Abstract

To evaluate the CRH overdrive hypothesis in depression, we will evaluate two alternative hypotheses explaining the HPA axis abnormalities in depression. Only one of these two hypotheses can be valid. These hypotheses are:1. In depression there is increased central CRH secretion, including increased PVN CRH secretion, that is dampened by glucocorticoid negative feedback. When ACTH is examined in the absence of negative feedback (open loop system), produced by metyrapone blockade of cortisol production, there will be increased ACTH secretion throughout the day. OR 2. In depression there is dysregulation of circadian driven CRH secretion accompanied by alterations in the circadian rhythm of ACTH and cortisol secretion. A failure of the inhibitory circuits to restrain HPA axis secretion occurs at a specific circadian phase, the evening.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000042-39
Application #
6297123
Study Section
Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
39
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Robarge, Jason D; Desta, Zereunesay; Nguyen, Anne T et al. (2017) Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer. Breast Cancer Res Treat 161:453-461
Crane, Natania A; Jenkins, Lisanne M; Bhaumik, Runa et al. (2017) Multidimensional prediction of treatment response to antidepressants with cognitive control and functional MRI. Brain 140:472-486
Hertz, Daniel L; Speth, Kelly A; Kidwell, Kelley M et al. (2017) Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients. Breast Cancer Res Treat 165:659-668
Hertz, D L; Kidwell, K M; Seewald, N J et al. (2017) Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer. Pharmacogenomics J 17:521-527
Kadakia, Kunal C; Kidwell, Kelley M; Seewald, Nicholas J et al. (2017) Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors. Breast Cancer Res Treat 164:411-419
Spengler, Erin K; Kleiner, David E; Fontana, Robert J (2017) Vemurafenib-induced granulomatous hepatitis. Hepatology 65:745-748
Heidemann, Lauren; Law, James; Fontana, Robert J (2017) A Text Searching Tool to Identify Patients with Idiosyncratic Drug-Induced Liver Injury. Dig Dis Sci 62:615-625
Kadakia, Kunal C; Snyder, Claire F; Kidwell, Kelley M et al. (2016) Patient-Reported Outcomes and Early Discontinuation in Aromatase Inhibitor-Treated Postmenopausal Women With Early Stage Breast Cancer. Oncologist 21:539-46
Ricker, Charité; Culver, Julie O; Lowstuter, Katrina et al. (2016) Increased yield of actionable mutations using multi-gene panels to assess hereditary cancer susceptibility in an ethnically diverse clinical cohort. Cancer Genet 209:130-7
Law, Ian H; Alam, Osman; Bove, Edward L et al. (2016) Follow-Up of a Prospective Surgical Strategy to Prevent Intra-Atrial Reentrant Tachycardia After the Fontan Operation. Circ Arrhythm Electrophysiol 9:

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