Association of X-box binding protein 1 ( XBP1) genotype with morning cortisol and 1-year clinical course after a major depressive episode.
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 (-116C-->G) 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 hypothalamic-pituitary-adrenocortical and cellular stress pathways involving the XBP1 gene may be involved in the pathophysiology of major depressive disorder. These relationships merit further study.
Grunebaum
Michael F
MF
Department of Psychiatry, Columbia University, New York, NY 10032, USA. mfg14@columbia.edu
Galfalvy
Hanga C
HC
Huang
Yung-yu
YY
Cooper
Thomas B
TB
Burke
Ainsley K
AK
Agnello
Melissa
M
Oquendo
Maria A
MA
Mann
J John
JJ
D000328:Adult; D002940:Circadian Rhythm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003865:Major Depressive Disorder / Q000097:blood* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011863:Radioimmunoassay / Q000379:methods; D000071701:Regulatory Factor X Transcription Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D006854:Hydrocortisone