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Sexually Dimorphic White Matter Geometry Abnormalities in Adolescent Onset Schizophrenia

1Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2Laboratory for Mathematics in Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3School of Psychology, University of New South Wales, Sydney, NSW, Australia.
4Gazzaley Laboratory, University of California at San Francisco, San Francisco, CA, USA.
5Department of Psychiatry, SANE POWIC, Warneford Hospital, University of Oxford, Oxford, UK.
Publication Date:
Cereb Cortex
Volume Number:
Issue Number:
Cereb Cortex. 2014 May;24(5):1389-96.
PubMed ID:
brain asymmetry, psychosis, schizophrenia, sex differences, white matter geometry
Appears in Collections:
G0500092/Medical Research Council/United Kingdom
P41 EB015902/EB/NIBIB NIH HHS/United States
P41 RR013218/RR/NCRR NIH HHS/United States
P50 MH080272/MH/NIMH NIH HHS/United States
R01 MH092862/MH/NIMH NIH HHS/United States
R01 MH050740/MH/NIMH NIH HHS/United States
R01 MH074794/MH/NIMH NIH HHS/United States
R01 MH082918/MH/NIMH NIH HHS/United States
R01 MH092862/MH/NIMH NIH HHS/United States
U54 EB005149/EB/NIBIB NIH HHS/United States
Generated Citation:
Savadjiev P., Whitford T.J., Hough M.E., Clemm von Hohenberg C., Bouix S., Westin C-F., Shenton M.E., Crow T.J., James A.C., Kubicki M. Sexually Dimorphic White Matter Geometry Abnormalities in Adolescent Onset Schizophrenia. Cereb Cortex. 2014 May;24(5):1389-96. PMID: 23307635. PMCID: PMC3977625.
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The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin C-F. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

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