspect that people with autism spectrum disorder (ASD) may have particular difficulties judging the passage of time. The present study tested a group of 20 high-functioning adults with ASD and 20 matched comparison participants on a temporal reproduction task. The ASD group made reproductions that were significantly further from the base durations than did the comparison group. They were also more variable in their responses. Furthermore the ASD group showed particular difficulties as the base durations increased, tending to underestimate to a much greater degree than the comparison group. These findings support earlier evidence that temporal processing is impaired in ASD.
28. Marui T, Funatogawa I, Koishi S, Yamamoto K, Matsumoto H, Hashimoto O, Jinde S, Nishida H, Sugiyama T, Kasai K, Watanabe K, Kano Y, Kato N. {{Association between autism and variants in the wingless-type MMTV integration site family member 2 ( WNT2) gene}}. {Int J Neuropsychopharmacol} (May);13(4):443-449.
Autism is a severe neurodevelopmental disorder with a complex genetic aetiology. The wingless-type MMTV integration site family member 2 (WNT2) gene has been considered as a candidate gene for autism. We conducted a case-control study and followed up with a transmission disequilibrium test (TDT) analysis to confirm replication of the significant results for the first time. We conducted a case-control study of nine single nucleotide polymorphisms (SNPs) within the WNT2 gene in 170 patients with autism and 214 normal controls in a Japanese population. We then conducted a TDT analysis in 98 autistic families (trios) to replicate the results of the case-control study. In the case-control study, three SNPs (rs3779547, rs4727847 and rs3729629), two major individual haplotypes (A-T-C and G-G-G, consisting of rs3779547, rs4727847, and rs3729629), and global probability values of the haplotype distributions in the same region (global p=0.0091) showed significant associations with autism. Furthermore, all of these significant associations were also observed in the TDT analysis. Our findings provide evidence for a significant association between WNT2 and autism. Considering the important role of the WNT2 gene in brain development, our results therefore indicate that the WNT2 gene is one of the strong candidate genes for autism.
29. Mazumdar S, King M, Liu KY, Zerubavel N, Bearman P. {{The spatial structure of autism in California, 1993-2001}}. {Health Place} (May);16(3):539-546.
This article identifies significant high-risk clusters of autism based on residence at birth in California for children born from 1993 to 2001. These clusters are geographically stable. Children born in a primary cluster are at four times greater risk for autism than children living in other parts of the state. This is comparable to the difference between males and females and twice the risk estimated for maternal age over 40. In every year roughly 3% of the new caseload of autism in California arises from the primary cluster we identify-a small zone 20 km by 50 km. We identify a set of secondary clusters that support the existence of the primary clusters. The identification of robust spatial clusters indicates that autism does not arise from a global treatment and indicates that important drivers of increased autism prevalence are located at the local level.
30. Meguid N, Fahim C, Yoon U, Nashaat NH, Ibrahim AS, Mancini-Marie A, Brandner C, Evans AC. {{Brain morphology in autism and fragile X syndrome correlates with social IQ: first report from the Canadian-Swiss-Egyptian Neurodevelopmental Study}}. {J Child Neurol} (May);25(5):599-608.
Fragile X syndrome shares most of the behavioral phenotypic similarities with autism. How are these similarities reflected in brain morphology? A total of 10 children with autism and 7 with fragile X underwent morphological (T1) 1.5-T magnetic resonance imaging (MRI). The authors found no significant difference in total brain volumes, regional volumes, gyrification index, sulcul depth, and cerebral cortical thickness. However, children with autism showed significant decrease in the medial prefrontal bilaterally and the left anterior cingulate cortices. Regression analysis revealed positive correlation between the medial prefrontal cortical thickness and the social IQ. The authors suggest that the difference between the 2 groups in the medial prefrontal and anterior cingulate cortices thickness may entail an altered social cognitive style. Functional MRI studies directly differentiating between social indifference (autism) and social avoidance (fragile X) are needed to further characterize the spectrum of social abnormalities between these 2 groups.
31. Pillion JP, Bibat G, Naidu S. {{Effects of sedation on auditory brainstem response in Rett syndrome}}. {Pediatr Neurol} (May);42(5):331-334.
