Schizophrenia, Myelination, and Delayed Corollary Discharges: A Hypothesis

Abstract

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.

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

“…Thus our findings lend support to the hypothesis of delayed corollary discharges underlying psychosis. 8,9 We found a positive correlation between positive symptoms and FA in the right AF and a negative correlation between positive symptoms and FA in the right SLF (Fig. 2).…”

“…9 We chose the ROI approach to take advantage of its higher regional sensitivity as compared with a whole brain voxelbased method. As opposed to TBSS, the ROI method estimates the integrity of entire ROIs, rather than the central integrity of the tract only.…”

“…6,7 Two independent research groups recently proposed more comprehensive models of schizophrenia. 8,9 The models imply that disturbances in the reward system 10,11 may stem from J Psychiatry Neurosci 2016;41 (2) irregularities in myelination and subsequent delayed "corollary discharges." 8,9 Corollary discharges comprise early efferent information, which is initiated by willed actions.…”

“…8,9 The models imply that disturbances in the reward system 10,11 may stem from J Psychiatry Neurosci 2016;41 (2) irregularities in myelination and subsequent delayed "corollary discharges." 8,9 Corollary discharges comprise early efferent information, which is initiated by willed actions. Alterations in white matter tracts will increase or decrease the communication between spatially separate brain regions.…”

Failing to self-ascribe thought and motion: Towards a three-factor account of passivity symptoms in schizophrenia

“…6 The idea of corollary discharge being central to explanations of passivity symptoms is still a popular approach being pursued in psychopathology research, e.g. Whitford et al, 2012 andThakkar et al, 2013. 7 Here is a version of the corollary discharge/efferent copy theory for passivity symptoms.…”