Department of Psychiatry, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0559, USA.
Psychoneuroendocrinology. 2010 Aug;35(7):1001-7. doi: 10.1016/j.psyneuen.2010.01.001. Epub 2010 Feb 8.
The hypothalamic neuropeptide, orexin-A has a number of regulatory effects in humans and pre-clinical evidence suggests a link to neuroendocrine systems known to be pathophysiologically related to posttraumatic stress disorder (PTSD). However, there are no reports of central nervous system (CNS) or peripheral orexin-A concentrations in patients with PTSD, or any anxiety disorder. Cerebrospinal fluid (CSF) and plasma levels of orexin-A were serially determined in patients with PTSD and healthy comparison subjects to characterize the relationships between orexin-A (in the CNS and peripheral circulation) and central indices of monoaminergic neurotransmission and to determine the degree to which CNS orexin-A concentrations reflect those in the circulating blood. CSF and plasma samples were obtained serially over a 6-h period in 10 male combat veterans with chronic PTSD and 10 healthy male subjects through an indwelling subarachnoid catheter. Orexin-A concentrations were determined in plasma and CSF and CSF levels of the serotonin metabolite, 5-hydroxyindolacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid (HVA), were determined over the sampling period. CSF and plasma orexin-A concentrations were significantly lower in the patients with PTSD as compared with healthy comparison subjects at all time points. In addition, CSF orexin-A concentrations strongly and negatively correlated with PTSD severity as measured by the Clinician-Administered PTSD Scale (CAPS) in patients with PTSD. Peripheral and CNS concentrations of orexin-A were correlated in the healthy comparison subjects and peripheral orexin-A also correlated with CNS serotonergic tone. These findings suggest low central and peripheral orexin-A activity in patients with chronic PTSD are related to symptom severity and raise the possibility that orexin-A is part of the pathophysiological mechanisms of combat-related PTSD.
下丘脑神经肽，食欲素-A 在人类中有许多调节作用，临床前证据表明它与神经内分泌系统有关，而神经内分泌系统与创伤后应激障碍（PTSD）的病理生理学有关。然而，目前尚无 PTSD 患者或任何焦虑障碍患者中枢神经系统（CNS）或外周食欲素-A 浓度的报告。本研究连续测定 PTSD 患者和健康对照者的脑脊液（CSF）和血浆食欲素-A 水平，以描述食欲素-A（在中枢神经系统和外周循环中）与中枢单胺能神经传递的关系，并确定 CNS 食欲素-A 浓度反映循环血液中浓度的程度。通过留置蛛网膜下腔导管，在 10 名患有慢性 PTSD 的男性退伍军人和 10 名健康男性受试者中，在 6 小时的时间内连续获得 CSF 和血浆样本。测定了血浆和 CSF 中的食欲素-A 浓度，以及 CSF 中 5-羟吲哚乙酸（5-HIAA）和多巴胺代谢物高香草酸（HVA）的水平。与健康对照组相比，PTSD 患者在所有时间点的 CSF 和血浆食欲素-A 浓度均显著降低。此外，在 PTSD 患者中，CSF 食欲素-A 浓度与 PTSD 严重程度（由 PTSD 临床医生评定量表（CAPS）评定）呈强烈负相关。在健康对照组中，外周和中枢食欲素-A 浓度呈正相关，外周食欲素-A 也与中枢 5-羟色胺能有关。这些发现表明，慢性 PTSD 患者的中枢和外周食欲素-A 活性较低与症状严重程度有关，并提示食欲素-A 可能是与战斗相关 PTSD 的病理生理机制的一部分。
