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

• Published in: Journal of affective disorders 2011-06, Vol.131 (1), p.379-387
• Main Authors: Holsen, Laura M, Spaeth, Sarah B, Lee, Jong-Hwan, Ogden, Lauren A, Klibanski, Anne, Whitfield-Gabrieli, Susan, Goldstein, Jill M
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Amygdala - metabolism; Amygdala - physiopathology; Biological and medical sciences; Brain - metabolism; Brain - physiopathology; Case-Control Studies; Cortex; Depression; Depressive Disorder, Major - blood; Depressive Disorder, Major - physiopathology; Depressive personality disorders; Dysfunction; Estradiol - blood; Female; fMRI; Frontal Lobe - metabolism; Frontal Lobe - physiopathology; Gyrus Cinguli - metabolism; Gyrus Cinguli - physiopathology; Hippocampus - metabolism; Hippocampus - physiopathology; Hormones; HPG; Humans; Hypothalamus - metabolism; Hypothalamus - physiopathology; Magnetic Resonance Imaging; Medical sciences; Mood disorders; Progesterone; Progesterone - blood; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Stress; Stress, Psychological - physiopathology; Testosterone - blood; Women; Women's mental health
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2010.11.024

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.