University of Michigan Department of Psychiatry, Trauma, Stress and Anxiety Research Group, Molecular and Behavioral Neuroscience Institute, United States.
Psychoneuroendocrinology. 2010 Apr;35(3):451-9. doi: 10.1016/j.psyneuen.2009.08.007. Epub 2009 Sep 16.
The hypothalamic-pituitary adrenal (HPA) axis is critical for biobehavioral adaptation to challenge and appears dysregulated in a range of psychiatric disorders. Its precise role in psychopathology remains unclear and discrepant and difficult to explain findings abound in the clinical literature. Basic research suggests this system is sensitive to psychosocial cues, but psychosocial milieu factors are rarely controlled or examined in psychiatric studies using biological probes of the HPA axis. To test the hypothesis that psychological factors might complicate HPA study results even in direct, pharmacological challenge paradigms, endocrine responses to corticotropin-releasing hormone (CRH) were examined under two different cognitive preparation conditions.
Healthy subjects (n=32) received standard instructions or a cognitive intervention (CI) prior to injection with CRH and placebo, given on separate days in random order. The CI combined access to control over drug exposure with novelty reduction and coping enhancement. Blood samples were obtained via intravenous catheter before and after CRH.
Cognitive intervention reduced corticotropin (ACTH) levels, but only when CRH was given first (intervention by order interaction). It did not reduce cortisol response. The CI and visit (1st or 2nd) both impacted cortisol levels on placebo day.
Modifiable psychological factors may amplify or inhibit HPA axis activity in pharmacological activation paradigms, including CRH stimulation tests. The factors manipulated by the CI (novelty/familiarity, control and coping) may have particular salience to the HPA axis. Differential sensitivity to such factors could impact results in studies applying biological HPA probes to psychiatric populations.
下丘脑-垂体-肾上腺（HPA）轴对于生物行为适应挑战至关重要，并且在多种精神疾病中出现失调。其在精神病理学中的确切作用仍不清楚，临床文献中存在大量不一致且难以解释的发现。基础研究表明，该系统对心理社会线索敏感，但在使用 HPA 轴生物学探针的精神科研究中，很少控制或检查心理社会环境因素。为了检验心理因素可能使 HPA 研究结果复杂化的假设，即使在直接的药理学挑战范式中也是如此，在两种不同的认知准备条件下检查了促肾上腺皮质激素释放激素（CRH）的内分泌反应。
健康受试者（n=32）在接受 CRH 和安慰剂注射前分别接受标准指令或认知干预（CI），并以随机顺序在不同天进行。CI 结合了对药物暴露的控制、新奇感降低和应对能力增强。在 CRH 给药前后通过静脉内导管采集血样。
认知干预降低了促皮质激素（ACTH）水平，但仅在 CRH 首先给药时（干预与顺序的交互作用）。它并没有降低皮质醇反应。CI 和访问（第 1 天或第 2 天）都会影响安慰剂日的皮质醇水平。
可调节的心理因素可能在药理学激活范式中放大或抑制 HPA 轴活动，包括 CRH 刺激测试。CI 操纵的因素（新奇/熟悉度、控制和应对）可能对 HPA 轴具有特殊意义。对这些因素的不同敏感性可能会影响将生物 HPA 探针应用于精神科人群的研究结果。
