Autistic symptomatology and language ability in autism spectrum disorder and specific language impairment

Background: Autism spectrum disorders (ASD) and specific language impairment (SLI) are common developmental disorders characterised by deficits in language and communication. The nature of the relationship between them continues to be a matter of debate. This study investigates whether the co-occurrence of ASD and language impairment is associated with differences in severity or pattern of autistic symptomatology or language profile. Methods: Participants (N = 97) were drawn from a total population cohort of 56,946 screened as part of study to ascertain the prevalence of ASD, aged 9 to 14 years. All children received an ICD-10 clinical diagnosis of ASD or No ASD. Children with nonverbal IQ 80 were divided into those with a language impairment (language score of 77 or less) and those without, creating three groups: children with ASD and a language impairment (ALI; N = 41), those with ASD and but no language impairment (ANL; N = 31) and those with language impairment but no ASD (SLI; N = 25). Results: Children with ALI did not show more current autistic symptoms than those with ANL. Children with SLI were well below the threshold for ASD. Their social adaptation was higher than the ASD groups, but still nearly 2 SD below average. In ALI the combination of ASD and language impairment was associated with weaker functional communication and more severe receptive language difficulties than those found in SLI. Receptive and expressive language were equally impaired in ALI, whereas in SLI receptive language was stronger than expressive. Conclusions: Co-occurrence of ASD and language impairment is not associated with increased current autistic symptomatology but appears to be associated with greater impairment in receptive language and functional communication.

Mothers' attributions following their child's diagnosis of autistic spectrum disorder: exploring links with maternal levels of stress, depression and expectations about their child's future

Although the impact of autism spectrum disorders (ASDs) on the family is well recognized, the way mothers attempt to make sense of the diagnosis is largely unexplored. However, in other disabilities, attributions have been shown to predict a variety of outcomes including maternal wellbeing and engagement in treatment. Using Weiner's (198S) three-dimensional model, 16 mothers were interviewed to examine the nature and impact of their beliefs about their child's ASD using semi-structured interviews and measures of depression, parenting stress and expectations for their child's future. The findings suggested that mothers made a diverse and complex range of attributions that were consistent with Weiner's dimensions of locus of cause, stability and controllability. The nature of their attributions reflected particular difficulties associated with ASDs, such as uncertainties regarding cause and prognosis. Taking account of mothers' search for meaning will better enable professionals to support families following diagnosis.

Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome

Genetic studies of autism spectrum conditions (ASC) have mostly focused on the "low functioning" severe clinical subgroup, treating it as a rare disorder. However, ASC is now thought to be relatively common ( approximately 1%), and representing one end of a quasi-normal distribution of autistic traits in the general population. Here we report a study of common genetic variation in candidate genes associated with autistic traits and Asperger syndrome (AS). We tested single nucleotide polymorphisms in 68 candidate genes in three functional groups (sex steroid synthesis/transport, neural connectivity, and social-emotional responsivity) in two experiments. These were (a) an association study of relevant behavioral traits (the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ)) in a population sample (n=349); and (b) a case-control association study on a sample of people with AS, a "high-functioning" subgroup of ASC (n=174). 27 genes showed a nominally significant association with autistic traits and/or ASC diagnosis. Of these, 19 genes showed nominally significant association with AQ/EQ. In the sex steroid group, this included ESR2 and CYP11B1. In the neural connectivity group, this included HOXA1, NTRK1, and NLGN4X. In the socio-responsivity behavior group, this included MAOB, AVPR1B, and WFS1. Fourteen genes showed nominally significant association with AS. In the sex steroid group, this included CYP17A1 and CYP19A1. In the socio-emotional behavior group, this included OXT. Six genes were nominally associated in both experiments, providing a partial replication. Eleven genes survived family wise error rate (FWER) correction using permutations across both experiments, which is greater than would be expected by chance. CYP11B1 and NTRK1 emerged as significantly associated genes in both experiments, after FWER correction (P<0.05). This is the first candidate-gene association study of AS and of autistic traits. The most promising candidate genes require independent replication and fine mapping.

