双相情感障碍 (BD) 是一种主要的精神疾病，影响高达 5% 的人口。双相情感障碍可以随着时间的推移发展为慢性“神经进行性”病程，并伴有认知和功能障碍。目前，没有经过验证的预测因素表明哪些患者将出现神经进展病程，也没有具体的治疗方法。这篇综述提供了支持双相神经进展机制的新假设的数据。 52% 的 BD 患者存在胰岛素抵抗 (IR)，并且与慢性病程、治疗无反应、不良脑部变化和认知障碍有关。此外，IR 发作后双相情感障碍发病率增加 12 倍，表明 IR 可能会改变疾病进展。我回顾了 IR 是神经进展中可测试和可治疗的调节因素的证据，并且逆转 IR 可能是某些患者获得缓解的有效（也许是唯一）方法。我将其与消化性溃疡病中的幽门螺杆菌进行了类比（一种新机制，将两种以前不相关的现象结合在一起，从而揭示了一种新的治疗方法）。这种双相情感障碍进展模型结合了 IR 和 BD 之间共有的失调机制，可以进行早期筛查、病例发现和神经进展监测，并有可能进行干预以预防晚期双相情感障碍。关键信息 双相情感障碍的神经进展是指更严重的疾病形式和较差的结果。目前，还没有经过验证的神经进展预测因子，可以帮助指导治疗和改善预后。 超过一半的双相情感障碍患者存在胰岛素抵抗，并与慢性病程、对情绪稳定治疗缺乏反应、认知障碍和功能结果不佳有关。胰岛素抵抗可能会改变双相情感障碍的病程并促进神经进展。胰岛素抵抗可能是双相情感障碍神经进展的可测试且潜在可改变的危险因素。
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Insulin resistance takes center stage: a new paradigm in the progression of bipolar disorder.
Bipolar Disorder (BD) is a major psychiatric illness affecting up to 5% of the population. BD can progress over time to a chronic "neuroprogressive" course with cognitive and functional impairment. Currently, there are no validated predictors indicating which patients will develop a neuroprogressive course and there are no specific treatments. This review presents data supporting a novel hypothesis on the mechanisms underlying bipolar neuroprogression. Insulin resistance (IR) is present in 52% of BD patients and is associated with chronic course, treatment nonresponse, adverse brain changes and cognitive impairment. Further, bipolar morbidity increases 12-fold following the onset of IR indicating that IR may modify disease progression. I review evidence that IR is a testable and treatable modifying factor in neuroprogression and that reversing IR may be an efficient (and perhaps the only) means of obtaining remission in some patients. I draw a parallel with Helicobacter pylori in peptic ulcer disease (a novel mechanism that brought together two previously unrelated phenomena that uncovered a new treatment approach). This model of bipolar progression combines shared dysregulated mechanisms between IR and BD, allowing for early screening, case finding, and monitoring for neuroprogression, with the potential for intervention that could prevent advanced bipolar illness. KEY MESSAGES Neuroprogression in bipolar disorder is defined by a more severe form of illness and poor outcome. Currently, there are no validated predictors of neuroprogression, which could help inform treatment and improve prognosis. Insulin resistance is present in more than half of all bipolar patients and is associated with a chronic course of illness, lack of response to mood stabilizing treatment, cognitive impairment and poor functional outcomes. Insulin resistance may modify the course of bipolar disorder and promote neuroprogression. Insulin resistance may be a testable and potentially modifiable risk factor for neuroprogression in bipolar disorder.
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