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

Laura M. Holsen, Sarah B. Spaeth, Jong-Hwan Lee, Lauren A. Ogden, Anne Klibanski, Susan Whitfield-Gabrieli, Jill M. Goldstein

Research output: Contribution to journalArticle

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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. 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 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.

Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalJournal of Affective Disorders
Volume131
Issue number1-3
DOIs
Publication statusPublished - 2011 Jun 1
Externally publishedYes

Fingerprint

Major Depressive Disorder
Depression
Gyrus Cinguli
Amygdala
Prefrontal Cortex
Hypothalamus
Progesterone
Gonadal Hormones
Estradiol
Hippocampus
Magnetic Resonance Imaging
Oxygen
Follicular Phase
Brain
Arousal
Serum
Reproducibility of Results
Sex Characteristics
Sample Size
Testosterone

Keywords

  • Depression
  • fMRI
  • Hormones
  • HPG
  • Stress
  • Women's mental health

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Holsen, L. M., Spaeth, S. B., Lee, J-H., Ogden, L. A., Klibanski, A., Whitfield-Gabrieli, S., & Goldstein, J. M. (2011). Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression. Journal of Affective Disorders, 131(1-3), 379-387. https://doi.org/10.1016/j.jad.2010.11.024

Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression. / Holsen, Laura M.; Spaeth, Sarah B.; Lee, Jong-Hwan; Ogden, Lauren A.; Klibanski, Anne; Whitfield-Gabrieli, Susan; Goldstein, Jill M.

In: Journal of Affective Disorders, Vol. 131, No. 1-3, 01.06.2011, p. 379-387.

Research output: Contribution to journalArticle

Holsen, LM, Spaeth, SB, Lee, J-H, Ogden, LA, Klibanski, A, Whitfield-Gabrieli, S & Goldstein, JM 2011, 'Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression', Journal of Affective Disorders, vol. 131, no. 1-3, pp. 379-387. https://doi.org/10.1016/j.jad.2010.11.024
Holsen, Laura M. ; Spaeth, Sarah B. ; Lee, Jong-Hwan ; Ogden, Lauren A. ; Klibanski, Anne ; Whitfield-Gabrieli, Susan ; Goldstein, Jill M. / Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression. In: Journal of Affective Disorders. 2011 ; Vol. 131, No. 1-3. pp. 379-387.
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