Abstract:Bipolar disorder (BD) is a major subtype of mood disorders, and major depressive disorder (MDD), also called unipolar depression, is another important subtype of mood disorders. BD is characterized by cyclical alterations of depressive and maniac symptoms. Both BD and MDD are serious diseases which greatly affect human mental health. Dysfunction of stress response systems including the hypothalamic-pituitary-adrenal (HPA) axis has been confirmed to be an important pathogenesis of mood disorders. However, there is still a lack of systematic studies on HPA axis activity in BD patients. Most of the existing studies only focus on the changes in the levels of plasma cortisol and salivary cortisol, with a great difference in results between these studies; however, dexamethasone/corticotropin-releasing hormone test has achieved relatively consistent results from the studies and has shown a significant reduction in cortisol inhibition, suggesting an abnormal negative feedback regulation function of the HPA axis in BD patients. Glucocorticoid receptor (GR) and FK 506 binding protein 51 (FKBP51), a member of the immunophilin family, are two important molecules involved in the negative feedback regulation of the HPA axis. On the one hand, single nucleotide polymorphism of the GR gene is thought to be associated with the onset of BD; on the other hand, childhood trauma may increase the risk of BD, possibly by affecting the sensitivity of the HPA axis, and GR and FKBP51 are involved in the regulation of the sensitivity of the HPA axis during this process. This article reviews the recent studies on abnormal HPA axis activity in BD patients and disorder in negative feedback regulation of the HPA axis caused by GR and FKBP51, in order to provide new ideas for research on the pathogenesis of BD associated with stress response.
