C4A and schizophrenia: As for the mechanism by which C4 may contribute to schizophrenia, Yilmaz and colleagues investigated the role of C4A in a humanized mouse model of the disease and found that overexpressing C4A reduced cortical synapse density, increased microglial engulfment of synapses, and altered mouse behavior — overall indicating that uncontrolled C4A-mediated synaptic pruning is associated with abnormal brain circuits and behavior (223).