Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia

Gwenaëlle Douaud, Stephen Smith, Mark Jenkinson, Timothy Behrens, Heidi Johansen-Berg, John Vickers, Susan James, Natalie Voets, Kate Watkins, Paul M. Matthews, Anthony James

Research output: Contribution to journalArticle

445 Citations (Scopus)

Abstract

Adolescent-onset schizophrenia provides an exceptional opportunity to explore the neuropathology of schizophrenia free from the potential confounds of prolonged periods of medication and disease interactions with age-related neurodegeneration. Our aim was to investigate structural grey and white matter abnormalities in adolescent-onset schizophrenia. Whole-brain voxel-wise investigation of both grey matter topography and white matter integrity (Fractional Anisotropy) were carried out on 25 adolescent-onset schizophrenic patients and 25 healthy adolescents. We employed a refined voxel-based morphometry-like approach for grey matter analysis and the recently introduced method of tract-based spatial statistics (TBSS) for white matter analysis. Both kinds of studies revealed widespread abnormalities characterized by a lower fractional anisotropy neuroanatomically associated with localized reduced grey matter in the schizophrenic group. The grey matter changes can either be interpreted as the result of a locally reduced cortical thickness or as a manifestation of different patterns of gyrification. There was a widespread reduction of anisotropy in the white matter, especially in the corpus callosum. We speculate that the anisotropy changes relate to the functional changes in brain connectivity that are thought to play a central role in the clinical expression of the disease. The distribution of grey matter changes was consistent with clinical features of the disease. For example, grey and white matter abnormalities found in the Heschl's gyrus, the parietal operculum, left Broca's area and the left arcuate fasciculus (similar to previous findings in adult-onset schizophrenia) are likely to relate to functional impairments of language and auditory perception. In addition, in contrast to earlier studies, we found striking abnormalities in the primary sensorimotor and premotor cortices and in white matter tracts susbserving motor control (mainly the pyramidal tract). This novel finding suggests a new potential marker of altered white matter maturation specific to adolescent-onset schizophrenia. Together, our observations suggest that the neuropathology of adolescent-onset schizophrenia involves larger and widespread changes than in the adult form, consistent with the greater clinical severity.

LanguageEnglish
Pages2375-2386
Number of pages12
JournalBrain
Volume130
Issue number9
DOIs
Publication statusPublished - 1 Sep 2007

Keywords

  • Age of onset
  • Diffusion tensor imaging
  • Pyramidal tract
  • Schizophrenia
  • Voxel-based morphometry

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Douaud, G., Smith, S., Jenkinson, M., Behrens, T., Johansen-Berg, H., Vickers, J., ... James, A. (2007). Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. Brain, 130(9), 2375-2386. https://doi.org/10.1093/brain/awm184
Douaud, Gwenaëlle ; Smith, Stephen ; Jenkinson, Mark ; Behrens, Timothy ; Johansen-Berg, Heidi ; Vickers, John ; James, Susan ; Voets, Natalie ; Watkins, Kate ; Matthews, Paul M. ; James, Anthony. / Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. In: Brain. 2007 ; Vol. 130, No. 9. pp. 2375-2386.
@article{0686b43f8d644294b6ddf1816f38f826,
title = "Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia",
abstract = "Adolescent-onset schizophrenia provides an exceptional opportunity to explore the neuropathology of schizophrenia free from the potential confounds of prolonged periods of medication and disease interactions with age-related neurodegeneration. Our aim was to investigate structural grey and white matter abnormalities in adolescent-onset schizophrenia. Whole-brain voxel-wise investigation of both grey matter topography and white matter integrity (Fractional Anisotropy) were carried out on 25 adolescent-onset schizophrenic patients and 25 healthy adolescents. We employed a refined voxel-based morphometry-like approach for grey matter analysis and the recently introduced method of tract-based spatial statistics (TBSS) for white matter analysis. Both kinds of studies revealed widespread abnormalities characterized by a lower fractional anisotropy neuroanatomically associated with localized reduced grey matter in the schizophrenic group. The grey matter changes can either be interpreted as the result of a locally reduced cortical thickness or as a manifestation of different patterns of gyrification. There was a widespread reduction of anisotropy in the white matter, especially in the corpus callosum. We speculate that the anisotropy changes relate to the functional changes in brain connectivity that are thought to play a central role in the clinical expression of the disease. The distribution of grey matter changes was consistent with clinical features of the disease. For example, grey and white matter abnormalities found in the Heschl's gyrus, the parietal operculum, left Broca's area and the left arcuate fasciculus (similar to previous findings in adult-onset schizophrenia) are likely to relate to functional impairments of language and auditory perception. In addition, in contrast to earlier studies, we found striking abnormalities in the primary sensorimotor and premotor cortices and in white matter tracts susbserving motor control (mainly the pyramidal tract). This novel finding suggests a new potential marker of altered white matter maturation specific to adolescent-onset schizophrenia. Together, our observations suggest that the neuropathology of adolescent-onset schizophrenia involves larger and widespread changes than in the adult form, consistent with the greater clinical severity.",
keywords = "Age of onset, Diffusion tensor imaging, Pyramidal tract, Schizophrenia, Voxel-based morphometry",
author = "Gwena{\"e}lle Douaud and Stephen Smith and Mark Jenkinson and Timothy Behrens and Heidi Johansen-Berg and John Vickers and Susan James and Natalie Voets and Kate Watkins and Matthews, {Paul M.} and Anthony James",
year = "2007",
month = "9",
day = "1",
doi = "10.1093/brain/awm184",
language = "English",
volume = "130",
pages = "2375--2386",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "9",

}

Douaud, G, Smith, S, Jenkinson, M, Behrens, T, Johansen-Berg, H, Vickers, J, James, S, Voets, N, Watkins, K, Matthews, PM & James, A 2007, 'Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia', Brain, vol. 130, no. 9, pp. 2375-2386. https://doi.org/10.1093/brain/awm184

Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. / Douaud, Gwenaëlle; Smith, Stephen; Jenkinson, Mark; Behrens, Timothy; Johansen-Berg, Heidi; Vickers, John; James, Susan; Voets, Natalie; Watkins, Kate; Matthews, Paul M.; James, Anthony.

