title: Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression.
abstract: 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 MDD 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 MDD in hypothalamus, amygdala, hippocampus, OFC, ACC, and subgenual ACC, findings unrelated to medication status. MDD 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.
  
  
  CONCLUSIONS
  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 MDD 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 MDD.
authors.affiliation: Harvard Medical School, Department of Psychiatry, Brigham and Women's Hospital, Connors Center for Women's Health and Gender Biology, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Holsen
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Spaeth
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Ogden
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.forename: Jill M
authors.initials: JM
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000503:physiopathology*; D004958:Estradiol / Q000097:blood; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D011374:Progesterone / Q000097:blood; D013315:Stress, Psychological / Q000503:physiopathology; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D011374:Progesterone; D004958:Estradiol