Document Detail


Schizophrenia, myelination, and delayed corollary discharges: a hypothesis.
MedLine Citation:
PMID:  20855415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Thomas J Whitford; Judith M Ford; Daniel H Mathalon; Marek Kubicki; Martha E Shenton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-09-20
Journal Detail:
Title:  Schizophrenia bulletin     Volume:  38     ISSN:  1745-1701     ISO Abbreviation:  Schizophr Bull     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-08-30     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  0236760     Medline TA:  Schizophr Bull     Country:  United States    
Other Details:
Languages:  eng     Pagination:  486-94     Citation Subset:  IM    
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
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MeSH Terms
Descriptor/Qualifier:
Dopamine / physiology*
Frontal Lobe / metabolism,  pathology,  physiopathology*
Humans
Myelin Sheath / metabolism,  pathology*
Psychological Theory
Schizophrenia / etiology*,  metabolism,  physiopathology
Grant Support
ID/Acronym/Agency:
K02 MH067967/MH/NIMH NIH HHS; K05 MH 070047/MH/NIMH NIH HHS; P50 MH 080272/MH/NIMH NIH HHS; R01 MH 50747/MH/NIMH NIH HHS; R01 MH058262/MH/NIMH NIH HHS; R01 MH076989/MH/NIMH NIH HHS; R03 MH068464-0/MH/NIMH NIH HHS
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