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A plethora of neuroimaging studies have focused on the discovery of potential neuroendophenotypes useful to understand the etiopathogenesis of autism and predict treatment response. Social robotics has recently been proposed as an effective tool to strengthen the current treatments in children with autism. However, the high clinical heterogeneity characterizing this disorder might interfere with behavioral effects. Neuroimaging is set to overcome these limitations by capturing the level of heterogeneity. Here, we provide a preliminary evaluation of the neural basis of social robotics and how extracting neural hallmarks useful to design more effective behavioral applications. Despite the endophenotype-oriented neuroimaging research approach is in its relative infancy, this preliminary evidence encourages innovation to address its current limitations.

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism. © 2015 Macmillan Publishers Limited. 20 3 369 376 Cited By :73; Export Date: 17 July 2017

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Assistive technology is a generic system that is used to increase, help or improve the functional capabilities of people with disability. Recently, its employment has generated innovative solutions also in the field of Autism Spectrum Disorder (ASD), where it is extremely challenging to obtain feedback or to extract meaningful data. In this work, a study about the possibility to understand the visual exploration in children with ASD is presented. In order to obtain an automatic evaluation, an algorithm for free gaze estimation is employed. The proposed gaze estimation method can work without constrains nor using additional hardware, IR light sources or other intrusive methods. Furthermore, no initial calibration is required. These relaxations of the constraints makes the technique particularly suitable to be used in the critical context of autism, where the child is certainly not inclined to employ invasive devices. In particular, the technique is used in a scenario where a closet containing specific toys, that are neatly disposed from the therapist, is opened to the child. After a brief environment exploration, the child will freely choose the desired toy that will be subsequently used during therapy. The video acquisition have been accomplished by a Microsoft Kinect sensor hidden into the closet in order to obtain both RGB and depth images, that can be processed by the estimation algorithm, therefore computing gaze tracking by intersection with data coming from the well-known initial disposition of toys. The system has been tested with children with ASD, allowing to understand their choices and preferences, letting to optimize the toy disposition for cognitive-behavioural therapy.

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD., Author Summary Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While mutations in several genes have been identified in patients with ASD, little is known about their effects on neuronal function and their interaction with other genetic variations. Using a combination of genetic and functional approaches, we identified novel SHANK2 mutations including a de novo loss of one copy of the SHANK2 gene in a patient with autism and several mutations observed in patients that reduced neuronal cell contacts in vitro. Further genomic analysis of three patients carrying de novo SHANK2 deletions identified additional rare genomic imbalances previously associated with neuropsychiatric disorders. Taken together, these results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.