Abnormalities In Autism Spectrum Disorder Research Articles

Neural networks related to dysfunctional face processing in autism spectrum disorder.

One of the most consistent neuropsychological findings in autism spectrum disorders (ASD) is a reduced interest in and impaired processing of human faces. We conducted an activation likelihood estimation meta-analysis on 14 functional imaging studies on neural correlates of face processing enrolling a total of 164 ASD patients. Subsequently, normative whole-brain functional connectivity maps for the identified regions of significant convergence were computed for the task-independent (resting-state) and task-dependent (co-activations) state in healthy subjects. Quantitative functional decoding was performed by reference to the BrainMap database. Finally, we examined the overlap of the delineated network with the results of a previous meta-analysis on structural abnormalities in ASD as well as with brain regions involved in human action observation/imitation. We found a single cluster in the left fusiform gyrus showing significantly reduced activation during face processing in ASD across all studies. Both task-dependent and task-independent analyses indicated significant functional connectivity of this region with the temporo-occipital and lateral occipital cortex, the inferior frontal and parietal cortices, the thalamus and the amygdala. Quantitative reverse inference then indicated an association of these regions mainly with face processing, affective processing, and language-related tasks. Moreover, we found that the cortex in the region of right area V5 displaying structural changes in ASD patients showed consistent connectivity with the region showing aberrant responses in the context of face processing. Finally, this network was also implicated in the human action observation/imitation network. In summary, our findings thus suggest a functionally and structurally disturbed network of occipital regions related primarily to face (but potentially also language) processing, which interact with inferior frontal as well as limbic regions and may be the core of aberrant face processing and reduced interest in faces in ASD.

Precentral gyrus functional connectivity signatures of autism.

Motor impairments are prevalent in children with autism spectrum disorders (ASD) and are perhaps the earliest symptoms to develop. In addition, motor skills relate to the communicative/social deficits at the core of ASD diagnosis, and these behavioral deficits may reflect abnormal connectivity within brain networks underlying motor control and learning. Despite the fact that motor abnormalities in ASD are well-characterized, there remains a fundamental disconnect between the complexity of the clinical presentation of ASD and the underlying neurobiological mechanisms. In this study, we examined connectivity within and between functional subregions of a key component of the motor control network, the precentral gyrus, using resting state functional Magnetic Resonance Imaging data collected from a large, heterogeneous sample of individuals with ASD as well as neurotypical controls. We found that the strength of connectivity within and between distinct functional subregions of the precentral gyrus was related to ASD diagnosis and to the severity of ASD traits. In particular, connectivity involving the dorsomedial (lower limb/trunk) subregion was abnormal in ASD individuals as predicted by models using a dichotomous variable coding for the presence of ASD, as well as models using symptom severity ratings. These findings provide further support for a link between motor and social/communicative abilities in ASD.

Longitudinal changes in cortical thickness in autism and typical development.

The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.

