LONGITUDINAL COURSE OF AFFECTIVE ILLNESS--IMPLICATIONS FOR UNDERLYING MECHANISMS

已经开发出方法来系统地评估和绘制 情感性疾病的纵向病程与药理学的关系 干预和心理社会压力源。我们已经确定了一门课程的特点 在196多名患有这种疾病的患者中以这种方式系统地 原发情感障碍。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反复，而且是一个渐进的过程 骑自行车的频率和疾病严重程度的增加。超高速和 超级趣味的自行车运动也被发现了。这种周期加速是 发生在社会心理疾病发病率下降的背景下 导致情感发作的应激源；即，在敏化和 在点燃过程中，它们是自动发生的。正是在这样的背景下 必须考虑药物干预。我们注意到， 这是之前治疗双相情感障碍的传统干预措施之一， 三环类抗抑郁药，似乎有35%的风险导致明确 或者很可能会变成狂热。在那些表现出这一点的人身上 诱导后，我们观察到了一种骑行速度增加的模式 NIMH入院前一年和在NIMH住院时间较长的前一年， 这表明TCA诱导的开关即使不是 更恶性的病程。锂的一种新现象 已经描述了由停药引起的不稳定，呈现出一种 继续接受长期维持治疗的患者的其他理由 治疗。当然，我们已经开始评估神经生物学的相关性。 疾病也使用各种神经递质和内分泌标记物 作为脑脊液中的蛋白质。在长期服药后研究的患者 在不用药物的评估中，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水平显著升高。 这些数据与以前在药物治疗患者中的概念相反， 快速循环常与甲状腺功能减退有关。处于两极状态 患者，更致命的自杀企图似乎发生在病程较晚的时候。 与文献中报道的单相患者相比 这些通常发生在第一集之后。

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.