Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA 02215, USA.
Schizophr Bull. 2012 May;38(3):486-94. doi: 10.1093/schbul/sbq105. Epub 2010 Sep 20.
Any etiological theory of schizophrenia must account for at least 3 distinctive features of the disorder, namely its excessive dopamine neurotransmission, its frequent periadolescent onset, and its bizarre, pathognomonic symptoms. In this article, we theorize that each of these features could arise from a single underlying cause--namely abnormal myelination of late-developing frontal white matter fasciculi. Specifically, we suggest that abnormalities in frontal myelination result in conduction delays in the efference copies initiated by willed actions. These conduction delays cause the resulting corollary discharges to be generated too late to suppress the sensory consequences of the willed actions. The resulting ambiguity as to the origins of these actions represents a phenomenologically and neurophysiologically significant prediction error. On a phenomenological level, the perception of salience in a self-generated action leads to confusion as to its origins and, consequently, passivity experiences and auditory hallucinations. On a neurophysiological level, this prediction error leads to the increased activity of dopaminergic neurons in the midbrain. This dopaminergic activity causes previously insignificant events to be perceived as salient, which exacerbates the budding hallucinations and passivity experiences and triggers additional first-rank symptoms such as delusions of reference. The article concludes with a discussion of the implications of the theory and some testable predictions which may form a worthwhile basis for future research.
精神分裂症的任何病因理论都必须至少解释该疾病的 3 个独特特征，即其多巴胺神经递质的过度传递、其常见的青春期发病和其奇异的、特征性的症状。在本文中，我们推断这些特征中的每一个都可能源于一个单一的根本原因——即发育后期额叶白质束的异常髓鞘形成。具体来说，我们认为额叶髓鞘异常导致意志行为引发的传出冲动的复制出现传导延迟。这些传导延迟导致相应的传出放电产生得太晚，无法抑制意志行为的感觉后果。由此导致的这些行为起源的模糊性代表了一种在现象学和神经生理学上具有重要意义的预测误差。在现象学层面上，自我产生的行为的显着性感知导致对其起源的混淆，进而导致被动体验和听觉幻觉。在神经生理学层面上，这种预测误差导致中脑多巴胺能神经元活动增加。这种多巴胺能活动导致以前不重要的事件被感知为显着，从而加剧了萌芽的幻觉和被动体验，并引发了其他一级症状，如牵连观念。本文最后讨论了该理论的意义和一些可测试的预测，这些预测可能为未来的研究提供有价值的基础。
