From the Department of Psychiatry (K.-C. Yang, Liu, Chou), Taipei Veterans General Hospital; Department of Psychiatry (K.-C. Yang, Liu, Chou), Faculty of Medicine, National Yang Ming Chiao Tung University; Department of Nuclear Medicine (B.-H. Yang), Taipei Veterans General Hospital, Taipei, Taiwan; Department of Biomedical Imaging and Radiological Sciences (B.-H. Yang), National Yang Ming Chiao Tung University; and Center for Quality Management (Chou), Taipei Veterans General Hospital, Taipei, Taiwan.
Psychosom Med. 2022;84(6):685-694. doi: 10.1097/PSY.0000000000001089. Epub 2022 Apr 27.
Cortisol is associated with cognition in both healthy individuals and patients with neuropsychiatric disorders. Regarding the effects of cortisol on the dopamine system and the association between dopamine transporter (DAT) and cognition, DAT might be a central target linking cortisol and cognition. This study explored the role of striatal DAT in the cortisol-cognition relationship.
We recruited 33 patients with carbon monoxide poisoning and 33 age- and sex-matched healthy controls. All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT was used to determine striatal DAT availability. Plasma cortisol, tumor necrosis factor α, and interleukin-10 levels were measured using enzyme-linked immunosorbent assays.
Compared with healthy controls, patients with carbon monoxide poisoning had lower cognitive performance, bilateral striatal DAT availability, and plasma tumor necrosis factor-α levels and higher cortisol and interleukin-10 levels. In all participants, plasma cortisol level and bilateral striatal DAT availability were negatively and positively related to cognition, respectively, including memory and executive function with β from -0.361 (95% confidence interval [CI] = -0.633 to -0.090) to 0.588 (95% CI = 0.319 to 0.858). Moreover, bilateral striatal DAT mediated the cortisol-cognition relationship with indirect effects from -0.067 (95% CI = -0.179 to -0.001) to -0.135 (95% CI = -0.295 to -0.024). The cytokine levels did not influence the mediation effects.
This is the first study to demonstrate that striatal DAT mediates the cortisol-cognition relationship. Future studies are needed to comprehensively evaluate the role of the dopamine system in cortisol-cognition associations and treatment implications.
皮质醇与健康个体和神经精神疾病患者的认知功能有关。关于皮质醇对多巴胺系统的影响以及多巴胺转运体（DAT）与认知之间的关系，DAT 可能是连接皮质醇和认知的核心靶点。本研究探讨了纹状体 DAT 在皮质醇-认知关系中的作用。
我们招募了 33 名一氧化碳中毒患者和 33 名年龄和性别匹配的健康对照者。所有参与者均接受注意力、记忆和执行功能的认知评估。使用 99mTc-TRODAT 单光子发射计算机断层扫描测定纹状体 DAT 可利用度。采用酶联免疫吸附试验测定血浆皮质醇、肿瘤坏死因子-α和白细胞介素-10 水平。
与健康对照组相比，一氧化碳中毒患者的认知表现、双侧纹状体 DAT 可利用度以及血浆肿瘤坏死因子-α水平较低，而皮质醇和白细胞介素-10 水平较高。在所有参与者中，血浆皮质醇水平与双侧纹状体 DAT 可利用度分别与认知呈负相关和正相关，包括记忆和执行功能，β值分别为-0.361（95%置信区间[CI]：-0.633 至-0.090）至 0.588（95%CI：0.319 至 0.858）。此外，双侧纹状体 DAT 介导了皮质醇-认知关系，间接效应为-0.067（95%CI：-0.179 至-0.001）至-0.135（95%CI：-0.295 至-0.024）。细胞因子水平不影响中介效应。
这是第一项表明纹状体 DAT 介导皮质醇-认知关系的研究。需要进一步的研究来全面评估多巴胺系统在皮质醇-认知关联中的作用和治疗意义。
