Sara Calderoni

White matter connectivity in children with Autism spectrum disorders: a tract-based spatial statistics study

BackgroundAutism spectrum disorders (ASD) are associated with widespread alterations in white matter (WM) integrity. However, while a growing body of studies is shedding light on microstructural WM alterations in high-functioning adolescents and adults with ASD, literature is still lacking in information about whole brain structural connectivity in children and low-functioning patients with ASD. This research aims to investigate WM connectivity in ASD children with and without mental retardation compared to typically developing controls (TD).MethodsDiffusion tensor imaging (DTI) was performed in 22 young children with ASD (mean age: 5.54 years) and 10 controls (mean age: 5.25 years). Data were analysed both using the tract-based spatial statistics (TBSS) and the tractography. Correlations were investigated between the WM microstructure in the identified altered regions and the productive language level.ResultsThe TBSS analysis revealed widespread increase of fractional anisotropy (FA) in major WM pathways. The tractographic approach showed an increased fiber length and FA in the cingulum and in the corpus callosum and an increased mean diffusivity in the indirect segments of the right arcuate and the left cingulum. Mean diffusivity was also correlated with expressive language functioning in the left indirect segments of the arcuate fasciculus.ConclusionsOur study confirmed the presence of several structural connectivity abnormalities in young ASD children. In particular, the TBSS profile of increased FA that characterized the ASD patients extends to children a finding previously detected in ASD toddlers only. The WM integrity abnormalities detected may be relevant to the pathophysiology of ASD, since the structures involved participate in some core atypical characteristics of the disorder.

Female children with autism spectrum disorder: an insight from mass-univariate and pattern classification analyses.

Several studies on structural MRI in children with autism spectrum disorders (ASD) have mainly focused on samples prevailingly consisting of males. Sex differences in brain structure are observable since infancy and therefore caution is required in transferring to females the results obtained for males. The neuroanatomical phenotype of female children with ASD (ASDf) represents indeed a neglected area of research. In this study, we investigated for the first time the anatomic brain structures of a sample entirely composed of ASDf (n=38; 2-7 years of age; mean=53 months; SD=18) with respect to 38 female age and non verbal IQ matched controls, using both mass-univariate and pattern classification approaches. The whole brain volumes of each group were compared using voxel-based morphometry (VBM) with diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure, allowing us to build a study-specific template. Significantly more gray matter (GM) was found in the left superior frontal gyrus (SFG) in ASDf subjects compared to controls. The GM segments obtained in the VBM-DARTEL preprocessing are also classified with a support vector machine (SVM), using the leave-pair-out cross-validation protocol. Then, the recursive feature elimination (SVM-RFE) approach allows for the identification of the most discriminating voxels in the GM segments and these prove extremely consistent with the SFG region identified by the VBM analysis. Furthermore, the SVM-RFE map obtained with the most discriminating set of voxels corresponding to the maximum Area Under the Receiver Operating Characteristic Curve (AUC(max)=0.80) highlighted a more complex circuitry of increased cortical volume in ASDf, involving bilaterally the SFG and the right temporo-parietal junction (TPJ). The SFG and TPJ abnormalities may be relevant to the pathophysiology of ASDf, since these structures participate in some core atypical features of autism.

The CBCL 1.5-5 and the identification of preschoolers with autism in Italy.

AIMS To study the potential use of child behaviour checklist (CBCL) 1.5-5 scales for the early identification of preschoolers at risk of autism. METHODS CBCL scores of three groups of preschoolers were compared: (1) an experimental group of 101 preschoolers with autism spectrum disorder (ASD); (2) a control group of 95 preschoolers with other psychiatric disorders (OPD); (3) a control group of 117 preschoolers with typical development (TD). One-way analysis of variance (ANOVA), logistic regression with odds ratio (OR) and receiver operating characteristic (ROC) analyses were performed. RESULTS ANOVA revealed that ASD and OPD had significantly higher scores in almost all CBCL scales than TD. ASD presented significantly higher scores than OPD on Withdrawn, Attention Problems and Pervasive Developmental Problems (PDP) scales. Logistic regression analysis demonstrated that these same CBCL scales have validity in predicting the presence of an ASD towards both TD and OPD. ROC analysis indicated high sensitivity and specificity for PDP (0.85 and 0.90) and Withdrawn (0.89 and 0.92) scales when ASD is compared to TD. Specificity (0.60 for PDP and 0.65 for Withdrawn) decreases when comparing ASD and OPD CONCLUSIONS: The PDP and Withdrawn scales have a good predictive validity so that they could be proposed as a first-level tool to identify preschoolers at risk of autism in primary care settings. Problems regarding the lower specificity when comparing ASD v. OPD are discussed.

