title: A common and functional mineralocorticoid receptor haplotype enhances optimism and protects against depression in females.
abstract: Mineralocorticoid (MR) and glucocorticoid receptors (GR) are abundantly expressed in the limbic brain and mediate cortisol effects on the stress-response and behavioral adaptation. Dysregulation of the stress response impairs adaptation and is a risk factor for depression, which is twice as abundant in women than in men. Because of the importance of MR for appraisal processes underlying the initial phase of the stress response we investigated whether specific MR haplotypes were associated with personality traits that predict the risk of depression. We discovered a common gene variant (haplotype 2, frequency ∼0.38) resulting in enhanced MR activity. Haplotype 2 was associated with heightened dispositional optimism in study 1 and with less hopelessness and rumination in study 2. Using data from a large genome-wide association study we then established that haplotype 2 was associated with a lower risk of depression. Interestingly, all effects were restricted to women. We propose that common functional MR haplotypes are important determinants of inter-individual variability in resilience to depression in women by differentially mediating cortisol effects on the stress system.
authors: Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden, The Netherlands.
authors: M D
authors: MD
authors: Klok
authors: E J
authors: EJ
authors: Giltay
authors: A J W
authors: AJ
authors: Van der Does
authors: J M
authors: JM
authors: Geleijnse
authors: N
authors: N
authors: Antypa
authors: B W J H
authors: BW
authors: Penninx
authors: E J C
authors: EJ
authors: de Geus
authors: G
authors: G
authors: Willemsen
authors: D I
authors: DI
authors: Boomsma
authors: N
authors: N
authors: van Leeuwen
authors: F G
authors: FG
authors: Zitman
authors: E R
authors: ER
authors: de Kloet
authors: R H
authors: RH
authors: DeRijk
mesh_terms: D000328:Adult; D000368:Aged; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010551:Personality / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011569:Psychiatric Status Rating Scales; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D012306:Risk; D012737:Sex Factors; D055815:Young Adult
chemical_list: D018161:Receptors, Mineralocorticoid