Environmental toxicants and autism spectrum disorders: a systematic review

Although the involvement of genetic abnormalities in autism spectrum disorders (ASD) is well-accepted, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. However, these toxicant-related studies in ASD have not been systematically reviewed to date. Therefore, we compiled publications investigating potential associations between environmental toxicants and ASD and arranged these publications into the following three categories: (a) studies examining estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; (b) studies investigating biomarkers of toxicants; and (c) studies examining potential genetic susceptibilities to toxicants. A literature search of nine electronic scientific databases through November 2013 was performed. In the first category examining ASD risk and estimated toxicant exposures in the environment, the majority of studies (34/37; 92%) reported an association. Most of these studies were retrospective case–control, ecological or prospective cohort studies, although a few had weaker study designs (for example, case reports or series). Toxicants implicated in ASD included pesticides, phthalates, polychlorinated biphenyls (PCBs), solvents, toxic waste sites, air pollutants and heavy metals, with the strongest evidence found for air pollutants and pesticides. Gestational exposure to methylmercury (through fish exposure, one study) and childhood exposure to pollutants in water supplies (two studies) were not found to be associated with ASD risk. In the second category of studies investigating biomarkers of toxicants and ASD, a large number was dedicated to examining heavy metals. Such studies demonstrated mixed findings, with only 19 of 40 (47%) case–control studies reporting higher concentrations of heavy metals in blood, urine, hair, brain or teeth of children with ASD compared with controls. Other biomarker studies reported that solvent, phthalate and pesticide levels were associated with ASD, whereas PCB studies were mixed. Seven studies reported a relationship between autism severity and heavy metal biomarkers, suggesting evidence of a dose–effect relationship. Overall, the evidence linking biomarkers of toxicants with ASD (the second category) was weaker compared with the evidence associating estimated exposures to toxicants in the environment and ASD risk (the first category) because many of the biomarker studies contained small sample sizes and the relationships between biomarkers and ASD were inconsistent across studies. Regarding the third category of studies investigating potential genetic susceptibilities to toxicants, 10 unique studies examined polymorphisms in genes associated with increased susceptibilities to toxicants, with 8 studies reporting that such polymorphisms were more common in ASD individuals (or their mothers, 1 study) compared with controls (one study examined multiple polymorphisms). Genes implicated in these studies included paraoxonase (PON1, three of five studies), glutathione S-transferase (GSTM1 and GSTP1, three of four studies), δ-aminolevulinic acid dehydratase (one study), SLC11A3 (one study) and the metal regulatory transcription factor 1 (one of two studies). Notably, many of the reviewed studies had significant limitations, including lack of replication, limited sample sizes, retrospective design, recall and publication biases, inadequate matching of cases and controls, and the use of nonstandard tools to diagnose ASD. The findings of this review suggest that the etiology of ASD may involve, at least in a subset of children, complex interactions between genetic factors and certain environmental toxicants that may act synergistically or in parallel during critical periods of neurodevelopment, in a manner that increases the likelihood of developing ASD. Because of the limitations of many of the reviewed studies, additional high-quality epidemiological studies concerning environmental toxicants and ASD are warranted to confirm and clarify many of these findings.

Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2–3 Years Old Toddlers

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships in adolescents and adults with ASD, literature is still limited in information about the neurobiology of ASD in the early age of life. Brain images of 50 toddlers with ASD and 28 age, gender, and developmental quotient matched toddlers with developmental delay (DD) (control group) between ages 2 and 3 years were captured using combined magnetic resonance-based structural imaging and diffusion tensor imaging (DTI). Structural magnetic resonance imaging was applied to assess overall gray matter (GM) and white matter (WM) volumes, and regional alterations were assessed by voxel-based morphometry. DTI was used to investigate the white matter tract integrity. Compared with DD, significant increases were observed in ASD, primarily in global GM and WM volumes and in right superior temporal gyrus regional GM and WM volumes. Higher fractional anisotropy value was also observed in the corpus callosum, posterior cingulate cortex, and limbic lobes of ASD. The converging findings of structural and white matter abnormalities in ASD suggest that alterations in neural-anatomy of different brain regions may be involved in behavioral and cognitive deficits associated with ASD, especially in an early age of 2–3 years old toddlers.

Resting state EEG abnormalities in autism spectrum disorders

Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD.

Neuromagnetic Oscillations Predict Evoked-Response Latency Delays and Core Language Deficits in Autism Spectrum Disorders

Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a 'core' abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate 'neural tone' and an inability to rapidly return to a resting state prior to the next stimulus.

Concordance of white matter and gray matter abnormalities in autism spectrum disorders: A voxel‐based meta‐analysis study