Prolongation of the I-V interpeak latency intervals have been reported in Rett syndrome and other neurodevelopmental disorders. It has been suggested that the use of sedation may account for differences in the interpeak latency intervals when comparisons are made across diagnostic groups if sedated control groups are not used for the basis of comparison. This study examined the effects of sedation on auditory brainstem response interpeak latency intervals (i.e., I-III, III-V, and I-V) in two groups: (1) a group with Rett syndrome who were positive for mutations in the MECP2 gene and (2) a group negative for mutations in the MECP2 gene but who were severely to profoundly delayed with other causes of mental retardation. To further assess the effects of sedation, a third group of sedated and nonsedated female participants, taken from an in-house normative auditory brainstem response database was also included. An analysis of variance indicated (1) longer I-V interpeak latency intervals in the sedated participants with Rett syndrome; (2) longer III-V interpeak latency intervals in the mutation-positive participants as compared to non-Rett syndrome, mutation-negative participants; and (3) no significant effects of sedation on the I-III, III-V, or I-V interpeak latency intervals among the normative group participants, according to t tests. The findings suggest a possible biological basis for the discrepancy in the literature on auditory brain stem responses in Rett syndrome, and warrant cautious interpretation of auditory brainstem responses findings in sedated subjects with Rett syndrome, as well as in those with mental retardation and seizures.
32. Ratzan SC. {{Setting the record straight: vaccines, autism, and the Lancet}}. {J Health Commun} (Apr);15(3):237-239.
33. Reichenberg A, Gross R, Sandin S, Susser ES. {{Advancing paternal and maternal age are both important for autism risk}}. {Am J Public Health} (May);100(5):772-773; author reply 773.
34. Sawyer MG, Bittman M, La Greca AM, Crettenden AD, Harchak TF, Martin J. {{Time demands of caring for children with autism: What are the implications for maternal mental health?}}. {J Autism Dev Disord} (May);40(5):620-628.
This study examined the relationship between maternal mental health problems and both caregiving time and experience of time pressure for 216 mothers of children with autism. Data describing caregiving time was obtained using 24-h time-diaries. Standard questionnaires were used to assess time pressure, social support, children’s emotional and behavioural problems, and maternal mental health problems. After adjusting for the effect of children’s age, maternal social support, and children’s behaviour problems, time pressure but not hours of caregiving, had a significant positive relationship with maternal mental health problems. Findings suggest that the quality of home-based care for children with autism may be adversely affected if time pressure experienced by caregivers compromises their mental health and well being.
35. Senju A, Southgate V, Miura Y, Matsui T, Hasegawa T, Tojo Y, Osanai H, Csibra G. {{Absence of spontaneous action anticipation by false belief attribution in children with autism spectrum disorder}}. {Dev Psychopathol} (May);22(2):353-360.
Recently, a series of studies demonstrated false belief understanding in young children through completely nonverbal measures. These studies have revealed that children younger than 3 years of age, who consistently fail the standard verbal false belief test, can anticipate others’ actions based on their attributed false beliefs. The current study examined whether children with autism spectrum disorder (ASD), who are known to have difficulties in the verbal false belief test, may also show such action anticipation in a nonverbal false belief test. We presented video stimuli of an actor watching an object being hidden in a box. The object was then displaced while the actor was looking away. We recorded children’s eye movements and coded whether they spontaneously anticipated the actor’s subsequent behavior, which could only have been predicted if they had attributed a false belief to her. Although typically developing children correctly anticipated the action, children with ASD failed to show such action anticipation. The results suggest that children with ASD have an impairment in false belief attribution, which is independent of their verbal ability.
36. Smith KR, Matson JL. {{Psychopathology: differences among adults with intellectually disabled, comorbid autism spectrum disorders and epilepsy}}. {Res Dev Disabil} (May-Jun);31(3):743-749.
The goal of this study was to systematically examine group differences among adults with intellectual disabilities (ID), comorbid autism spectrum disorders (ASD), and epilepsy through a detailed exploration of the characteristics that these disorders present in the area of psychopathology. Previous studies indicating that individuals with ID have comorbid ASD and epilepsy tend to stop short of addressing these disorders’ impact on the full range of psychosocial issues, particularly in adult samples. Assessment of psychopathology was made with the ASD-comorbidity-adult version (ASD-CA). One hundred participants, with ID held constant, were matched and compared across four equal groups comprising 25 participants with ID, 25 participants with epilepsy, 25 participants with ASD, and 25 participants with combined ASD and epilepsy. When controlling for age, gender, race, level of ID, and hearing and visual impairments, results of the MANOVA revealed significant differences among groups, Wilks’s Lambda=.76, F(15, 254)=1.82, p<.05, eta(2)=.09. A one-way ANOVA was conducted for each of the five subscales of the ASD-CA as follow-up tests to the MANOVA. Groups differed significantly Anxiety/Repetitive Behavior subscale, F(3, 96)=2.93, p<.05, eta(2)=.08, Irritability/Behavior excess subscale, F(3, 96)=4.74, p<.01, eta(2)=.13, Attention/Hyperactivity subscale, F(3, 96)=5.18, p<.01, eta(2)=.14, and Depressive Symptoms subscale, F(3, 96)=3.73, p<.01, eta(2)=.10. Trend analysis demonstrated that individuals with ID expressing combined comorbid ASD and epilepsy were significantly more impaired than the control group (ID only) or groups containing only a single comorbid factor with ID (ASD or epilepsy only). Implications of these findings elucidate the nature of these disorders and their influence on patient care and management.
