Stress-related psychiatric disorders in general, and post-operative depression in particular, constitute a major challenge. Depression, anxiety and post-traumatic stress disorder (PTSD) often develop after various stressors like surgery, serious illnesses, motor vehicle accidents, and natural disasters, and vulnerability factors are likely shared by these disorders. Distinct profiles of hypothalamo-pituitary - adrenal (HPA) abnormalities, are well-established in depression and PTSD, but those alterations which are pre-existing, those which are a response to stress/trauma, and those which are a component of the active illness, remain to be identified. Only prospective study of markers prior to a predictable stressful event will be able to address this question effectively and clarify the role of a neuroendocrine response to stress in the this process prospectively. Studying candidate markers of susceptibility in subjects who undergo a predictable stressful event, such as major surgery, will be important not only for study of post-operative depression but also for study of stress-related disorders in general. Our hypothesis is that postoperative depression develops in patients with pre-stress alteration of neuroendocrine function in concert with specific premorbid risk factors. Our pilot findings suggest that major abdominal surgery constitutes a predictable stressful event leading to a de novo depression in a subgroup of postoperative patients. Therefore, we will test the hypothesis that pre-stress markers of HPA axis and catecholaminergic system will predict the development of depressive disorder following predictable stress of abdominal surgery. We predict that hypercortisolemia and DST non-suppression will predict depression. A cohort of 2lO patients undergoing elective endovascular or abdominal aortic operation for aneurysmal or occlusive disease and 70 """"""""control"""""""" patients with aortic disease treated conservatively will be studied (4 groups). Surgical patients will be assessed preoperatively, and at three times postoperatively (3, 9, and 18 mo.) to document preoperative and postoperative neuroendocrine function and psychiatric morbidity. Control patients will be assessed to determine frequency of spontaneous onset of psychiatric abnormalities. Using mixed model regression, we will examine the role of psychological and neuroendocrine abnormalities in post-operative depression and determine the stability of specific factors (neuroendocrine measures, psychiatric symptoms and diagnoses) and whether they reliably predict the development of comorbid disorders postoperatively. We will also determine if the ability to terminate neuroendocrine stress response after surgery or in response to dexamethasone predicts outcome, and if this is linked to pre-stress abnormalities. Identification of pre-stress markers of vulnerability clearly has profound implications for our understanding of stress-related dysfunction, the pathophysiology of psychiatric disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063092-03
Application #
6764209
Study Section
Biobehavioral and Behavioral Processes 3 (BBBP)
Program Officer
Muehrer, Peter R
Project Start
2002-07-05
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$315,000
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
King, Anthony P; Abelson, James L; Gholami, Bardia et al. (2015) Presurgical Psychological and Neuroendocrine Predictors of Psychiatric Morbidity After Major Vascular Surgery: A Prospective Longitudinal Study. Psychosom Med 77:993-1005
Liberzon, Jonathan; Abelson, James L; King, Anthony et al. (2008) Naturalistic stress and cortisol response to awakening: adaptation to seafaring. Psychoneuroendocrinology 33:1023-6
Liberzon, Israel; Abelson, James L; Amdur, Richard L et al. (2006) Increased psychiatric morbidity after abdominal aortic surgery: risk factors for stress-related disorders. J Vasc Surg 43:929-34
McLean, Samuel A; Clauw, Daniel J; Abelson, James L et al. (2005) The development of persistent pain and psychological morbidity after motor vehicle collision: integrating the potential role of stress response systems into a biopsychosocial model. Psychosom Med 67:783-90