MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Holsen, 2011 PubMed
Full Info	Holsen, L.M., Spaeth, S.B., Lee, J.H., Ogden, L.A., Klibanski, A., Whitfield-Gabrieli, S. and Goldstein, J.M. (2011) Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression. J Affect Disord, 131, 379-387.

Study

Hypothesis or 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.
Sample Information	female participants (10 with extensive histories of MDD, in remission, 10 healthy controls)
Method Detail	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.
Method Keywords	functional magnetic resonance imaging (fMRI); blood analysis
Result	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	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.
Remark	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.

Relationships reported by Holsen, 2011

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
subgenual anterior cingulate (subgenual anterior cingulate cortex (ACC))	brain morphology and function	Progesterone (progesterone)	molecule		Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.	Positive
Orbitofrontal cortex (orbitofrontal cortex (OFC))	brain morphology and function	Progesterone (progesterone)	molecule		Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.	Positive
MDD	syndrome	Progesterone (progesterone)	molecule		MDD women had a lower serum estradiol and higher serum progesterone compared to controls.	Positive
MDD	syndrome	Estradiol (estradiol)	molecule		MDD women had a lower serum estradiol and higher serum progesterone compared to controls.	Positive
MDD	syndrome	Hippocampus (hippocampus)	brain morphology and function		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.	Positive
MDD	syndrome	Hypothalamus (hypothalamus)	brain morphology and function		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.	Positive
MDD	syndrome	Amygdala (amygdala)	brain morphology and function		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.	Positive
MDD	syndrome	Anterior cingulate cortex (anterior cingulate cortex (ACC))	brain morphology and function		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.	Positive
Stress (stress)	environment	Hypothalamic-pituitary-gonadal axis (hypothalamic-pituitary-gonadal (HPG)-axis)	neurobiological system		Hypoactivation of the stress response circuitry in MDD women is associated with dysregulation of the HPG-axis.	Positive
MDD	syndrome	Hypothalamic-pituitary-gonadal axis (hypothalamic-pituitary-gonadal (HPG)-axis)	neurobiological system		Hypoactivation of the stress response circuitry in MDD women is associated with dysregulation of the HPG-axis.	Positive
MDD	syndrome	Orbitofrontal cortex (orbitofrontal cortex (OFC))	brain morphology and function		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.	Positive
MDD	syndrome	subgenual anterior cingulate (subgenual anterior cingulate cortex (ACC))	brain morphology and function		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.	Positive
subgenual anterior cingulate (subgenual anterior cingulate cortex (ACC))	brain morphology and function	Estradiol (estradiol)	molecule		Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.	Positive
Hypothalamus (hypothalamus)	brain morphology and function	Progesterone (progesterone)	molecule		Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.	Positive
Hypothalamus (hypothalamus)	brain morphology and function	Estradiol (estradiol)	molecule		Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.	Positive
Orbitofrontal cortex (orbitofrontal cortex (OFC))	brain morphology and function	Estradiol (estradiol)	molecule		Hypoactivations in hypothalamus, subgenual ACC, amygdala and OFC in MDD were associated with low estradiol and high progesterone.	Positive