NEUROBIOLOGY OF SEASONAL AFFECTIVE DISORDER AND LIGHT THERAPY

季节性情感障碍的神经生物学和光疗法

• 批准号: 3781365
• 负责人: N E ROSENTHAL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3781365
• 关键词: adrenocorticotropic hormone; antidepressants; bioperiodicity; body temperature; cortisol; hormone regulation /control mechanism; human subject; human therapy evaluation; hypothalamic pituitary axis; lighting; neurobiology; phototherapy; pituitary adrenal axis; platelets; prolactin; seasonal affective disorder; serotonin; sympathetic nervous system

Although repeated studies have established that bright light is an effective treatment for SAD, the mechanisms of its actions remains unknown, as do the fundamental biological abnormalities responsible for the syndrome. There is ample reason to believe that brain serotonergic systems may be involved in these processes. Last year we reported that SAD patients respond abnormally, with exaggerated activation and euphoria, to infusions of the serotonin agonist, m-CPP. We have followed up this previous report on the hormonal and temperature responses of the same patients to this challenge study. This year we extended our research to test the hypothesis that serotonergic transmission is an important regulator of mood in SAD patients by attempting to reverse the antidepressant effects of light therapy and exacerbate depression i these same individuals by reducing brain serotonin levels. We attempted to accomplish this by manipulating dietary macronutrients to induce biochemical changes. We also studied peripheral markers of serotonin function by measuring parameters of platelet binding. Platelets respond to serotonin and antidepressant medications in plasma in a similar fashion as brain cells. A third study followed up on our previous study of the role of the eye and its connections to the brain in the pathogenesis of SAD, by comparing patients and controls in winter and summer conditions. Finally, a group of SAD patients an controls were studied in winter and summer in order to understand sympathetic nervous system response and the hypothalamo-pituitary-adrenal (HPA) axis. SAD patients and controls were given m-CPP or placebo infusions on separate days in untreated and light therapy treated conditions in a randomized block design. For 90 minutes following infusion blood was drawn for prolactin, cortisol, and ACTH. Core and peripheral body temperature were also taken. Plasma prolactin and cortisol levels showed a trend toward the previous findings (hypersecretion in SAD patients), but did not replicate those findings. no difference between patient and control group was found for core body temperature. Light treatment lowered overnight temperature in both groups. Patients had higher peripheral body temperature which rose towards normal levels during light therapy. In the platelet study no differences were found between SAD patients and controls in any of the measures and between light therapy conditions in SAD patient A group of SAD patients and controls in winter and summer were administered a standard ocular paradigm and an EOG was taken. A significant season y group difference was found (F=4.84, G-G p<.05) in which controls had a significantly higher EOG ratio in winter than patients or than in both groups in summer. The study of the sympathetic nervous system and HPA axis is ongoing, and as yet there are no findings.

尽管反复的研究已经确定明亮的光线是一种 SAD的有效治疗，其作用机制仍然未知， 以及造成这些疾病的基本生物学异常 综合征 有充分的理由相信，大脑中的肾上腺素能系统 可能参与了这些过程。 去年我们报道说， 患者对药物的反应异常，具有过度的激活和欣快， 注射5-羟色胺激动剂m-CPP 我们已经跟进此事 以前的报告，对激素和温度的反应， 患者参加这项挑战研究。 今年我们将研究范围扩大到 测试这一假设，即多巴胺能传输是一个重要的 情绪调节器在SAD患者试图扭转 光疗法的抗抑郁作用，并加剧抑郁症， 通过降低大脑中的血清素水平。 我们试图 通过操纵膳食常量营养素来诱导 生化变化 我们还研究了血清素的外周标记物 通过测量血小板结合的参数来发挥作用。 坦率地回答 血清素和抗抑郁药物在血浆中以类似的方式 脑细胞 第三项研究是对我们之前关于 在SAD的发病机制中，眼睛及其与大脑的联系， 在冬季比较患者和对照组 夏天的条件。 最后，一组SAD患者和一组对照组被 在冬季和夏季进行研究，以了解交感神经 系统反应和下丘脑-垂体-肾上腺（HPA）轴。 SAD患者和对照组分别接受m-CPP或安慰剂输注， 在随机化的未治疗和光疗法治疗的条件下， 区组设计 在输注后90分钟内，抽取血液， 催乳素皮质醇和促肾上腺皮质激素 核心和外周体温分别为 也采取。 血浆催乳素和皮质醇水平显示出 既往发现（SAD患者分泌过多），但未重复 这些发现。 患者与对照组之间无差异 核心体温 光处理降低过夜温度 在两组中。 患者外周体温升高， 恢复到正常水平 在血小板研究中，SAD患者和 SAD中任何测量中以及光治疗条件之间的对照 患者 对SAD患者和对照组在冬夏两季进行了研究， 采用标准眼模式并进行EOG。 一个重要的季节Y 组间差异（F=4.84，G-G p<0.05），其中对照组有 冬季EOG比值显著高于患者或两者 夏天的团体 交感神经系统和HPA轴的研究正在进行中， 但没有任何发现。