behavior33,35. Future molecular studies must investigate how downregulation of synaptic gene expression could lead to observed hyperactivity in the OFC and striatum of OCD patients. In the OFC, hyperactivity may be driven through a decrease in expression patterns representative of inhibitory interneurons (Fig. 3B), which regulate excitatory/inhibitory balance. In the striatum, downregulation of synaptic gene expression is likely related to a decrease in the expression profile of medium spiny neurons (Fig. 3A, C, D), which are the primary recipients of cortico-striatal glutamatergic input. It will be of interest to determine whether alterations in cell type expression profiles are due to a change in the absolute number of that cell type in OCD subjects, a shift in an individual cell’s expression profile (e.g., a decrease in the number of synapses), or compensatory changes due to alterations in other cell types.
