There is increasing evidence from case reports that synesthesia is more common in individuals with autism spectrum conditions (ASC). Further, genes related to synesthesia have also been found to be linked to ASC and, similar to synaesthetes, individuals with ASC show altered brain connectivity and unusual brain activation during sensory processing. However, up to now a systematic investigation of whether synesthesia is more common in ASC patients is missing. The aim of the current pilot study was to test this hypothesis by investigating a group of patients diagnosed with Asperger Syndrome (AS) using questionnaires and standard consistency tests in order to classify them as grapheme-color synaesthetes. The results indicate that there are indeed many more grapheme-color synaesthetes among AS patients. This finding is discussed in relation to different theories regarding the development of synesthesia as well as altered sensory processing in autism.

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CASK-related disorders are genetically defined neurodevelopmental syndromes. There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carriers. One male case with autism spectrum disorder carried a novel splice-site mutation and a female case with intellectual disability carried an intragenic tandem duplication. We show reduction of CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of genes involved in presynaptic development and of CASK protein interactors. Furthermore, CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory–inhibitory (E/I) balance in developing neural circuitries. Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in the brain. Our data show that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments for CASK-related disorders.

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Deficits in facial mimicry have been widely reported in autism. Some studies have suggested that these deficits are restricted to spontaneous mimicry and do not extend to volitional mimicry. We bridge these apparently inconsistent observations by testing the impact of reward value on neural indices of mimicry and how autistic traits modulate this impact. Neutral faces were conditioned with high and low reward. Subsequently, functional connectivity between the ventral striatum (VS) and inferior frontal gyrus (IFG) was measured while neurotypical adults (n = 30) watched happy expressions made by these conditioned faces. We found greater VS–IFG connectivity in response to high reward vs low reward happy faces. This difference was negatively proportional to autistic traits, suggesting that reduced spontaneous mimicry of social stimuli seen in autism, may be related to a failure in the modulation of the mirror system by the reward system rather than a circumscribed deficit in the mirror system.

Autism spectrum disorder (ASD) has been found to be associated with alterations in resting state (RS) functional connectivity, including areas forming the default mode network (DMN) and salience network (SN). However, insufficient control for confounding genetic and environmental influences and other methodological issues limit the generalizability of previous findings. Moreover, it has been hypothesized that ASD might be marked by early hyper-connectivity followed by later hypo-connectivity. To date, only a few studies have explicitly tested age-related influences on RS connectivity alterations in ASD. Using a within-twin pair design (N = 150 twins; 8-23 years), we examined altered RS connectivity between core regions of the DMN and SN in relation to autistic trait severity and age in a sample of monozygotic (MZ) and dizygotic (DZ) twins showing typical development, ASD or other neurodevelopmental conditions. Connectivity between core regions of the SN was stronger in twins with higher autistic traits compared to their co-twins. This effect was significant both in the total sample and in MZ twins alone, highlighting the effect of non-shared environmental factors on the link between SN-connectivity and autistic traits. While this link was strongest in children, we did not identify differences between age groups for the SN. In contrast, connectivity between core hubs of the DMN was negatively correlated with autistic traits in adolescents and showed a similar trend in adults but not in children. The results support hypotheses of age-dependent altered RS connectivity in ASD, making altered SN and DMN connectivity promising candidate biomarkers for ASD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.160 INTRODUCTION Altered patterns of brain connectivity have been suggested as a key neurobiological correlate of the behavioral characteristics of autism spectrum disorder (ASD). However, as findings are inconsistent, the precise brain connectivity characteristics of ASD remain unclear. A large number of resting-state (RS) functional magnetic resonance imaging (MRI) brain connectivity studies have shown a complex pattern of both hypo-and hyper-connectivity in ASD.1-3 Notably, a large multi-site classification study including ASD and typically developing individuals (N = 252, 6-36 years) showed that of the top 100 biomarkers of brain connectivity achieving together 90.8% accuracy, 45% were related to hyperconnectivity and the remaining 55% to hypo-connectivity. 4 It is likely that the observed inconsistencies in classical brain connectivity investigations are limited by methodological issues, such as insufficient control for head motion or the inclusion of global signal regression which can modulate or even invert the direction of functional connectivity differences. [5][6][7] Moreover, gender has recently been shown to modulate the direction of connectivity differences in ASD. 8 In contrast, another study found default mode network (DMN) hypo-connectivity in both genders.

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