The aim of this paper is to outline how excessive levels of PICs, notably TNF-α, ROS, and RNS, can lead to mitochondrial dysfunction and compromised bioenergetics in PD, MS, CFS, depression, bipolar disorder, schizophrenia and autism, by inhibiting the electron transport chain (ETC), the tricarboxylic acid cycle, and fatty acid oxidation, adversely affecting the activity and structure of structural and regulatory proteins and the integrity of essential functional lipid membranes. Here, TNF is linked to schizophrenia.