LONGITUDINAL COURSE OF AFFECTIVE ILLNESS--IMPLICATIONS FOR UNDERLYING MECHANISMS

情感疾病的纵向病程——对潜在机制的影响

• 批准号: 3859979
• 负责人: R M POST
• 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/3859979
• 关键词: antidepressants; bipolar depression; bipolar depression manic phase; drug adverse effect; environmental stressor; human subject; hypothyroidism; lithium; longitudinal human study; mental disorder chemotherapy; neuroendocrine system; neurotransmitters; psychological stressor; relapse /recurrence; social integration; stress; tricyclic antidepressant

Methods have been developed to systematically assess and plot the longitudinal course of affective illness in relationship to pharmacological interventions and psychosocial stressors. We have characterized a course of illness systematically in this fashion in more than 196 patients with primary affective disorders. These data re-document the early observations that the course is often not only one of recurrences, but of progressive increases in frequency of cycling and severity of illness. Ultra-rapid and ultradian cycling have also been identified. This cycle acceleration is occurring in the context of a decreasing incidence of psychosocial stressors precipitating affective episodes; i.e., as in sensitization and kindling, they are occurring autonomously. It is against this backdrop that pharmacological intervention must be considered. We have noted that one of the previous traditional interventions for bipolar depression, tricyclic antidepressants, appear to carry a 35% risk of causing definite or likely switches into mania. In those individuals who show this induction, we have observed a pattern of increased rapidity of cycling in the year prior to NIMH admission and longer hospital stays at NIMH, suggesting that TCA-induced switches are a marker if not the cause of a more malignant course of illness. A new phenomenon of lithium discontinuation-induced refractoriness has been described that presents an additional rationale for continuing patients on long-term maintenance treatment. We have begun to assess neurobiological correlates of course of illness using a variety of neurotransmitter and endocrine markers as well as proteins in the CSF. In patients studied after a prolonged period of medication-free evaluation, we have observed that rapid cyclers show significantly higher T4 and free T4 levels compared with non-rapid cyclers. These data are contrary to previous notions in medicated patients, where rapid cycling was often associated with hypothyroidism. In bipolar patients, more lethal suicide attempts appear to occur later in the course of illness in contrast with unipolar patients reported in the literature where these often occur after the first episode.

已经开发了系统评估和绘制 情感性疾病的纵向病程与药物治疗的关系 干预和心理社会压力。 我们描述了一个过程 在超过196名患者中， 原发性情感障碍 这些数据重新记录了早期的观察结果 这一过程往往不仅是一个复发，但渐进的 骑自行车的频率和疾病的严重程度增加。 超快速和 超日循环也已被确认。 这种循环加速是 发生在心理社会事件发生率下降的背景下， 促使情感发作的紧张性刺激;即，如在敏化和 它们是自发发生的。 正是在这种背景下 必须考虑药物干预。 我们注意到 一种以前治疗双相抑郁症的传统方法， 三环类抗抑郁药，似乎有35%的风险， 或者可能会变成躁狂症 在那些表现出这一点的人身上 诱导，我们已经观察到一种模式，增加循环的速度， 在NIMH入院前一年和在NIMH住院更长时间， 这表明，TCA诱导的开关是一个标志，如果不是原因， 更恶性的病程。 锂的新现象 已经描述了中断引起的不应性， 患者继续接受长期维持治疗的其他依据 治疗 我们已经开始评估神经生物学的相关性， 使用多种神经递质和内分泌标记物的疾病 脑脊液中的蛋白质 在经过长时间研究的患者中， 在无药物评估中，我们观察到快速循环者显示 与非快速循环者相比，T4和游离T4水平显著较高。 这些数据与先前对药物治疗患者的概念相反， 快速循环常与甲状腺功能减退有关。 以双极 患者，更致命的自杀企图似乎发生在后期的过程中 与文献报道的单极患者相比， 这些通常发生在第一次发作后。