Neuropsychological profile in high functioning autism spectrum disorders.

A comprehensive investigation of the neuropsychological strengths and weaknesses of children with autism may help to better describe their cognitive abilities and to design appropriate interventions. To this end we compared the NEPSY-II profiles of 22 children with high-functioning autism spectrum disorders (HFASD) with those of 44 healthy control (HC) children 2:1 matched by gender, age, race and education. Results showed that only Visuospatial Processing was relatively spared in HFASD, while deficits were observed in Attention and Executive Functions, Language, Learning and Memory, and Sensorimotor Processing. Theory of Mind difficulties were observed in verbal tasks but not in the understanding of emotional contexts, suggesting that appropriate contextual cues might help emotion understanding in HFASD children. These widespread neuropsychological impairments reflect alterations in multiple cognitive domains in HFASD.

On the application of quantitative EEG for characterizing autistic brain: a systematic review

Autism-Spectrum Disorders (ASD) are thought to be associated with abnormalities in neural connectivity at both the global and local levels. Quantitative electroencephalography (QEEG) is a non-invasive technique that allows a highly precise measurement of brain function and connectivity. This review encompasses the key findings of QEEG application in subjects with ASD, in order to assess the relevance of this approach in characterizing brain function and clustering phenotypes. QEEG studies evaluating both the spontaneous brain activity and brain signals under controlled experimental stimuli were examined. Despite conflicting results, literature analysis suggests that QEEG features are sensitive to modification in neuronal regulation dysfunction which characterize autistic brain. QEEG may therefore help in detecting regions of altered brain function and connectivity abnormalities, in linking behavior with brain activity, and subgrouping affected individuals within the wide heterogeneity of ASD. The use of advanced techniques for the increase of the specificity and of spatial localization could allow finding distinctive patterns of QEEG abnormalities in ASD subjects, paving the way for the development of tailored intervention strategies.

Child Behavior Check List 1½-5 as a tool to identify toddlers with autism spectrum disorders: a case-control study.

Tools to identify toddlers with autism in clinical settings have been recently developed. This study evaluated the sensitivity and specificity of the Child Behavior Check List 1½-5 (CBCL 1½-5) in the detection of toddlers subsequently diagnosed with an Autism Spectrum Disorder (ASD), ages 18-36 months. The CBCL of 47 children with ASD were compared to the CBCL of 47 toddlers with Other Psychiatric Disorders (OPD) as well as the CBCL of 47 toddlers with Typical Development (TD) in a case control study. One-way analysis of variance (ANOVA) and logistic regression with odds ratio (OR) analyses were performed. In order to establish the optimal threshold able to discriminate children with ASD from children with OPD and TD, Receiver Operating Characteristic (ROC) analyses were performed. One-way ANOVA revealed significant differences between the three groups. Logistic regression analysis showed that the Withdrawn and the Pervasive Developmental Problems (PDP) subscales can recognize toddlers subsequently identified as ASD from both children with TD (p<0.001) and OPD (p<0.001). ROC analyses showed very high sensitivity and specificity for the PDP (0.98 and 0.91) and Withdrawn (0.92 and 0.97) subscales when ASD was compared to TD. Sensitivity and specificity of Withdrawn (0.90 and 0.83) and PDP (0.85 and 0.83) remained high when comparing ASD versus OPD. In conclusion, the CBCL 1½-5 seemed to be able to identify toddlers subsequently diagnosed with ASD from children with TD and OPD. Its high sensitivity and specificity, coupled with its efficiency in terms of time and cost, suggest this broadband tool should be tested in a pilot screening survey of toddlers in the general population.

