TNF and schizophrenia: If schizophrenia patients do have a more permeable BBB, allowing TNF-α and LPS to pass through the BBB and act upon neurons, the combination of increased LPS-induced IP3 production and TNF-α induced IP3R upregulation, could combine to result in much higher levels of Ca2+ being released from the ER in neurons, resulting in a large amount of excitatory glutamate release into the synaptic cleft (Figure 6).