Impairment in movement skills of children with autistic spectrum disorders

We undertook this study to explore the degree of impairment in movement skills in children with autistic spectrum disorders (ASD) and a wide IQ range. Movement skills were measured using the Movement Assessment Battery for Children (M-ABC) in a large, well defined, population-derived group of children (n=101: 89 males,12 females; mean age 11y 4mo, SD 10mo; range 10y-14y 3mo) with childhood autism and broader ASD and a wide range of IQ scores. Additionally, we tested whether a parent-completed questionnaire, the Developmental Coordination Disorder Questionnaire (DCDQ), was useful in identifying children who met criteria for movement impairments after assessment (n=97 with complete M-ABCs and DCDQs). Of the children with ASD, 79% had definite movement impairments on the M-ABC; a further 10% had borderline problems. Children with childhood autism were more impaired than children with broader ASD, and children with an IQ less than 70 were more impaired than those with IQ more than 70. This is consistent with the view that movement impairments may arise from a more severe neurological impairment that also contributes to intellectual disability and more severe autism. Movement impairment was not associated with everyday adaptive behaviour once the effect of IQ was controlled for. The DCDQ performed moderately well as a screen for possible motor difficulties. Movement impairments are common in children with ASD. Systematic assessment of movement abilities should be considered a routine investigation.

Efficacy of three screening instruments in the identification of autistic-spectrum disorders

Background Screening instruments for autistic-spectrum disorders have not been compared in the same sample. Aims To compare the Social Communication Questionnaire (SCQ), the Social Responsiveness Scale (SRS) and the Children's Communication Checklist (CCC). Method Screen and diagnostic assessments on 119 children between 9 and 13 years of age with special educational needs with and without autistic-spectrum disorders were weighted to estimate screen characteristics for a realistic target population. Results The SCQ performed best (area under receiver operating characteristic curve (AUC)=0.90; sensitivity. 6; specificity 0.78). The SRS had a lower AUC (0.77) with high sensitivity (0.78) and moderate specificity (0.67). The CCC had a high sensitivity but lower specificity (AUC=0.79; sensitivity 0.93; specificity 0.46). The AUC of the SRS and CCC was lower for children with IQ < 70. Behaviour problems reduced specificity for all three instruments. Conclusions The SCQ, SRS and CCC showed strong to moderate ability to identify autistic-spectrum disorder in this at-risk sample of school-age children with special educational needs.

Securing provision for children with autistic spectrum disorders: the views of parents

An original questionnaire was designed to seek the perspectives of parents about the process of securing appropriate educational provision for their child with autism spectrum disorder. In total, 738 responses were analysed using both quantative and qualitative data. Although a broad range of opinion was evidenced and a clear majority of families were happy with the end decision of placement, most families were significantly less happy with the process to determine that provision. Most families found this process difficult to navigate and frustrating. This caused a high level of stress for a significant proportion of families. Implications for practice are discussed.

Which words are hard for autistic children to learn?

Motivated by accounts of concept use in autistic spectrum disorder (ASD), and a computational model of weak central coherence (O’Loughlin & Thagard, 2000) we examined comprehension and production vocabulary in typically-developing children, and those with ASD and Down syndrome (DS). Controlling for frequency, familiarity, length, and imageability, Colorado Meaningfulness played a hitherto unremarked role in the vocabularies of children with ASD. High Colorado Meaningful words were underrepresented in the comprehension vocabularies of 2- to 12-year-olds with ASD. The Colorado Meaningfulness of a word is a measure of how many words can be associated with it. Situations in which high Colorado Meaningfulness words are encountered are typically highly variable, and words with High Colorado Meaningfulness often involve extensive use of context. Our data suggest that the number of contexts in which a particular word can appear has a role in determining vocabulary in ASD. This suggestion is consistent with the weak central coherence theory of autism.

