title: Sexual dimorphic abnormalities in white matter geometry common to schizophrenia and non-psychotic high-risk subjects: Evidence for a neurodevelopmental risk marker?
abstract: The characterization of neurodevelopmental aspects of brain alterations require neuroimaging methods that reflect correlates of neurodevelopment, while being robust to other progressive pathological processes. Newly developed neuroimaging methods for measuring geometrical features of the white matter fall exactly into this category. Our recent work shows that such features, measured in the anterior corpus callosum in diffusion MRI data, correlate with psychosis symptoms in patients with adolescent onset schizophrenia and subside a reversal of normal sexual dimorphism. Here, we test the hypothesis that similar developmental deviations will also be present in nonpsychotic subjects at familial high risk (FHR) for schizophrenia, due to genetic predispositions. Demonstrating such changes would provide a strong indication of neurodevelopmental deviation extant before, and independent of pathological changes occurring after disease onset. We examined the macrostructural geometry of corpus callosum white matter in diffusion MRI data of 35 non-psychotic subjects with genetic (familial) risk for schizophrenia, and 26 control subjects, both male and female. We report a reversal of normal sexual dimorphism in callosal white matter geometry consistent with recent results in adolescent onset schizophrenia. This pattern may be indicative of an error in neurogenesis and a possible trait marker of schizophrenia.
authors.affiliation: Department of Psychiatry, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Savadjiev
authors.affiliation: Massachusetts Mental Health Center, Division of Public Psychiatry, Boston, Massachusetts.|Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.affiliation: Massachusetts Mental Health Center, Division of Public Psychiatry, Boston, Massachusetts.|Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Heidi
authors.initials: H
authors.lastname: Thermenos
authors.affiliation: Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Matcheri
authors.initials: M
authors.lastname: Keshavan
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Whitfield-Gabrieli
authors.affiliation: SANE POWIC, University Department of Psychiatry, Warneford Hospital, Oxford, United Kingdom.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Crow
authors.affiliation: Department of Psychiatry, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry and Radiology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts.
authors.forename: Marek
authors.initials: M
authors.lastname: Kubicki
mesh_terms: D000328:Adult; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000473:pathology*; D012559:Schizophrenia / Q000473:pathology*; D012727:Sex Characteristics; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
keywords: familial risk; neurodevelopment; schizophrenia; sexual dimorphism; white matter geometry