SEROTONERGIC ABNORMALITIES IN SEASONAL AFFECTIVE DISORDER AND LIGHT THERAPY

季节性情感障碍和光疗中的血清素异常

• 批准号: 6111189
• 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/6111189
• 关键词: cell line; clinical research; genetic polymorphism; human subject; human therapy evaluation; phototherapy; piperazines; positron emission tomography; psychopharmacology; seasonal affective disorder; serotonin; serotonin inhibitor; serotonin transporter; sleep disorders; tyrosine 3 monooxygenase; visible light

Our prior research suggests that serotonergic mechanisms are involved in the pathophysiology of seasonal affective disorder (SAD) and the therapeutic action of light therapy. Given abnormal activation-euphoric responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP) in patients with SAD, we tested the hypothesis that SAD patients would also exhibit abnormal cerebral metabolic responses to this drug, as measured by positron emission tomography (PET) scanning. Results confirmed previous findings of activation-euphoria in patients compared to controls following m-CPP administration. We found no global differences in cerebral metabolism in patients as compared to controls either at baseline or following the drug challenge. The possibility of regional cerebral metabolic differences in patients await future data analysis. In a second PET scan study we tested the hypotheses that (1) one hour of light therapy would tend to normalize the level of blood flow in limbic and paralimbic regions of the brain and exert no effect on controls and (2) the antidepressant response to light therapy following one hour of exposure will correlate with the antidepressant response after one and two weeks of light therapy. Results await future data analysis. To investigate whether the antidepressant effects of light therapy might occur through either serotonergic or catecholaminergic mechanisms, patients remitted on light therapy underwent independent depletions of serotonin and catecholamines. Serotonin and catecholamines were depleted with a tryptophan-free amino acid beverage (plus amino acid capsules) and the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine. Both depletion procedures, compared to sham depletion, equally reversed the antidepressant effects of light therapy. In ongoing studies of lymphoblastoid cell lines, we have attempted to find abnormal polymorphisms in genes related to serotonergic functioning in SAD patients. We have found that the short allele of the 5-HT transporter-linked polymorphism (5-HTTLPR) is associated with SAD, as well as with greater levels of seasonality (seasonally-related behavioral changes such as mood, energy, appetite) in patients with SAD.

我们先前的研究表明，多巴胺能机制参与了 季节性情感障碍（SAD）的病理生理学和 光疗法的治疗作用。 鉴于异常激活-欣快 对5-羟色胺激动剂间氯苯基哌嗪（m-CPP）的反应， 对于SAD患者，我们测试了SAD患者也会 表现出对该药物的异常脑代谢反应，如通过 正电子发射断层扫描（PET）。 先前确认的结果 与对照组相比， m-CPP给药。 我们没有发现大脑的整体差异， 与对照组相比，基线或 在药物挑战之后。 可能是局部脑 患者的代谢差异有待于未来的数据分析。 在第二 PET扫描研究，我们测试的假设，（1）一个小时的光治疗 会使大脑边缘系统和脑边缘系统的血流水平正常化 大脑的区域，并不对控制产生影响，以及（2） 暴露1小时后对光疗法的抗抑郁反应 将与抗抑郁药的反应有关， 光疗法 结果有待未来的数据分析。 为了研究光疗法的抗抑郁作用是否可能 通过肾上腺素能或儿茶酚胺能机制发生， 光疗法缓解的患者接受了独立的 血清素和儿茶酚胺。 血清素和儿茶酚胺被耗尽 不含色氨酸的氨基酸饮料（加上氨基酸胶囊）， 酪氨酸羟化酶抑制剂α-甲基-对-酪氨酸。 两 与假耗竭相比，耗竭程序同样逆转了 光疗法的抗抑郁作用。 在正在进行的关于 淋巴母细胞样细胞系，我们试图找到异常 SAD患者肾上腺素能功能相关基因的多态性 患者 我们发现5-HT的短等位基因 转运蛋白连锁多态性（5-HTTLPR）也与SAD相关 随着季节性（季节性相关的行为）水平的提高， 情绪、精力、食欲等变化）。