Stephan, K. E.;
Friston, K. J.;
Frith, C. D.;
(2009)
Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring.
Schizophrenia Bulletin
, 35
(3)
pp. 509-527.
10.1093/schbul/sbn176.
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Abstract
Over the last 2 decades, a large number of neurophysiological and neuroimaging studies of patients with schizophrenia have furnished in vivo evidence for dysconnectivity, ie, abnormal functional integration of brain processes. While the evidence for dysconnectivity in schizophrenia is strong, its etiology, pathophysiological mechanisms, and significance for clinical symptoms are unclear. First, dysconnectivity could result from aberrant wiring of connections during development, from aberrant synaptic plasticity, or from both. Second, it is not clear how schizophrenic symptoms can be understood mechanistically as a consequence of dysconnectivity. Third, if dysconnectivity is the primary pathophysiology, and not just an epiphenomenon, then it should provide a mechanistic explanation for known empirical facts about schizophrenia. This article addresses these 3 issues in the framework of the dysconnection hypothesis. This theory postulates that the core pathology in schizophrenia resides in aberrant N-methyl-D-aspartate receptor (NMDAR)–mediated synaptic plasticity due to abnormal regulation of NMDARs by neuromodulatory transmitters like dopamine, serotonin, or acetylcholine. We argue that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups. Finally, we test the explanatory power of our theory against a list of empirical facts about schizophrenia.
| Type: | Article |
|---|---|
| Title: | Dysconnection in schizophrenia: from abnormal synaptic plasticity to failures of self-monitoring |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/schbul/sbn176 |
| Publisher version: | http://dx.doi.org/10.1093/schbul/sbn176 |
| Language: | English |
| Additional information: | Published by Oxford University Press 2009. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Dysconnectivity, corollary discharge, psychosis, hallucinations, delusions, NMDA, dopamine, acetylcholine, serotonin, effective connectivity, dynamic causal modeling, DCM, predictive coding |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/20150 |
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