Volumetric White Matter Abnormalities in First-Episode Schizophrenia: A Longitudinal, Tensor-Based Morphometry Study
Abstract
Objective: While schizophrenia has long been considered a disorder of brain connectivity, few studies have investigated white matter abnormalities in patients with first-episode schizophrenia, and even fewer studies have investigated whether there is progressive white matter pathology in the disease. Method: The authors obtained a T1-weighted structural magnetic resonance imaging (MRI) scan on 41 patients with first-episode schizophrenia. These first-episode schizophrenia patients were analyzed relative to 47 age- and sex-matched healthy comparison subjects who also underwent an MRI scan. Of the baseline participants, 25 first-episode schizophrenia patients and 26 comparison subjects returned 2 to 3 years later for a follow-up scan. To identify regional volumetric white matter differences between the two groups at baseline, voxel-based morphometry in statistical parametric mapping-2 (SPM2) was used, while tensor-based morphometry was used to identify the longitudinal changes over the follow-up interval. Results: The first-episode schizophrenia patients exhibited volumetric deficits in the white matter of the frontal and temporal lobes at baseline, as well as volumetric increases in the white matter of the frontoparietal junction bilaterally. Furthermore, these first-episode schizophrenia patients lost considerably more white matter over the follow-up interval relative to comparison subjects in the middle and inferior temporal cortex bilaterally. Conclusions: These results indicate that patients with schizophrenia exhibit white matter abnormalities at the time of their first presentation of psychotic symptoms to mental health services and that these abnormalities degenerate further over the initial years of illness. Given the role that white matter plays in neural communication, the authors suggest that these white matter abnormalities may be a cause of the dysfunctional neural connectivity that has been proposed to underlie the symptoms of schizophrenia.
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Patients with schizophrenia exhibit structural abnormalities in the cerebral white matter.
“After more than 2 decades of neuroimaging research, it is now well established that patients with schizophrenia exhibit structural abnormalities in the cerebral white matter.”
From Schizophrenia, myelination, and delayed corollary discharges: a hypothesis (2012) · cites this paper as [20]
Schizophrenia patients exhibit myelin-specific abnormalities including reduced numbers of oligodendrocytes, irregular myelin microstructure, and subnormal expression of myelin-related genes.
“When combined with the fact that schizophrenia patients exhibit a range of myelin-specific abnormalities-including reduced numbers of oligodendrocytes, 19 irregular myelin microstructure, 20 and subnormal expression of myelin-related genes 44”
From Schizophrenia, myelination, and delayed corollary discharges: a hypothesis (2012) · cites this paper as [20]
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- Authors
- Whitford, T. J., Grieve, S. M., Farrow, T. F. D., Gomes, L., Brennan, J., Harris, A. W. F., Gordon, E., & Williams, L. M.
- Affiliations
- Westmead Hospital (AU)
- Venue
- American Journal of Psychiatry
- Published
- 2007-07
- Volume
- 164
- Issue
- 7
- Pages
- 1082-1089
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2006061154
- Cited by
- 99
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2020: 3 · 2019: 9 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 5 · 2013: 6 · 2012: 9
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- first-episode schizophrenia, white matter abnormalities, white matter volume, longitudinal brain changes, frontal lobe, temporal lobe, inferior temporal cortex, neuronal connectivity, disease progression
- MeSH terms
- Adolescent, Adult, Age Factors, Atrophy, Brain, Female, Follow-Up Studies, Humans, Functional Laterality, Longitudinal Studies, Magnetic Resonance Imaging, Male, Models, Neurological, Neural Pathways, Schizophrenia, Sex Factors, Cohort Studies, Disease Progression
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