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As explained later, these components can cross-talk with other pathways such as the MAPK/ERK1/2 (mitogen activated protein kinase/extracellular signal-regulated kinase 1/2) and PI3/Akt (phosphoinositide 3-kinase/protein kinase B) signaling cascades causing changes in gene expression and modifying cell metabolism and proliferation (47)

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and iii) increased oxidative stress, due to the putative role of thiamine in prostaglandin expression, decreased lipid peroxidation as well as expression of nitric oxide synthase (143, 144), and its involvement as a cofactor for TKT in the PPP, master regulator of NADPH homeostasis

Clinical manifestations include negative symptoms, such as affective flattening, social disengagement, and avolition, as well as positive symptoms, including hallucinations and delusions