Major Histocompatibility Complex I in Brain Development and Schizophrenia

Although the etiology of schizophrenia (SZ) remains unknown, it is increasingly clear that immune dysregulation plays a central role. Genome-wide association studies reproducibly indicate an association of SZ with immune genes within the major histocompatibility complex (MHC). Moreover, environmental factors that increase risk for SZ, such as maternal infection, alter peripheral immune responses as well as the expression of immune molecules in the brain. MHC class I (MHCI) molecules might mediate both genetic and environmental contributions to SZ through direct effects on brain development in addition to mediating immunity. MHCI molecules are expressed on neurons in the central nervous system throughout development and into adulthood, where they regulate many aspects of brain development, including neurite outgrowth, synapse formation and function, long-term and homeostatic plasticity, and activity-dependent synaptic refinement. This review summarizes our current understanding of MHCI expression and function in the developing brain as well as its involvement in maternal immune activation, from the perspective of how these roles for MHCI molecules might contribute to the pathogenesis of SZ.