Elizabeth A. Young, M.D.
Research Professor, M.D.
Professor, Department of Psychiatry

1044 MBNI Building
205 Zina Pitcher Place
Ann Arbor , MI 48109-0720

eayoung@umich.edu

(734) 936-2087

Current Research Interests:

My research focuses on depression and Hypothalamic-pituitary adrenal (HPA) axis abnormalities in persons with major depression. I have conducted a number of HPA axis studies in depression, which include studies on dexamethasone suppression of -endorphin secretion in depression, oCRF infusion studies in depression, fast feedback effects of cortisol in depressed patients, effects of repeated ECT (a "stress") on HPA axis regulation in human, and the effects of evening metyrapone (removal of negative feedback) on HPA axis activation in depression.

In addition to clinical studies, I have conducted basic science studies on chronic stress that were designed to understand some of the regulatory, adaptive changes that the HPA axis undergoes with chronic stress. These studies give us a baseline to compare to the regulatory abnormalities in depression. My research focus has been expanded to the interaction of the HPA axis with the gonadal axis and abnormalities in reproductive hormones in depressed women. Again as both a clinical and basic science researcher, we examine the multiple levels at which these interactions may occur ranging from actions of gonadal steroids on glucocorticoid receptors in animal models to sex differences in HPA axis regulation in humans, particularly in depression, a disorder associated with stress and activation of the HPA axis.

Work has focused upon how gonadal steroids modulate stress responsiveness, and the implications of the loss of gonadal steroids, at menopause, on the neurobiology of stress and brain functioning. We have also examined the roles of mineralocorticoid receptors (MR) and glucocorticoid receptors in depression by use of an acute MR receptor antagonist, spironolactone. (Fig1). These studies demonstrated increased activity of MR in patients with depression which would lead to a distrubance of the MR:GR balance.

Recent studies also examined the role of comorbid anxiety disorders on the HPA axis and we have shown a much greater response to a public speaking task stressor (TSST, Fig 2) in patients with both depression and anxiety disorders. We have also examined reproductive hormone abnormalities in women with major depression and found significantly lower estradiol and changes in leutenizing hormone (LH) rhythms in depression. Fig 3 shows that depressed women (MDD) have 2 frequencies of LH rhythms during the follicular phase and reduced power in the predominant frequency seen in normal subjects. Ongoing work is focused on determining whether excess activation of the HPA axis in depression is circadian phase specific or occurs around the clock. Collaborations with other investigators include studies on neuroimaging and response to treatment.

Fig. 1

Fig. 2

Fig. 3

Selected Publications:

Young EA,. López , JF Murphy-Weinberg V, Watson S, Akil H Mineralocorticoid Receptor Function in Major Depression, Archives of General Psychiatry, 60:24-28, 2003

Young EA and Breslau N Cortisol and Catecholamines in Posttraumatic Stress Disorder: A Community Study, Archives General Psychiatry, 61:394-401, 2004

Young EA, Abelson JL and Cameron OG. Effect of Comorbid Anxiety Disorders on the HPA Axis Response to a Social Stressor in Major Depression, Biological Psychiatry , ;56:113-20, 2004.

Young EA, Midgley AR, Carlson NE, Brown MB. Alteration in the Hypothalamic-Pituitary-Ovarian axis in depressed women. Archives of General Psychiatry, 57:1157-1162, 2000

Grambsch P, Young EA and Meller WH. Pulsatile Leutininzing Hormone Disruption in Depression, Psychoneuroendocrinology, 29:825-9, 2004