This grant provides support for an NIH Autism Center of Excellence (ACE). The overall goal of this ACE is to develop a translational program of research, from gene to behavior, around a clinically important, tractable, and understudied clinical problem in autism: the Insistence on Sameness (IS). At the biochemical level, research suggests that serotonin disturbances may contribute to IS. Rodent studies with serotonin inhibitors will provide a mechanistic understanding of the effects of serotonin receptor activation states. These animal studies will be complemented by a neurobehavioral and functional magnetic resonance imaging (fMRI) study of High IS patients treated with a serotonin inhibitor. The aim of this project is to seek a mechanistic understanding of behavioral features of IS in cognitive neuroscience and biochemical terms.