Anxiety Disorders and Sensory Over-Responsivity in Children with Autism Spectrum Disorders: Is There a Causal Relationship?

Anxiety disorders and sensory over-responsivity (SOR) are common in children with autism spectrum disorders (ASD), and there is evidence for an association between these two conditions. Currently, it is unclear what causal mechanisms may exist between SOR and anxiety. We propose three possible theories to explain the association between anxiety and SOR: (a) SOR is caused by anxiety; (b) Anxiety is caused by SOR; or (c) SOR and anxiety are causally unrelated but are associated through a common risk factor or diagnostic overlap. In this paper, we examine support for each theory in the existing anxiety, autism, and neuroscience literature, and discuss how each theory informs choice of interventions and implications for future studies

A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation

International audienceThe guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation. Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and contains a non-synonymous polymorphism in the major candidate gene Vav1. To formally demonstrate the causal implication of this polymorphism, we generated a knock-in mouse bearing this polymorphism (Vav1(R63W)). Using this model, we show that Vav1(R63W) mice display reduced susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by MOG35-55 peptide immunization. This is associated with a lower production of effector cytokines (IFN-gamma, IL-17 and GM-CSF) by autoreactive CD4 T cells. Despite increased proportion of Foxp3+ regulatory T cells in Vav1(R63W) mice, we show that this lowered cytokine production is intrinsic to effector CD4 T cells and that Treg depletion has no impact on EAE development. Finally, we provide a mechanism for the above phenotype by showing that the Vav1(R63W) variant has normal enzymatic activity but reduced adaptor functions. Together, these data highlight the importance of Vav1 adaptor functions in the production of inflammatory cytokines by effector T cells and in the susceptibility to neuroinflammation