Neurocognitive endophenotypes of obsessive-compulsive disorder
Neurocognitive endophenotypes of obsessive-compulsive disorder
Endophenotypes (intermediate phenotypes) are objective, heritable, quantitative traits hypothesized to represent genetic risk for polygenic disorders at more biologically tractable levels than distal behavioural and clinical phenotypes. It is theorized that endophenotype models of disease will help to clarify both diagnostic classification and aetiological understanding of complex brain disorders such as obsessive-compulsive disorder (OCD). To investigate endophenotypes in OCD, we measured brain structure using magnetic resonance imaging (MRI), and behavioural performance on a response inhibition task (Stop-Signal) in 31 OCD patients, 31 of their unaffected first-degree relatives, and 31 unrelated matched controls. Both patients and relatives had delayed response inhibition on the Stop-Signal task compared with healthy controls. We used a multivoxel analysis method (partial least squares) to identify large-scale brain systems in which anatomical variation was associated with variation in performance on the response inhibition task. Behavioural impairment on the Stop-Signal task, occurring predominantly in patients and relatives, was significantly associated with reduced grey matter in orbitofrontal and right inferior frontal regions and increased grey matter in cingulate, parietal and striatal regions. A novel permutation test indicated significant familial effects on variation of the MRI markers of inhibitory processing, supporting the candidacy of these brain structural systems as endophenotypes of OCD. In summary, structural variation in large-scale brain systems related to motor inhibitory control may mediate genetic risk for OCD, representing the first evidence for a neurocognitive endophenotype of OCD.
Familial, Inhibition, Multivoxel, Neuroimaging, Obsessive-compulsive
3223-3236
Menzies, Lara
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Achard, Sophie
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Chamberlain, Samuel R.
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Fineberg, Naomi
157dcac1-9fb2-4197-81f3-0167e1224f05
Chen, Chi Hua
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Del Campo, Natalia
16cfa0d6-12bd-41d1-8ae7-32e6eddc3f60
Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7
Bullmore, Ed
6e0f28a8-a70c-4391-a4f4-1172cdb6fd6b
December 2007
Menzies, Lara
06e7a774-9230-4e28-8862-df8d35f1b624
Achard, Sophie
90989c0a-982d-4fdd-838b-b975861535f3
Chamberlain, Samuel R.
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Fineberg, Naomi
157dcac1-9fb2-4197-81f3-0167e1224f05
Chen, Chi Hua
d522082b-3a68-4f16-a118-1252c6535ce9
Del Campo, Natalia
16cfa0d6-12bd-41d1-8ae7-32e6eddc3f60
Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7
Bullmore, Ed
6e0f28a8-a70c-4391-a4f4-1172cdb6fd6b
Menzies, Lara, Achard, Sophie, Chamberlain, Samuel R., Fineberg, Naomi, Chen, Chi Hua, Del Campo, Natalia, Sahakian, Barbara J., Robbins, Trevor W. and Bullmore, Ed
(2007)
Neurocognitive endophenotypes of obsessive-compulsive disorder.
Brain, 130 (12), .
(doi:10.1093/brain/awm205).
Abstract
Endophenotypes (intermediate phenotypes) are objective, heritable, quantitative traits hypothesized to represent genetic risk for polygenic disorders at more biologically tractable levels than distal behavioural and clinical phenotypes. It is theorized that endophenotype models of disease will help to clarify both diagnostic classification and aetiological understanding of complex brain disorders such as obsessive-compulsive disorder (OCD). To investigate endophenotypes in OCD, we measured brain structure using magnetic resonance imaging (MRI), and behavioural performance on a response inhibition task (Stop-Signal) in 31 OCD patients, 31 of their unaffected first-degree relatives, and 31 unrelated matched controls. Both patients and relatives had delayed response inhibition on the Stop-Signal task compared with healthy controls. We used a multivoxel analysis method (partial least squares) to identify large-scale brain systems in which anatomical variation was associated with variation in performance on the response inhibition task. Behavioural impairment on the Stop-Signal task, occurring predominantly in patients and relatives, was significantly associated with reduced grey matter in orbitofrontal and right inferior frontal regions and increased grey matter in cingulate, parietal and striatal regions. A novel permutation test indicated significant familial effects on variation of the MRI markers of inhibitory processing, supporting the candidacy of these brain structural systems as endophenotypes of OCD. In summary, structural variation in large-scale brain systems related to motor inhibitory control may mediate genetic risk for OCD, representing the first evidence for a neurocognitive endophenotype of OCD.
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Published date: December 2007
Keywords:
Familial, Inhibition, Multivoxel, Neuroimaging, Obsessive-compulsive
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Local EPrints ID: 492996
URI: http://eprints.soton.ac.uk/id/eprint/492996
ISSN: 0006-8950
PURE UUID: d85b582d-4da6-4d75-8c90-095f0368d08e
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Date deposited: 21 Aug 2024 17:12
Last modified: 22 Aug 2024 02:01
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Author:
Lara Menzies
Author:
Sophie Achard
Author:
Samuel R. Chamberlain
Author:
Naomi Fineberg
Author:
Chi Hua Chen
Author:
Natalia Del Campo
Author:
Barbara J. Sahakian
Author:
Trevor W. Robbins
Author:
Ed Bullmore
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