Rights statement: The final, definitive version of this article has been published in the Journal, Journal of Psychopharmacology, 29 (2), 2015, © SAGE Publications Ltd, 2015 by SAGE Publications Ltd at the Journal of Psychopharmacology page: http://jop.sagepub.com/ on SAGE Journals Online: http://online.sagepub.com/
Accepted author manuscript, 232 KB, PDF document
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Functional brain connectivity phenotypes for schizophrenia drug discovery
AU - Dawson, Neil
AU - Morris, Brian J.
AU - Pratt, Judith
N1 - The final, definitive version of this article has been published in the Journal, Journal of Psychopharmacology, Vol. 29(2): 169-177, 2015, © SAGE Publications Ltd, 2015 by SAGE Publications Ltd at the Journal of Psychopharmacology page: http://jop.sagepub.com/ on SAGE Journals Online: http://online.sagepub.com/
PY - 2015/2
Y1 - 2015/2
N2 - While our knowledge of the pathophysiology of schizophrenia has increased dramatically, this has not translated into the development of new and improved drugs to treat this disorder. Human brain imaging and electrophysiological studies have provided dramatic new insight into the mechanisms of brain dysfunction in the disease, with a swathe of recent studies highlighting the differences in functional brain network and neural system connectivity present in the disorder. Only recently has the value of applying these approaches in preclinical rodent models relevant to the disorder started to be recognised. Here we highlight recent findings of altered functional brain connectivity in preclinical rodent models and consider their relevance to those alterations seen in the brains of schizophrenia patients. Furthermore, we highlight the potential translational value of using the paradigm of functional brain connectivity phenotypes in the context of preclinical schizophrenia drug discovery, as a means both to understand the mechanisms of brain dysfunction in the disorder and to reduce the current high attrition rate in schizophrenia drug discovery.
AB - While our knowledge of the pathophysiology of schizophrenia has increased dramatically, this has not translated into the development of new and improved drugs to treat this disorder. Human brain imaging and electrophysiological studies have provided dramatic new insight into the mechanisms of brain dysfunction in the disease, with a swathe of recent studies highlighting the differences in functional brain network and neural system connectivity present in the disorder. Only recently has the value of applying these approaches in preclinical rodent models relevant to the disorder started to be recognised. Here we highlight recent findings of altered functional brain connectivity in preclinical rodent models and consider their relevance to those alterations seen in the brains of schizophrenia patients. Furthermore, we highlight the potential translational value of using the paradigm of functional brain connectivity phenotypes in the context of preclinical schizophrenia drug discovery, as a means both to understand the mechanisms of brain dysfunction in the disorder and to reduce the current high attrition rate in schizophrenia drug discovery.
KW - EEG
KW - fMRI
KW - default node network
KW - graph theory
KW - genetic risk factors
KW - NMDA receptor
KW - hippocampal-prefrontal connectivity
KW - thalamic connectivity
U2 - 10.1177/0269881114563635
DO - 10.1177/0269881114563635
M3 - Journal article
VL - 29
SP - 169
EP - 177
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
SN - 0269-8811
IS - 2
ER -