Neurobiological Predictors of Stress-Related Disorders

压力相关疾病的神经生物学预测因素

• 批准号: 6608586
• 负责人: Israel Liberzon
• 金额: $ 31.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-05 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6608586
• 关键词: biomarker; cardiovascular surgery; catecholamines; clinical research; comorbidity; corticosteroid receptors; depression; dexamethasone; disease /disorder proneness /risk; human morbidity; human subject; hypercortisolism; hypothalamic pituitary adrenal axis; injury /disease stressor; longitudinal human study; neurobiology; neuroendocrine system; patient oriented research; postoperative state; posttraumatic stress disorder; preoperative state; social support network; stress

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：与压力相关的精神疾病，尤其是术后抑郁症，构成了重大挑战。抑郁，焦虑和创伤后应激障碍（PTSD）经常在各种压力源，例如手术，严重疾病，汽车事故和自然灾害以及脆弱性因素之后发展。下丘脑 - 垂体 - 肾上腺（HPA）异常的独特特征，在抑郁症和PTSD中已经建立了良好疾病，仍有待确定。只有在可预测的压力事件之前对标记物进行的前瞻性研究将能够有效地解决这个问题，并阐明神经内分泌对压力对压力的作用。研究经历可预测的压力事件（例如大手术）的受试者中敏感性的候选标记，不仅对于研究后抑郁症的研究，而且对于一般与压力相关的疾病的研究也很重要。我们的假设是，术后抑郁症在与特定的病前风险因素一致的神经内分泌功能前改变的患者发生术后抑郁症。我们的试点调查结果表明，主要的腹部手术构成了可预测的压力事件，导致术后患者亚组的从头抑郁症。因此，我们将检验以下假设：HPA轴和儿茶酚胺能系统的预压标记将预测腹部手术可预测的应激后抑郁症的发展。我们预测高皮层血症和DST非抑制作用将预测抑郁症。将对2例接受选修内血管内或腹部主动脉症的患者组成的动脉瘤或闭塞性疾病，并将研究70名“对照”患者进行保守治疗的主动脉疾病患者（4组）。手术患者将在术前进行评估，并在术后进行三次（3、9和18 mo。），以记录术前和术后神经内分泌功能和精神病发病率。将评估对照患者以确定精神异常自发发作的频率。使用混合模型回归，我们将研究心理和神经内分泌异常在术后抑郁症中的作用，并确定特定因素（神经内分泌测量，精神症状和诊断）的稳定性以及它们是否可靠地预测术后合并症的发展。我们还将确定手术后终止神经内分泌应激反应的能力或对地塞米松的响应能够预测结果，以及这是否与预压力异常有关。识别脆弱性预压标记显然对我们对与压力相关的功能障碍的理解，精神疾病的病理生理学有了深远的影响。