There are at least two fundamental unanswered questions in the literature on autism spectrum disorders (ASD): Are abnormalities in white (WM) and gray matter (GM) consistent with one another? Are WM morphometric alterations consistent with alterations in the GM of regions connected by these abnormal WM bundles and vice versa? The aim of this work is to bridge this gap. After selecting voxel-based morphometry and diffusion tensor imaging studies comparing autistic and normally developing groups of subjects, we conducted an activation likelihood estimation (ALE) meta-analysis to estimate consistent brain alterations in ASD. Multidimensional scaling was used to test the similarity of the results. The ALE results were then analyzed to identify the regions of concordance between GM and WM areas. We found statistically significant topological relationships between GM and WM abnormalities in ASD. The most numerous were negative concordances, found bilaterally but with a higher prevalence in the right hemisphere. Positive concordances were found in the left hemisphere. Discordances reflected the spatial distribution of negative concordances. Thus, a different hemispheric contribution emerged, possibly related to pathogenetic factors affecting the right hemisphere during early developmental stages. Besides, WM fiber tracts linking the brain structures involved in social cognition showed abnormalities, and most of them had a negative concordance with the connected GM regions. We interpreted the results in terms of altered brain networks and their role in the pervasive symptoms dramatically impairing communication and social skills in ASD patients.

Abnormal Pre-Attentive Arousal in Young Children with Autism Spectrum Disorder Contributes to Their Atypical Auditory Behavior: An ERP Study

Auditory sensory modulation difficulties and problems with automatic re-orienting to sound are well documented in autism spectrum disorders (ASD). Abnormal preattentive arousal processes may contribute to these deficits. In this study, we investigated components of the cortical auditory evoked potential (CAEP) reflecting preattentive arousal in children with ASD and typically developing (TD) children aged 3-8 years. Pairs of clicks (‘S1’ and ‘S2’) separated by a 1 sec S1-S2 interstimulus interval (ISI) and much longer (8-10 sec) S1-S1 ISIs were presented monaurally to either the left or right ear. In TD children, the P50, P100 and N1c CAEP components were strongly influenced by temporal novelty of clicks and were much greater in response to the S1 than the S2 click. Irrespective of the stimulation side, the ‘tangential’ P100 component was rightward lateralized in TD children, whereas the ‘radial’ N1c component had higher amplitude contralaterally to the stimulated ear. Compared to the TD children, children with ASD demonstrated 1) reduced amplitude of the P100 component under the condition of temporal novelty (S1) and 2) an attenuated P100 repetition suppression effect. The abnormalities were lateralized and depended on the presentation side. They were evident in the case of the left but not the right ear stimulation. The P100 abnormalities in ASD correlated with the degree of developmental delay and with the severity of auditory sensory modulation difficulties observed in early life. The results suggest that some rightward-lateralized brain networks that are crucially important for arousal and attention re-orienting are compromised in children with ASD and that this deficit contributes to sensory modulation difficulties and possibly even other behavioral deficits in ASD.

Incidence and Behavioral Correlates of Epileptiform Abnormalities in Autism Spectrum Disorders

Autism spectrum disorders (ASD) are associated with an increased incidence of epilepsy and of epileptiform discharges on electroencephalograms. It is unknown whether epileptiform discharges correlate with symptoms of ASD. We completed a retrospective chart review of 101 patients with ASD who had overnight electroencephalograms. We looked for a relationship between epileptiform abnormalities and diagnosis, history of regression, communication skills, and other features associated with ASD. There was a higher incidence of epileptiform activity in children with stereotypies and aggressive behavior. The incidence of epileptiform abnormalities was significantly lower in Asperger's compared with more severe forms of autism. Results suggest that increasing severity of autistic symptoms may be associated with higher likelihood of epileptiform abnormalities. Whether treatment alters outcome is unknown.

A substantial and unexpected enhancement of motion perception in autism.

Atypical perceptual processing in autism spectrum disorder (ASD) is well documented. In addition, growing evidence supports the hypothesis that an excitatory/inhibitory neurochemical imbalance might underlie ASD. Here we investigated putative behavioral consequences of the excitatory/inhibitory imbalance in the context of visual motion perception. As stimulus size increases, typical observers exhibit marked impairments in perceiving motion of high-contrast stimuli. This result, termed "spatial suppression," is believed to reflect inhibitory motion-processing mechanisms. Motion processing is also affected by gain control, an inhibitory mechanism that underlies saturation of neural responses at high contrast. Motivated by these behavioral correlates of inhibitory function, we investigated motion perception in human children with ASD (n = 20) and typical development (n = 26). At high contrast, both groups exhibited similar impairments in motion perception with increasing stimulus size, revealing no apparent differences in spatial suppression. However, there was a substantial enhancement of motion perception in ASD: children with ASD exhibited a consistent twofold improvement in perceiving motion. Hypothesizing that this enhancement might indicate abnormal weakening of response gain control, we repeated our measurements at low contrast, where the effects of gain control should be negligible. At low contrast, we indeed found no group differences in motion discrimination thresholds. These low-contrast results, however, revealed weaker spatial suppression in ASD, suggesting the possibility that gain control abnormalities in ASD might have masked spatial suppression differences at high contrast. Overall, we report a pattern of motion perception abnormalities in ASD that includes substantial enhancements at high contrast and is consistent with an underlying excitatory/inhibitory imbalance.

Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay

BackgroundHaploinsufficiency of SHANK3, due to either hemizygous gene deletion (termed 22q13 deletion syndrome or Phelan-McDermid syndrome) or to gene mutation, accounts for about 0.5% of the cases of autism spectrum disorder (ASD) and/or developmental delay, and there is evidence for a wider role for SHANK3 and glutamate signaling abnormalities in ASD and related conditions. Therapeutic approaches that reverse deficits in SHANK3-haploinsufficiency may therefore be broadly beneficial in ASD and in developmental delay.FindingsWe observed that daily intraperitoneal injections of human insulin-like growth factor 1 (IGF-1) over a 2-week period reversed deficits in hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) signaling, long-term potentiation (LTP), and motor performance that we had previously reported in Shank3-deficient mice. Positive effects were observed with an IGF-1 peptide derivative as well.ConclusionsWe observed significant beneficial effects of IGF-1 in a mouse model of ASD and of developmental delay. Studies in mouse and human neuronal models of Rett syndrome also show benefits with IGF-1, raising the possibility that this compound may have benefits broadly in ASD and related conditions, even with differing molecular etiology. Given the extensive safety data for IGF-1 in children with short stature due to primary IGF-1 deficiency, IGF-1 is an attractive candidate for controlled clinical trials in SHANK3-deficiency and in ASD.

Altered oscillation patterns and connectivity during picture naming in autism

Similar behavioral deficits are shared between individuals with autism spectrum disorders (ASD) and their first-degree relatives, such as impaired face memory, object recognition, and some language aspects. Functional neuroimaging studies have reported abnormalities in ASD in at least one brain area implicated in those functions, the fusiform gyrus (FG). High frequency oscillations have also been described as abnormal in ASD in a separate line of research. The present study examined whether low- and high-frequency oscillatory power, localized in part to FG and other language-related regions, differs in ASD subjects and first-degree relatives. Twelve individuals with ASD, 16 parents of children with ASD, and 35 healthy controls participated in a picture-naming task using magnetoencephalography (MEG) to assess oscillatory power and connectivity. Relative to controls, we observed reduced evoked high-gamma activity in the right superior temporal gyrus (STG) and reduced high-beta/low-gamma evoked power in the left inferior frontal gyrus (IFG) in the ASD group. Finally, reductions in phase-locked beta-band were also seen in the ASD group relative to controls, especially in the occipital lobes (OCC). First degree relatives, in contrast, exhibited higher high-gamma band power in the left STG compared with controls, as well as increased high-beta/low-gamma evoked power in the left FG. In the left hemisphere, beta- and gamma-band functional connectivity between the IFG and FG and between STG and OCC were higher in the autism group than in controls. This suggests that, contrary to what has been previously described, reduced connectivity is not observed across all scales of observation in autism. The lack of behavioral correlation for the findings warrants some caution in interpreting the relevance of such changes for language function in ASD. Our findings in parents implicates the gamma- and beta-band ranges as potential compensatory phenomena in autism relatives.

