In addition, cytokines can contribute to HPA axis hyperactivity, and affect the serotonergic, dopaminergic, glutamatergic and monoamonergic systems, contributing to MDD.43 Accordingly, pro-inflammatory cytokines stimulate glucocorticoid release by acting at all three levels of the HPA axis: at the paraventricular nucleus level, they stimulate the release of corticotropin-releasing hormone (CRH) level; at the pituitary level, they stimulate the release of adrenocorticotropin; and at the adrenal glands, they stimulate the release of glucocorticoids. This evidence concerns the gene CRH and major depressive disorder.