In: Brain, Vol. 130, No. 9, 01.09.2007, p. 2375-2386.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia

AU - Douaud, Gwenaëlle

AU - Smith, Stephen

AU - Jenkinson, Mark

AU - Behrens, Timothy

AU - Johansen-Berg, Heidi

AU - Vickers, John

AU - James, Susan

AU - Voets, Natalie

AU - Watkins, Kate

AU - Matthews, Paul M.

AU - James, Anthony

PY - 2007/9/1

Y1 - 2007/9/1

N2 - Adolescent-onset schizophrenia provides an exceptional opportunity to explore the neuropathology of schizophrenia free from the potential confounds of prolonged periods of medication and disease interactions with age-related neurodegeneration. Our aim was to investigate structural grey and white matter abnormalities in adolescent-onset schizophrenia. Whole-brain voxel-wise investigation of both grey matter topography and white matter integrity (Fractional Anisotropy) were carried out on 25 adolescent-onset schizophrenic patients and 25 healthy adolescents. We employed a refined voxel-based morphometry-like approach for grey matter analysis and the recently introduced method of tract-based spatial statistics (TBSS) for white matter analysis. Both kinds of studies revealed widespread abnormalities characterized by a lower fractional anisotropy neuroanatomically associated with localized reduced grey matter in the schizophrenic group. The grey matter changes can either be interpreted as the result of a locally reduced cortical thickness or as a manifestation of different patterns of gyrification. There was a widespread reduction of anisotropy in the white matter, especially in the corpus callosum. We speculate that the anisotropy changes relate to the functional changes in brain connectivity that are thought to play a central role in the clinical expression of the disease. The distribution of grey matter changes was consistent with clinical features of the disease. For example, grey and white matter abnormalities found in the Heschl's gyrus, the parietal operculum, left Broca's area and the left arcuate fasciculus (similar to previous findings in adult-onset schizophrenia) are likely to relate to functional impairments of language and auditory perception. In addition, in contrast to earlier studies, we found striking abnormalities in the primary sensorimotor and premotor cortices and in white matter tracts susbserving motor control (mainly the pyramidal tract). This novel finding suggests a new potential marker of altered white matter maturation specific to adolescent-onset schizophrenia. Together, our observations suggest that the neuropathology of adolescent-onset schizophrenia involves larger and widespread changes than in the adult form, consistent with the greater clinical severity.

AB - Adolescent-onset schizophrenia provides an exceptional opportunity to explore the neuropathology of schizophrenia free from the potential confounds of prolonged periods of medication and disease interactions with age-related neurodegeneration. Our aim was to investigate structural grey and white matter abnormalities in adolescent-onset schizophrenia. Whole-brain voxel-wise investigation of both grey matter topography and white matter integrity (Fractional Anisotropy) were carried out on 25 adolescent-onset schizophrenic patients and 25 healthy adolescents. We employed a refined voxel-based morphometry-like approach for grey matter analysis and the recently introduced method of tract-based spatial statistics (TBSS) for white matter analysis. Both kinds of studies revealed widespread abnormalities characterized by a lower fractional anisotropy neuroanatomically associated with localized reduced grey matter in the schizophrenic group. The grey matter changes can either be interpreted as the result of a locally reduced cortical thickness or as a manifestation of different patterns of gyrification. There was a widespread reduction of anisotropy in the white matter, especially in the corpus callosum. We speculate that the anisotropy changes relate to the functional changes in brain connectivity that are thought to play a central role in the clinical expression of the disease. The distribution of grey matter changes was consistent with clinical features of the disease. For example, grey and white matter abnormalities found in the Heschl's gyrus, the parietal operculum, left Broca's area and the left arcuate fasciculus (similar to previous findings in adult-onset schizophrenia) are likely to relate to functional impairments of language and auditory perception. In addition, in contrast to earlier studies, we found striking abnormalities in the primary sensorimotor and premotor cortices and in white matter tracts susbserving motor control (mainly the pyramidal tract). This novel finding suggests a new potential marker of altered white matter maturation specific to adolescent-onset schizophrenia. Together, our observations suggest that the neuropathology of adolescent-onset schizophrenia involves larger and widespread changes than in the adult form, consistent with the greater clinical severity.

KW - Age of onset

KW - Diffusion tensor imaging

KW - Pyramidal tract

KW - Schizophrenia

KW - Voxel-based morphometry

UR - http://www.scopus.com/inward/record.url?scp=34548262723&partnerID=8YFLogxK

U2 - 10.1093/brain/awm184

DO - 10.1093/brain/awm184

M3 - Article

VL - 130

SP - 2375

EP - 2386

JO - Brain

T2 - Brain

JF - Brain

SN - 0006-8950

IS - 9

ER -

Douaud G, Smith S, Jenkinson M, Behrens T, Johansen-Berg H, Vickers J et al. Anatomically related grey and white matter abnormalities in adolescent-onset schizophrenia. Brain. 2007 Sep 1;130(9):2375-2386. https://doi.org/10.1093/brain/awm184