Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression

JOURNAL OF AFFECTIVE DISORDERS

卷:131

Article

Holsen, Laura M.^2,5  Spaeth, Sarah B.^2,5  Lee, Jong-Hwan³  Ogden, Lauren A.^2,5  Klibanski, Anne⁴  Whitfield-Gabrieli, Susan^5,6  Goldstein, Jill M.^1,2,5 

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Womens Hlth, Dept Psychiat,Connors Ctr Womens Hlth & Gender Bi, Boston, MA 02120 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02120 USA

[3] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02120 USA

[4] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02120 USA

[5] MIT, Athinoula Martinos Ctr Biomed Imaging, Cambridge, MA 02139 USA

[6] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

关键词: Depression;    Stress;    Hormones;    fMRI;    HPG;    Women's mental health;   

DOI  :  10.1016/j.jad.2010.11.024

来源: Elsevier

【 摘 要 】

Background: Women have approximately twice the risk of major depressive disorder (MDD) than men, yet this difference remains largely unexplained. Previous MDD research suggests high rates of endocrine dysfunction, which may be related to deficits in brain activity in stress response circuitry (hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC)]. This functional magnetic resonance imaging (fMRI) study investigated the relationship between hypothalamic-pituitary-gonadal (HPG)-axis hormones and stress response circuitry dysfunction in MOD in women. Methods: During the late follicular/midcycle phase of the menstrual cycle, female participants (10 with extensive histories of MDD, in remission, 10 healthy controls) were scanned while viewing negative and neutral arousal pictures. Group differences in blood oxygen-level dependent (BOLD) signal changes were analyzed using SPM2. Baseline gonadal hormones included estradiol, progesterone, and testosterone. Results: fMRI results showed greater BOLD signal intensity changes in controls versus MOD in hypothalamus, amygdala, hippocampus, OFC, ACC, and subgenual ACC, findings unrelated to medication status. MOD women had a lower serum estradiol and higher serum progesterone compared to controls. Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone. Limitations: Generalizability of our findings is limited by small sample size and restriction to females, although this did not affect the internal validity of the results. Conclusions: Hypoactivation of the stress response circuitry in MOD women is associated with dysregulation of the HPG-axis. Associations between brain activity deficits and hormonal disruption in MDD may ultimately contribute to understanding sex differences in MOD. (C) 2010 Elsevier B.V. All rights reserved.

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