Frontal networks in adults with autism spectrum disorder

It has been postulated that autism spectrum disorder is underpinned by an ‘atypical connectivity’ involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a ‘whole brain’ non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate—predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

A Functional Magnetic Resonance Imaging Predictor of Treatment Response to Venlafaxine in Generalized Anxiety Disorder

Background: Functional magnetic resonance imaging (fMRI) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial. Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex (ACC). Here, we sought to determine whether pretreatment amygdala and rostral ACC (rACC) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder (GAD).Methods: Fifteen subjects (12 female subjects) with GAD participated in an open-label venlafaxine treatment trial. Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration. In addition, the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects (12 female subjects) who did not have GAD and did not receive venlafaxine treatment.Results The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala. These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group.Conclusions: These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD.

Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate.

We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing, decreased tolerance to delays, poor temporal foresight and steeper temporal discounting. A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder (ADHD). Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD. We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal, cingulate, striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds, motor timing to seconds and temporal discounting of longer time intervals. Given that impulsiveness, timing abnormalities and more specifically ADHD have been related to dopamine dysregulation, we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice, methylphenidate. This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor.

Intrinsic disorder prediction from the analysis of multiple protein fold recognition models

Motivation: Intrinsic protein disorder is functionally implicated in numerous biological roles and is, therefore, ubiquitous in proteins from all three kingdoms of life. Determining the disordered regions in proteins presents a challenge for experimental methods and so recently there has been much focus on the development of improved predictive methods. In this article, a novel technique for disorder prediction, called DISOclust, is described, which is based on the analysis of multiple protein fold recognition models. The DISOclust method is rigorously benchmarked against the top.ve methods from the CASP7 experiment. In addition, the optimal consensus of the tested methods is determined and the added value from each method is quantified. Results: The DISOclust method is shown to add the most value to a simple consensus of methods, even in the absence of target sequence homology to known structures. A simple consensus of methods that includes DISOclust can significantly outperform all of the previous individual methods tested.

Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children

Children with autistic spectrum disorders (ASDs) tend to suffer from severe gastrointestinal problems. Such symptoms may be due to a disruption of the indigenous gut flora promoting the overgrowth of potentially pathogenic micro-organisms. The faecal flora of patients with ASDs was studied and compared with those of two control groups (healthy siblings and unrelated healthy children). Faecal bacterial populations were assessed through the use of a culture-independent technique, fluorescence in situ hybridization, using oligonucleotide probes targeting predominant components of the gut flora. The faecal flora of ASD patients contained a higher incidence of the Clostridium histolyticum group (Clostridium clusters I and 11) of bacteria than that of healthy children. However, the non-autistic sibling group had an intermediate level of the C. histolyticum group, which was not significantly different from either of the other subject groups. Members of the C. histolyticum group are recognized toxin-producers and may contribute towards gut dysfunction, with their metabolic products also exerting systemic effects. Strategies to reduce clostridial population levels harboured by ASD patients or to improve their gut microflora profile through dietary modulation may help to alleviate gut disorders common in such patients.

Disorder and dissolution enhancement: Deposition of ibuprofen on to insoluble polymers

Microcrystalline cellulose (MCC) and cross-linked polyvinylpyrrolidone (PVP-CL) were examined as polymeric carriers to support amorphous ibuprofen (IB). Drug/cartier systems were prepared as physical mixes, and drug was loaded onto the polymers by hot mix and solvent deposition methods. The systems were examined using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD) and by dissolution testing. PVP-CL reduced drug crystallinity more than MCC and, surprisingly, even very simple mixing of ibuprofen with PVP-CL induced disordering of the drug. Increased ibuprofen dissolution rates were achieved with both polymers, in the order of solvent deposition > hot mixes > physical mixes. The increased dissolution rates could be attributed to a combination of faster dissolution from amorphous ibuprofen, microcrystalline drug deposition on carrier surfaces and polymer swelling. However, no clear relationship was observed between ibuprofen dissolution rates (using first order, Higuchi or Hixson-Crowell relationships) and drug crystallinity. (C) 2005 Elsevier B.V. All rights reserved.