title: 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.
authors.affiliation: Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, 1249 Boylston Street, Boston, MA 02215, USA. whitford@bwh.harvard.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Whitford
authors.forename: Judith M
authors.initials: JM
authors.lastname: Ford
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Mathalon
authors.forename: Marek
authors.initials: M
authors.lastname: Kubicki
authors.forename: Martha E
authors.initials: ME
authors.lastname: Shenton
mesh_terms: D004298:Dopamine / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D011582:Psychological Theory; D012559:Schizophrenia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004298:Dopamine