IRS1 and Insulin resistance: For example, insulin receptor substrate -1 (IRS-1), a protein associated with insulin resistance, was increased in neuron-delivered EVs from patients with MDD, thus indicating the relationship between insulin resistance in the CNS and clinical symptoms such as depressive feelings, suicide and anhedonia.32 However, among various components in EVs, miRNA has been adequately explored and seems to be the most promising biomarker.