Bipolar Collaborative Network, 5415 W Cedar Lane, Suite 201-B, Bethesda, MD 20814, United States.
J Psychiatr Res. 2012 May;46(5):561-73. doi: 10.1016/j.jpsychires.2012.02.004. Epub 2012 Mar 23.
Some clinical aspects of affective illness progression, such as episode-, stress-, and substance-induced sensitization, have been well documented in the literature, but others have received less attention. These include cognitive deficits, treatment-refractoriness, and neurobiological correlates of illness progression, which are the primary focus of this paper. We review the evidence that cognitive dysfunction, treatment resistance, medical comorbidities, and neurobiological abnormalities increase as a function of the number of prior episodes or duration of illness in the recurrent unipolar and bipolar disorders. Substantial evidence supports the view that cognitive dysfunction and vulnerability to a diagnosis of dementia in old age increases as a function of number of prior mood episodes as does non-response to many therapeutic interventions as well as naturalistic treatment. Neurobiological abnormalities that correlate with the number of mood episodes or duration of illness include: anatomical, functional, and biochemical deficits in the prefrontal cortex and hippocampus, as well as amygdala hyperactivity and cortisol hyper-secretion. Some neurotrophic factors and inflammatory markers may also change with greater illness burden. Causality cannot be inferred from these correlative relationships. Nonetheless, given the potentially grave consequences of episode recurrence and progression for morbidity and treatment non-responsiveness, it is clinically wise to assume episodes are causing some of the progressive cognitive and neurobiological abnormalities. As such, earlier and more sustained long-term prophylaxis to attempt to reduce these adverse outcomes is indicated.
一些情感障碍进展的临床方面，如发作、应激和物质诱导的敏感化，在文献中已有很好的记录，但其他方面则较少受到关注。这些方面包括认知缺陷、治疗抵抗和疾病进展的神经生物学相关性，这是本文的主要焦点。我们回顾了证据，表明认知功能障碍、治疗抵抗、合并医学疾病以及神经生物学异常随着复发性单相和双相情感障碍的发作次数或疾病持续时间的增加而增加。大量证据支持这样一种观点，即认知功能障碍和老年痴呆症的易感性随着情绪发作次数的增加而增加，就像对许多治疗干预措施以及自然治疗的反应不佳一样。与情绪发作次数或疾病持续时间相关的神经生物学异常包括：前额叶皮层和海马体的解剖、功能和生化缺陷，以及杏仁核过度活跃和皮质醇过度分泌。一些神经营养因子和炎症标志物也可能随着疾病负担的增加而发生变化。不能从这些相关性中推断出因果关系。尽管如此，鉴于发作复发和进展对发病率和治疗反应性的潜在严重后果，临床上有理由假设发作导致了一些进行性认知和神经生物学异常。因此，需要更早和更持续的长期预防治疗，以试图减少这些不良后果。
