Raffaella Tancredi

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.

Spatial and motion integration in children with autism.

Neuropsychological and psychophysical studies report controversial results regarding local-global visual processing and motion perception in autism. Here, we investigate contour integration and motion perception in an accurately diagnosed sample of autistic children, using low-level psychophysical tasks. We measured detection thresholds for a closed chain of Gabor patches, for different values of inter-element distance and we measured coherency thresholds of optic flow motion stimuli. Both experiments show comparable performances between autistics and normal subjects, demonstrating no evidence of early perceptual integration deficits. Some improvement in performance with age is detected in both groups.

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.

Search superiority in autism within, but not outside the crowding regime

Visual cognition of observers with autism spectrum disorder (ASD) seems to show an unbalance between the complementary functions of integration and segregation. This study uses visual search and crowding paradigms to probe the relative ability of children with autism, compared to normal developments children, to extract individual targets from cluttered backgrounds both within and outside the crowding regime. The data show that standard search follows the same pattern in the ASD and control groups with a strong effect of the set size that is substantially weakened by cueing the target location with a synchronous spatial cue. On the other hand, the crowding effect of eight flankers surrounding a small peripheral target is virtually absent in the clinical sample, indicating a superior ability to segregate cluttered visual items. This data, along with evidence of an impairment to the neural system for binding contours in ASD, bring additional support to the general idea of a shift of the trade-off between integration and segregation toward the latter. More specifically, they show that when discriminability is balanced across conditions, an advantage in odd-man out tasks is evident in ASD observers only within the crowding regime, when binding mechanism might get compulsorily triggered in normal observers.

Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.

BackgroundWith a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly.MethodsWe analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly.ResultsAmong 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile (“extreme” macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with “extreme” macrocephaly, autism, intellectual disability and seizures.ConclusionsWe did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with “extreme” macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical endophenotypes might be of help to address genetic studies and establish actual causative correlations in autism-epilepsy.

Efficacy of Brief Dynamic Psychotherapy for Children with Emotional Disorders

Background: Child psychiatry has enjoyed a long tradition of using brief psychotherapy with children, but research on its efficacy and effectiveness in the setting of routine clinical care is remarkably sparse; the aim of this study was to evaluate the efficacy of an original model of brief psychodynamic psychotherapy (BPP) for children with emotional disorders in a clinical outpatient setting. Methods: A sample of 30 subjects (6.3–10.9 years old) was divided into an experimental BPP group and a control group. Each subject was evaluated at the beginning, after 6 months and at an 18-months follow-up. Outcome measures were Children’s Global Assessment Scale and Child Behavior Check-List. Statistical and clinical significance of change were evaluated. Results: At the first evaluation, the experimental group showed a better improvement in global functioning; at follow-up, the two groups improved to a comparable degree, but only the mean of the experimental group moved to a functional range. The experimental group showed a significant reduction in total behavioral problems and externalizing problems at the follow-up. Conclusions: The better improvement of the experimental group in two outcome measures suggests that BPP is efficient in emotional disorders. The hypothesis that BPP introduces changes at long term (sleeper effects) is suggested. The improvement in global functioning of the two groups is discussed in relation to specific characteristics of emotional disorders. Finally, limitations of the study are discussed and in particular the bias introduced by lack of randomization.

Neural correlates of texture and contour integration in children with autism spectrum disorders.