37. Sugie Y, Sugie H, Fukuda T, Osawa J. {{Study of HOXD genes in autism particularly regarding the ratio of second to fourth digit length}}. {Brain Dev} (May);32(5):356-361.
Multiple genes are involved in the pathogenesis of autism. To study the causative gene, the relationship between autism endophenotypes and their closely related genes has been analyzed. There is a subgroup of autism spectrum disorder (ASD) in which the ratio of second digit length to fourth digit length (2D/4D) is low (short digit group, SDG). We studied the relationship between ASD and HOXD genes, which are located in the candidate locus for ASD and are associated with digit morphogenesis, with a particular focus on SDG. We analyzed 25 SNPs of HOXD11, HOXD12, and HOXD13 in the subject of 98 ASD, 89 healthy controls, and 16 non-autistic patients (non-ASD). There was no significant difference in the genotype frequencies between the ASD and the healthy controls. However, the G-112T heterozygote in the promoter region of HOXD11 was observed in only four patients with ASD and in none of the healthy controls or non-ASD subjects. Moreover, this HOXD11 G-112T was observed in three of 11 SDG with ASD but in none of the 15 non-SDG patients with ASD. There were eight SDG patients among the non-ASD ones, but this polymorphism was observed in none of them. Considering the above results, it is expected that candidate genes will be further identified, using HOXD11 G-112T polymorphism as a marker, by analyzing genes located near 2q in a larger number of ASD subjects with clinical signs of SDG.
38. Suzuki K, Nishimura K, Sugihara G, Nakamura K, Tsuchiya KJ, Matsumoto K, Takebayashi K, Isoda H, Sakahara H, Sugiyama T, Tsujii M, Takei N, Mori N. {{Metabolite alterations in the hippocampus of high-functioning adult subjects with autism}}. {Int J Neuropsychopharmacol} (May);13(4):529-534.
The aim of the present study was to investigate metabolite alterations in the hippocampal formation as they relate to aggression in high-functioning adults with autism. We measured concentrations of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr+PCr) in the hippocampal formation by proton magnetic resonance spectroscopy in 12 non-medicated male subjects with autism and 12 age- and sex-matched controls. Aggression was scored in the autistic subjects using the Buss-Perry Aggression Questionnaire. The concentrations of Cho and Cr+PCr in the hippocampal formation in autistic subjects were significantly higher than the corresponding values in control subjects, and a significant positive correlation was observed between the concentrations of these metabolites in the hippocampal formation and scores on the Buss-Perry Aggression Questionnaire in autistic subjects. Results suggest that high-functioning adult subjects with autism have abnormal metabolite concentrations in the hippocampal formation, which may in part account for their aggression.
39. Vazna A, Musova Z, Vlckova M, Novotna D, Dvorakova L, Hrdlicka M, Havlovicova M, Sedlacek Z. {{FMR1 gene expansion, large deletion of Xp, and skewed X-inactivation in a girl with mental retardation and autism}}. {Am J Med Genet A} (May);152A(5):1273-1277.
We describe a girl with mild facial anomalies, mild mental retardation, and atypical autism with a remarkable behavioral phenotype of persistent anger, aggression, and dysphoria. The occurrence of late-onset tremor and premature ovarian failure in the maternal branch of the family pointed to a possible defect in the FMR1 gene. Indeed, the patient carried a full FMR1 mutation. Unexpectedly, both alleles of the gene were almost completely methylated. Cytogenetic examination of the patient revealed in addition a large de novo deletion in band Xp22 on one of her X chromosomes. The deletion was fine mapped using oligonucleotide array CGH, and its breakpoints were localized using sequencing. The size of the deletion was about 17.4 Mb, and it contained more than 90 protein-coding genes. Microsatellite analysis indicated paternal origin of the aberrant chromosome. The large rearrangement was the most probable cause of the X-inactivation skewing, thus explaining the methylation of not only the expanded (maternal) but also the normal (paternal) FMR1 alleles. This pattern of skewed X-inactivation was confirmed using the analysis of methylation at the AR locus. The relatively mild phenotype of the patient resulted most likely from unmasking of the FMR1 defect. Although the deleted region contained many important genes, the phenotypic contribution of the rearranged X chromosome was probably limited by its almost complete inactivation. However, reduced dose of several genes escaping X-inactivation might also play a role in the phenotype of the patient.
