The strong association between increased C4A expression with schizophrenia (Sekar et al., 2016), the involvement of classical complement cascade in synapse elimination (Stevens et al., 2007; Schafer et al., 2012; Bialas and Stevens, 2013; Sekar et al., 2016; Comer et al., 2019), and the decreased brain connectivity and sociability in mice overexpressing C4 in the prefrontal cortex (Comer et al., 2019) strongly suggest that enhanced complement-mediated synaptic pruning contributes directly to reduction in cortical gray matter thickness and to schizophrenia pathogenesis. Here, C4A is linked to schizophrenia.