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.

已经开发出方法来系统地评估和绘制 与药物相关的情感疾病的纵向病程 干预措施和社会心理压力源。 我们已经描述了一个课程 以这种方式系统地对超过 196 名患有此病的患者进行了疾病诊断 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种复发，而且是一种渐进的过程 骑自行车的频率和疾病的严重程度增加。 超快速和 超电循环也已被确定。 该循环加速度为 发生在心理社会发生率下降的背景下 诱发情感发作的压力源；即，如敏化和 点燃，它们是自主发生的。 正是在这样的背景下 必须考虑药物干预。 我们注意到 以前治疗双相抑郁症的传统干预措施之一， 三环类抗抑郁药，似乎有 35% 的风险引起明确的抑郁症 或可能转变为狂热。 在那些表现出这一点的人中 诱导后，我们观察到循环速度增加的模式 入院前一年以及在 NIMH 住院时间较长， 表明 TCA 诱导的转换即使不是原因，也是一个标志 病程更加恶性。 锂的新现象 据描述，停药引起的不应性表现出 继续接受长期维持治疗的患者的额外理由 治疗。 当然，我们已经开始评估神经生物学相关性 还使用各种神经递质和内分泌标记物来治疗疾病 作为脑脊液中的蛋白质。 在经过长时间研究的患者中 无药物评估，我们观察到快速循环仪显示 与非快速循环仪相比，T4 和游离 T4 水平显着升高。 这些数据与之前对接受药物治疗的患者的看法相反，其中 快速循环通常与甲状腺功能减退症有关。 双极性 患者，更多致命的自杀企图似乎发生在病程后期 与文献报道的单相情感障碍患者相比，疾病发生率 这些通常发生在第一集之后。