40. Warren SF, Gilkerson J, Richards JA, Oller DK, Xu D, Yapanel U, Gray S. {{What automated vocal analysis reveals about the vocal production and language learning environment of young children with autism}}. {J Autism Dev Disord} (May);40(5):555-569.
The study compared the vocal production and language learning environments of 26 young children with autism spectrum disorder (ASD) to 78 typically developing children using measures derived from automated vocal analysis. A digital language processor and audio-processing algorithms measured the amount of adult words to children and the amount of vocalizations they produced during 12-h recording periods in their natural environments. The results indicated significant differences between typically developing children and children with ASD in the characteristics of conversations, the number of conversational turns, and in child vocalizations that correlated with parent measures of various child characteristics. Automated measurement of the language learning environment of young children with ASD reveals important differences from the environments experienced by typically developing children.
41. Webb SJ, Jones EJ, Merkle K, Namkung J, Toth K, Greenson J, Murias M, Dawson G. {{Toddlers with elevated autism symptoms show slowed habituation to faces}}. {Child Neuropsychol} (May);16(3):255-278.
We explored social information processing and its relation to social and communicative symptoms in toddlers with Autism Spectrum Disorder (ASD) and their siblings. Toddlers with more severe symptoms of autism showed slower habituation to faces than comparison groups; slower face learning correlated with poorer social skills and lower verbal ability. Unaffected toddlers who were siblings of children with ASD also showed slower habituation to faces compared with toddlers without siblings with ASD. We conclude that slower rates of face learning may be an endophenotype of ASD and is associated with more severe symptoms among affected individuals.
42. Wood L, Shepherd GM. {{Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in a mutant mouse model of Rett syndrome}}. {Neurobiol Dis} (May);38(2):281-287.
Motor and cognitive functions are severely impaired in Rett syndrome (RTT). Here, we examined local synaptic circuits of layer 2/3 (L2/3) pyramidal neurons in motor-frontal cortex of male hemizygous MeCP2-null mice at 3 to 4weeks of age. We mapped local excitatory input to L2/3 neurons using glutamate uncaging and laser scanning photostimulation, and compared synaptic input maps recorded from MeCP2-null and wild type (WT) mice. Local excitatory input was significantly reduced in the mutants. The strongest phenotype was observed for lateral (horizontal, intralaminar) inputs, that is, L2/3–>2/3 inputs, which showed a large reduction in MeCP2(-/y) animals. Neither the amount of local inhibitory input to these L2/3 pyramidal neurons nor their intrinsic electrophysiological properties differed by genotype. Our findings provide further evidence that excitatory networks are selectively reduced in RTT. We discuss our findings in the context of recently published parallel studies using selective MeCP2 knockdown in individual L2/3 neurons.
43. Zahorakova D, Jachymova M, Kemlink D, Baxova A, Martasek P. {{APOE epsilon4: a potential modulation factor in Rett syndrome}}. {J Child Neurol} (May);25(5):546-550.
Rett syndrome is a neurodevelopmental disorder mainly caused by de novo mutations in the MECP2 (methyl-CpG-binding protein 2) gene. There is considerable variation in the severity of clinical features among Rett syndrome patients, even among patients with the same MECP2 mutation. In addition to X-chromosome inactivation pattern, the genetic background of the affected individual might also have a role in determining the severity of the disorder. We suggest that APOE is one of the genetic modulating factors. We analyzed clinical phenotypes of 46 patients with Rett syndrome, with confirmed MECP2 mutation. We discovered that among epsilon4 carriers, some clinical features were more severe, and the developmental regression occurred 4 months earlier on average than in those without the epsilon4 allele. Earlier onset of regression suggests a possible trend; however, it did not achieve distinctive statistical significance. Nevertheless, the epsilon4 allele of APOE may serve as a candidate modulation factor for the Rett syndrome phenotype.
44. Zinke K, Fries E, Altgassen M, Kirschbaum C, Dettenborn L, Kliegel M. {{Visuospatial short-term memory explains deficits in tower task planning in high-functioning children with autism spectrum disorder}}. {Child Neuropsychol} (May);16(3):229-241.
Previous findings on planning abilities in individuals with high-functioning autism spectrum disorder (HFA) are inconsistent. Exploring possible reasons for these mixed findings, the current study investigated the involvement of memory in planning performance in 15 children with HFA and 17 typically developing controls. In addition to planning abilities (measured with the Tower of London), short-term memory and delayed recall for verbal as well as visuospatial material were assessed. Findings suggest that particularly reduced efficiency in visuospatial short-term memory is associated with Tower task planning deficits in children with HFA.