Immunological Abnormalities in Autism Spectrum Disorders

Secondary to clinical features indicating chronic inflammation and immune dysregulation, the immune system has long been suspected to have a role in autism spectrum disorders (ASD). Studies of postmortem autistic brains indicate the presence of immune mediated chronic inflammation in some but not all autistic brains. However, studies of immune abnormalities in ASD children yielded no conclusive results. Instead, immune abnormalities reported appear to affect almost all aspects of the immune system and are often contradictory. This may be associated with the marked heterogeneity of ASD subjects, since ASD is a behaviorally defined syndrome. In addition, variable co-morbid conditions could affect the immune-parameters, making such analysis very difficult. Alternatively, various immune abnormalities reported may be associated with the fact that ASD is a polygenic condition affected by multiple genetic and environmental factors, resulting in similar behavioral symptoms. At present, it is unknown how the immune system contributes to the onset and progress of ASD. Nevertheless, the results of previous studies indicate the presence of chronic inflammation, in at least a portion of ASD children. This review summarizes previous immunological findings and the problems associated with these studies. The direction that future research needs to take will also be discussed.

Rhythm, movement, and autism: using rhythmic rehabilitation research as a model for autism.

Recently, there has been increased focus on movement and sensory abnormalities in autism spectrum disorders (ASD). This has come from research demonstrating cortical and cerebellar differences in autism, with suggestion of early cerebellar dysfunction. As evidence for an extended profile of ASD grows, there are vast implications for treatment and therapy for individuals with autism. Persons with autism are often provided behavioral or cognitive strategies for navigating their environment; however, these strategies do not consider differences in motor functioning. One accommodation that has not yet been explored in the literature is the use of auditory rhythmic cueing to improve motor functioning in ASD. The purpose of this paper is to illustrate the potential impact of auditory rhythmic cueing for motor functioning in persons with ASD. To this effect, we review research on rhythm in motor rehabilitation, draw parallels to motor dysfunction in ASD, and propose a rationale for how rhythmic input can improve sensorimotor functioning, thereby allowing individuals with autism to demonstrate their full cognitive, behavioral, social, and communicative potential.

Autism, social cognition and superior temporal sulcus

Results on brain imaging studies have led to a better understanding of the neural circuits involved in social cognition and its implication in autism spectrum disorders(ASD). It has been shown that the superior temporal sulcus(STS)is highly implicated in social processes, from perception of socially relevant information, such as body movements or eye gaze, to more complex social cognition processes. Furthermore, several multimodal brain imaging results point to anatomo-functional abnormalities in the STS in both children and adults with ASD. These results are highly consistent with social impairments in ASD, among which eye gaze perception is particularly relevant. Gaze abnormalities can now be objectively measured using eye-tracking methodology, leading to a better characterization of social perception impairments in autism. Moreover, these gaze abnormalities have been associated with STS abnormalities in ASD. Based on these results, our hypothesis is that anatomo-functional anomalies in the STS occurring early across brain development could constitute the first step in the cascade of neural dysfunction underlying autism. In the present work, we’ll review recent data of STS contribution to normal social cognition and it’s implication in autism.

Studying gaze abnormalities in autism: Which type of stimulus to use?

Background: Eye-tracking has been used to investigate social perception in autism spectrum disorder (ASD) with variable results. This heterogeneity may be due to the types of stimuli used. In this study, we investigated whether the use of moving vs static stimuli or human actors vs cartoons characters would be more sensitive in detecting gaze abnormalities and discriminating children with ASD from typically developing children. Methods: We studied 18 children with ASD (mean age = 12.9 ± 2.9) and 21 typically developing controls (mean age = 11.3 ± 2.5). Gazes were tracked using Tobii-T120 eye-tracker. Four different types of stimuli were presented: movie with human actors, cartoon movie, picture with human actors and cartoon picture. To identify the type of stimuli that best discriminate the ASD group from the control group, a two-way ANOVA was performed using ecological dimension [human-actors/cartoon] and presentation form [movie/picture] as factors. Results: Children with ASD presented significantly less fixations to eyes and faces in the movie with human actors and in the picture with human actors. Children with ASD also presented significantly more fixations to non-social backgrounds in the movie with human actors and in the cartoon movie. A significant ecological effect was observed for the reduction in fixations to the eyes [human-actors > cartoon]. A significant presentation form effect was observed for the increased fixations to the non-social background [movie > picture]. Conclusions: The direct comparison of gaze behavior across four different types of stimuli demonstrates that gaze abnormalities in ASD depend on the type of stimuli that is used. Our results suggest that general gaze abnormalities in children with ASD are better detected when using dynamic stimuli, and finer details of these abnormalities, especially looking less to the eyes, are better detected in a more ecologically relevant situation presenting human characters.