Neuropsychological functioning in children and adolescents with restrictive-type anorexia nervosa: An in-depth investigation with NEPSY-II

Several studies have investigated the neuropsychological functioning of patients with anorexia nervosa restrictive type (AN-r), but results are conflicting. Here we compared the neuropsychological profile of 23 female children and adolescents with AN-r and of 46 typical controls (aged 9–16 years) using the second edition of the NEPSY (a Developmental Neuropsychology Assessment) neuropsychological battery. AN-r patients presented subtle cognitive flexibility impairments in audiomotor responses (p = .033). Conversely, superior performance in verbal fluency (p = .024) and memory (p = .034) was observed only in AN-r patients with an associated unipolar mood disorder. This profile of marginally impaired and enhanced performance was independent from illness duration and starvation degree, suggesting that it may preexist and represent a vulnerability factor for the disease onset.

Gray Matter Alterations in Young Children with Autism Spectrum Disorders: Comparing Morphometry at the Voxel and Regional Level.

Sophisticated algorithms to infer disease diagnosis, pathology progression and patient outcome are increasingly being developed to analyze brain MRI data. They have been successfully implemented in a variety of diseases and are currently investigated in the field of neuropsychiatric disorders, including autism spectrum disorder (ASD). We aim to test the ability to predict ASD from subtle morphological changes in structural magnetic resonance imaging (sMRI).

The first 1000 days of the autistic brain: a systematic review of diffusion imaging studies

There is overwhelming evidence that autism spectrum disorder (ASD) is related to altered brain connectivity. While these alterations are starting to be well characterized in subjects where the clinical picture is fully expressed, less is known on their earlier developmental course. In the present study we systematically reviewed current knowledge on structural connectivity in ASD infants and toddlers. We searched PubMed and Medline databases for all English language papers, published from year 2000, exploring structural connectivity in populations of infants and toddlers whose mean age was below 30 months. Of the 264 papers extracted, four were found to be eligible and were reviewed. Three of the four selected studies reported higher fractional anisotropy values in subjects with ASD compared to controls within commissural fibers, projections fibers, and association fibers, suggesting brain hyper-connectivity in the earliest phases of the disorder. Similar conclusions emerged from the other diffusion parameters assessed. These findings are reversed to what is generally found in studies exploring older patient groups and suggest a developmental course characterized by a shift toward hypo-connectivity starting at a time between two and four years of age.

Are children born after assisted reproductive technology at increased risk of autism spectrum disorders? A systematic review

STUDY QUESTION Are children born after assisted reproductive technology (ART) at increased risk of autism spectrum disorders (ASD)? SUMMARY ANSWER There is no evidence that ART significantly increases the risk of ASD in the offspring. WHAT IS KNOWN ALREADY A few systematic reviews have explored the correlation between assisted conception and ASD with inconclusive results, partly due to the heterogeneity of diagnostic criteria and methodology in the different studies. STUDY DESIGN, SIZE, DURATION Systematic review of 7 observational studies (2 cohort and 5 case-control) encompassing 9216 subjects diagnosed with ASD published since 2000. MATERIALS, SETTING, METHODS Literature searches were conducted to retrieve observational studies on the risk of ASD in ART population. Databases searched included PubMed, EMBASE and PsycINFO. In order to obtain more consistent results, we only included the studies in which (i) subjects with either infantile autism or ASD could be identified according to international classification systems and (ii) the diagnosis was obtained from hospital records. Seven studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE Four out of seven studies, including the two with the best quality scores, did not show an association between ART and ASD. The two papers supporting an increased risk of autism following ART had the lowest quality scores, due to major methodological limitations. Only one paper showed a protective role of ART. LIMITATIONS, REASONS FOR CAUTION In spite of the strict inclusion criteria applied as to the diagnosis of ASD, the papers selected are heterogeneous in many aspects including study design, definitions of ART, data source and analysed confounders. WIDER IMPLICATIONS OF THE FINDINGS At present, there is no evidence that ART is significantly associated with ASD and hence that current health policies should be modified. The divergent results of some of the studies suggest that further prospective, large and high-quality studies are still needed. STUDY FUNDING/COMPETING INTEREST(S) This work was supported, in part, by the Italian Ministry of Health and by Tuscany Region. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER N/A.