Theories of schizophrenia: a genetic-inflammatory-vascular synthesis.
Theories of schizophrenia: a genetic-inflammatory-vascular synthesis.
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DOI：
10.1186/1471-2350-6-7
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发表时间：
2005-02-11
影响因子：
--
通讯作者：
Gottesman II
中科院分区：
文献类型：
--
作者：
Hanson DR;Gottesman II
精神分裂症是一种相对常见的精神综合征，几乎影响所有的大脑功能，但100多年来一直无法解释。无论是通过发育和/或退化过程，神经元及其突触连接的异常一直是最近关注的焦点。然而，我们无法理解精神分裂症的病理生理学，迫使我们挑战我们的理论模型和信念。寻找一个更令人满意的模型来解释精神分裂症的各个方面，揭示了指向遗传介导的CNS微血管炎性疾病的线索。精神分裂症理论中的一个血管成分假定，导致疾病的生理异常涉及对正常大脑功能所需的能量和氧气输送的精确调节的破坏。该理论进一步提出，CNS代谢异常的出现是因为遗传调节的炎症反应在对环境因子（包括感染、缺氧和物理创伤）的反应中损害了大脑的微血管系统。损伤可能随着反复暴露于触发剂而累积，导致恶化和恶化，或随着它们的去除而愈合。有明确的例子表明，炎症调节因子的遗传多态性会导致炎症反应过度。也有充分的证据表明，大脑的炎性血管疾病可以导致精神病，经常是盛衰，并表现出波动的过程，如精神分裂症。使用新旧技术在精神分裂症患者中反复观察到中枢神经系统血流紊乱。为了解释精神分裂症中无数的行为和其他奇怪的发现，如轻微的身体异常，或报告的类风湿性关节炎和高度可见的甲襞毛细血管的发病率下降，我们必须唤起一个系统性的过程，如血管和免疫/炎症系统。精神分裂症的血管炎症理论将环境和遗传因素结合在一起，可以解释观察到的症状和结果的多样性。如果这些想法得到证实，它们将通过避免炎症诱导物或通过炎症调节剂的方式为治疗或预防带来新的方向，从而防止过度炎症和随后在遗传易感人群中引发精神病发作。
Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons.