Golier Julia A, Schmeidler James, Yehuda Rachel
Departments of Psychiatry, James J. Peters VA Medical Center, Bronx, NY 10468, United States of America.
Psychoneuroendocrinology. 2009 Oct;34(9):1338-45. doi: 10.1016/j.psyneuen.2009.04.004. Epub 2009 May 14.
Gulf War deployment has been associated with a distinct neuroendocrine profile characterized by low 24h basal ACTH levels and enhanced cortisol and ACTH suppression to low-dose dexamethasone. The metyrapone stimulation test was performed to further characterize hypothalamic-pituitary activity in Gulf War veterans (GWV) and its relationship to unexplained medical symptoms and post-traumatic stress disorder (PTSD).
Eleven GWV without PTSD, 18 GWV with PTSD and 15 healthy subjects not exposed to the Gulf War theater (non-exposed) underwent the metyrapone stimulation test, which inhibits cortisol synthesis, impairs cortisol-mediated negative feedback inhibition and in turn increases levels of ACTH and 11-deoxycortisol, a cortisol precursor. These hormones were measured at baseline (7:00 a.m.) and at intervals (from 8:00 a.m. to 4:00 p.m.) following the administration of metyrapone 750mg orally at 7:05 a.m. and at 10:05 a.m.
There were group differences in the ACTH response despite similar cortisol and 11-deoxycortisol responses to metyrapone. GWV without PTSD had a significantly attenuated ACTH response compared to non-exposed subjects; GWV with PTSD had a significantly higher ACTH response than GWV without PTSD but did not differ from non-exposed subjects. Among GWV, unexplained medical health symptoms (e.g., neurological, musculoskeletal, cardiac, and pulmonary symptoms) and PTSD symptoms were significantly positively associated with the ACTH response to metyrapone.
Gulf War deployment is associated with a substantially lower ACTH response to metyrapone. In contrast, unexplained health symptoms and PTSD in Gulf War veterans are associated with relatively greater hypothalamic-pituitary activity which may reflect increased CRF activity and is evident only in consideration of deployment effects. This pattern of differences suggests either that Gulf War deployment and its associated exposures results in enduring changes in pituitary function or that reduced hypothalamic-pituitary activity protects against the development of PTSD and other deployment-related health problems.
海湾战争部署与一种独特的神经内分泌特征相关，其特点是24小时基础促肾上腺皮质激素（ACTH）水平较低，且皮质醇和ACTH对低剂量地塞米松的抑制作用增强。进行甲吡酮刺激试验以进一步表征海湾战争退伍军人（GWV）的下丘脑 - 垂体活动及其与无法解释的医学症状和创伤后应激障碍（PTSD）的关系。
11名无PTSD的GWV、18名有PTSD的GWV和15名未接触过海湾战争战区的健康受试者（未接触者）接受了甲吡酮刺激试验，该试验抑制皮质醇合成，损害皮质醇介导的负反馈抑制，进而增加ACTH和11 - 脱氧皮质醇（一种皮质醇前体）的水平。这些激素在基线（上午7:00）以及在上午7:05和上午10:05口服750mg甲吡酮后每隔一段时间（从上午8:00至下午4:00）进行测量。
尽管对甲吡酮的皮质醇和11 - 脱氧皮质醇反应相似，但ACTH反应存在组间差异。无PTSD的GWV与未接触者相比，ACTH反应明显减弱；有PTSD的GWV的ACTH反应比无PTSD的GWV明显更高，但与未接触者无差异。在GWV中，无法解释的医学健康症状（如神经、肌肉骨骼、心脏和肺部症状）和PTSD症状与对甲吡酮的ACTH反应显著正相关。
海湾战争部署与对甲吡酮的ACTH反应大幅降低有关。相比之下，海湾战争退伍军人中无法解释的健康症状和PTSD与相对较高的下丘脑 - 垂体活动有关，这可能反映促肾上腺皮质激素释放因子（CRF）活性增加，并且仅在考虑部署影响时才明显。这种差异模式表明，要么海湾战争部署及其相关暴露导致垂体功能的持久变化，要么下丘脑 - 垂体活动降低可预防PTSD和其他与部署相关的健康问题的发生。