Visual gain control abnormalities in Autism Spectrum Disorders

Limited population-based data on prevalence of childhood vision impairment (VI) and hearing loss (HL), and their co-occurrence with autism spectrum disorder (ASD) exists.To examine prevalence and characteristics of VI, HL and co-occurring ASD among 8-year-olds in metropolitan Atlanta 2000–2008.We used data from the population-based Metropolitan Atlanta Developmental Disabilities Surveillance Program. Prevalence, birth and parental characteristics, presence and severity of other co-occurring developmental disabilities, and age of earliest identification of ASD, were examined for children with VI and HL, by co-occurring ASD.VI and HL prevalences were 1.2 and 1.3 per 1000 8-year-olds, respectively. Approximately 6–7% of children with VI or HL had co-occurring ASD. Children with VI or HL with co-occurring ASD differed from those without co-occurring ASD by select birth characteristics and the presence of other co-occurring DDs. The median age of earliest known ASD diagnosis was significantly later among children with VI and ASD compared to children with ASD without VI (79 vs. 56 months). Children with HL and ASD were first evaluated by a community provider significantly earlier than those with ASD without HL (40 vs. 50 months).The frequency of co-occurring ASD with VI and HL is higher than the population prevalence of ASD. The significant delays in diagnosis of ASD in children with VI and lack of earlier diagnosis of ASD among children with HL despite earlier evaluation highlight the importance of developing screening tools for early identification of ASD among children with VI and HL.

Changes in grey matter development in autism spectrum disorder

Results on grey matter (GM) structural alterations in autism spectrum disorder (ASD) are inconclusive. Moreover, little is known about age effects on brain-structure abnormalities in ASD beyond childhood. Here, we aimed to examine regional GM volumes in a large sample of children, adolescents, and adults with ASD. Magnetic resonance imaging scans were obtained in 47 male ASD subjects and 51 matched healthy controls aged 8–50 years. We used whole-brain voxel-based morphometry to first assess group differences in regional GM volume across age. Moreover, taking a cross-sectional approach, group differences in age effects on regional GM volume were investigated. Compared to controls, ASD subjects showed reduced GM volumes in the anterior cingulate cortex, posterior superior temporal sulcus, and middle temporal gyrus. Investigation of group differences in age effects on regional GM volume revealed complex, region-specific alterations in ASD. While GM volumes in the amygdala, temporoparietal junction, septal nucleus and middle cingulate cortex increased in a negative quadratic fashion in both groups, data indicated that GM volume curves in ASD subjects were shifted to the left along the age axis. Moreover, while GM volume in the right precentral gyrus decreased linearly with age in ASD individuals, GM volume development in controls followed a U-shaped pattern. Based on a large sample, our voxel-based morphometry results on group differences in regional GM volumes help to resolve inconclusive findings from previous studies in ASD. Results on age-related changes of regional GM volumes suggest that ASD is characterized by complex alterations in lifetime trajectories of several brain regions that underpin social-cognitive and motor functions.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-012-0439-9) contains supplementary material, which is available to authorized users.

Maternal autoantibodies in autism.

As epidemiologic studies continue to note a striking increase in rates of autism spectrum disorder (ASD) diagnosis around the world, the lack of identified causative agents in most cases remains a major hindrance to the development of treatment and prevention strategies. Published observations of immune system abnormalities in ASD have increased recently, with several groups identifying fetal protein reactive IgG antibodies in plasma from mothers of children with autism. Furthermore, other gestational immune parameters, including maternal infection and dysregulated cytokine signaling, have been found to be associated with ASD in some cases. While detailed pathogenic mechanisms remain to be determined, the hypothesis that some cases of ASD may be influenced, or even caused, by maternal fetal brain-reactive antibodies or other in utero immune-related exposures is an active area of investigation. This article reviews the current literature in this area and proposes several directions for future research.