Central and peripheral causes of brain insulin resistance in schizophrenia

Multiple interconnected pathways may underlie impaired brain insulin signaling in schizophrenia. These include both central/neurobiological mechanisms (i.e., neuroinflammation, mitochondrial dysfunction, Akt pathway dysfunction, oxidative stress) and peripheral mechanisms (i.e., visceral adiposity, increased insulin release, chronic stress, and inflammation). Additionally, antipsychotic medications exacerbate both peripheral and central mechanisms, contributing to increased appetite and weight gain, increased insulin release, increased hepatic glucose production, and decreased glucose uptake by skeletal muscle.