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Cited by 149Schizophrenia research and treatmentAdvanced Neuroimaging Techniques and ApplicationsFunctional Brain Connectivity Studies

Mean diffusivity and fractional anisotropy as indicators of disease and genetic liability to schizophrenia

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Clark, Kristi A., Nuechterlein, Keith H., Asarnow, Robert F., Hamilton, Liberty S., Phillips, Owen R., Hageman, Nathan S., Woods, Roger P., Alger, Jeffry R. +2 more·2011·Journal of Psychiatric Research
DOI 10.1016/j.jpsychires.2011.01.006PMC PMC3109158
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Abstract

The goals of this study were to first determine whether the fractional anisotropy (FA) and mean diffusivity (MD) of major white matter pathways associate with schizophrenia, and secondly to characterize the extent to which differences in these metrics might reflect a genetic predisposition to schizophrenia. Differences in FA and MD were identified using a comprehensive atlas-based tract mapping approach using diffusion tensor imaging and high-resolution structural data from 35 patients, 28 unaffected first-degree relatives of patients, 29 community controls, and 14 first-degree relatives of controls. Schizophrenia patients had significantly higher MD in the following tracts compared to controls: the right anterior thalamic radiations, the forceps minor, the bilateral inferior fronto-occipital fasciculus (IFO), the temporal component of the left superior longitudinal fasciculus (tSLF), and the bilateral uncinate. FA showed schizophrenia effects and a linear relationship to genetic liability (represented by schizophrenia patients, first-degree relatives, and controls) for the bilateral IFO, the left inferior longitudinal fasciculus (ILF), and the left tSLF. Diffusion tensor imaging studies have previously identified white matter abnormalities in all three of these tracts in schizophrenia; however, this study is the first to identify a significant genetic liability. Thus, FA of these three tracts may serve as biomarkers for studies seeking to identify how genes influence brain structure predisposing to schizophrenia. However, differences in FA and MD in frontal and temporal white matter pathways may be additionally driven by state variables that involve processes associated with the disease.

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  • Among familial high-risk schizophrenia studies, only a minority find cingulum changes, with other structures more often affected.

    “Only a minority of these familial studies find cingulum changes, with other structures more often affected (e.g., Clark et al., 2011; Hoptman et al., 2008; Karlsgodt et al., 2009; Maniega et al., 2008).”

    From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as Clark et al., 2011

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Cited by

Sorted by citations

Authors
Clark, K. A., Nuechterlein, K. H., Asarnow, R. F., Hamilton, L. S., Phillips, O. R., Hageman, N. S., Woods, R. P., Alger, J. R., Toga, A. W., & Narr, K. L.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Clark, Kristi A.
ORCID
Venue
Journal of Psychiatric Research
Publisher
Elsevier BV
Published
2011-07
Volume
45
Issue
7
Pages
980-988
ISSN
0022-3956 (ISSN-L)
DOI
10.1016/j.jpsychires.2011.01.006
PMC
PMC3109158
OpenAlex
W2122362881
Cited by
149
References
8
Citations by year
2026: 8 · 2025: 3 · 2024: 9 · 2023: 14 · 2022: 17 · 2021: 16 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 12 · 2014: 7 · 2013: 12 · 2012: 4
FWCI
5.28
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Psychiatric Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (MH037705, MH-066286, MH073990, K01MH073990, R01MH037705, P50MH066286, MH049716, R01MH049716)
  • National Center for Research Resources (P41RR013642, U54RR021813)
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
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Keywords
schizophrenia, mean diffusivity, fractional anisotropy, white matter, genetic susceptibility, first-degree relatives, diffusion tensor imaging, tractography, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, thalamic radiation, forceps minor, biomarkers, brain structure
MeSH terms
Adolescent, Adult, Brain, Dominance, Cerebral, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Neural Pathways, Brief Psychiatric Rating Scale, Reference Values, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Genetic Predisposition to Disease, Diffusion Magnetic Resonance Imaging, Young Adult

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