In this study, we have used an electrophysiological paradigm to investigate the neural correlates of the visual integration of local signals across space to generate global percepts in a group of low functioning autistic kids. We have analyzed the amplitude of key harmonics of the Visual Evoked Potentials (VEPs) recorded while participants observed orientation-based texture and contour stimuli, forming coherent global patterns, alternating with visual patterns in which the same number of local elements were randomly oriented in order to loose any globally organized feature. Comparing the results of the clinical sample with those obtained in an age-matched control group, we have observed that in the texture conditions the 1st and 3rd harmonics, containing signature of global form processing (Norcia, Pei, Bonneh, Hou, Sampath, & Pettet, 2005), were present in the control group, while in the experimental group only the 1st harmonic was present. In the Contour condition the 1st harmonic was not present for both groups while the 3rd harmonic was significantly present in the control group but absent in the group with autism. Moreover, the amount of organization required to elicit significant 1st harmonic response in the texture condition was higher in the clinical group. The present results bring additional support to the idea that texture and contour processing are supported by independent mechanisms in normal vision. Autistic vision would thus be characterized by a preserved, perhaps weaker texture mechanism, possibly mediated by feedback interactions between visual areas, and by a disfunction of the mechanism supporting contour processing, possibly mediated by long-range intra-cortical connections. Within this framework, the residual ability to detect contours shown in psychophysical studies could be due to the contribution of the texture mechanism to contour processing.

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).

Somatic Overgrowth Predisposes to Seizures in Autism Spectrum Disorders

Background Comorbidity of Autism Spectrum Disorders with seizures or abnormal EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a starting point to identify distinct populations within the clinical complexity of the autistic spectrum. In this study, we tried to assess whether distinct subgroups, having distinctive clinical hallmarks, emerge from this comorbid condition. Methods Two-hundred and six individuals with idiopathic Autism Spectrum Disorders were subgrouped into three experimental classes depending on the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical and auxological parameters were investigated to identify differences among groups and features which increase the risk of seizures. Our statistical analyses used ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze continuous and categorical variables. A correspondence analysis was also used to decompose significant Chi-squared and reduce variables dimensions. Results The high percentage of children with seizures (28.2% of our whole cohort) and EEG abnormalities (64.1%) confirmed that the prevalence of epilepsy in Autism Spectrum Disorders exceeds that of the general population. Seizures were associated with severe intellectual disability, and not with autism severity. Interestingly, tall stature (without macrocephaly) was significantly associated with EEG abnormalities or later onset seizures. However, isolated macrocephaly was equally distributed among groups or associated with early onset seizures when accompanied by tall stature. Conclusions Tall stature seems to be a phenotypic “biomarker” of susceptibility to EEG abnormalities or late epilepsy in Autism Spectrum Disorders and, when concurring with macrocephaly, predisposes to early onset seizures. Growth pattern might act as an endophenotypic marker in Autism-Epilepsy comorbidity, delineating distinct pathophysiological subtypes and addressing personalized diagnostic work-up and therapeutic approaches.

Application of the Repetitive Behavior Scale-Revised - Italian version - in preschoolers with autism spectrum disorder

Restricted repetitive and stereotyped patterns of behavior, interests, and activities (RRB) are mandatory features for a diagnosis of Autism Spectrum Disorder (ASD) according to the Diagnostic and Statistical Manual of mental disorders-fifth edition (DSM-5). Despite the strong diagnostic role of RRB, their expressiveness and their relationship with other clinical/demographic features in ASD is not fully elucidated. The Italian version of the Repetitive Behavior Scale-Revised (RBS-R) was applied to a relatively large sample of preschool-aged children with ASD who underwent a comprehensive clinical assessment. The relationship between RRB and sex, age, non-verbal IQ, autism severity, as well as the diagnostic accuracy of the RBS-R were explored. Stereotyped and Ritualistic/Sameness behaviors were the most common RRB in preschoolers with ASD, without widespread differences between males and females. No significant correlations between RRB and chronological age, or non-verbal IQ were detected. The expressiveness of ritualistic/sameness behaviors positively correlated with autism severity, assessed through the Calibrated Severity Score (CSS) derived from the Autism Diagnostic Observation Schedule (ADOS). Receiver Operator Characteristic (ROC) analysis showed high diagnostic accuracy using the Global Rating Score, which represents the judgment of the parents of as the RRB affect the childs life. However, while the Global Rating Score performed well, the remaining subscales did not. This investigation extends the limited research on early pattern and associated features of RRB in young children with ASD. The use of the RBS-R may increase the knowledge of the RRB complexity and variability and in turn improve the diagnostic and therapeutic procedures within the autistic spectrum.