Association of X-box binding protein 1 (XBP1) genotype with morning cortisol and 1-year clinical course after a major depressive episode

Abstract

Brain diseases including Alzheimer's and Parkinson's involve the cellular unfolded protein (UPR) stress response. Psychiatric illnesses such as depressive disorders are thought to involve brain stress-response pathways. The XBP1 gene encodes a key transcription factor in the UPR stress response and therefore could be involved in the pathophysiology of depressive disorders. A functional polymorphism (116CG) in the XBP1 promoter was linked in some studies to bipolar disorder. Among 132 adults (mean age 39 yr) who presented with a major depressive episode, this polymorphism was found to be associated with a worse course during 1-yr prospective follow-up. In a subgroup (n=22), the polymorphism was associated with higher plasma levels of the stress hormone cortisol. The results suggest that hypothalamicpituitaryadrenocortical and cellular stress pathways involving the XBP1 gene may be involved in the pathophysiology of major depressive disorder. These relationships merit further study. Copyright © 2009 CINP.