title: Delayed white matter growth trajectory in young nonpsychotic siblings of patients with childhood-onset schizophrenia.
abstract: CONTEXT Nonpsychotic siblings of patients with childhood-onset schizophrenia (COS) share cortical gray matter abnormalities with their probands at an early age; these normalize by the time the siblings are aged 18 years, suggesting that the gray matter abnormalities in schizophrenia could be an age-specific endophenotype. Patients with COS also show significant white matter (WM) growth deficits, which have not yet been explored in nonpsychotic siblings. OBJECTIVE To study WM growth differences in nonpsychotic siblings of patients with COS. DESIGN Longitudinal (5-year) anatomic magnetic resonance imaging study mapping WM growth using a novel tensor-based morphometry analysis. SETTING National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS Forty-nine healthy siblings of patients with COS (mean [SD] age, 16.1 [5.3] years; 19 male, 30 female) and 57 healthy persons serving as controls (age, 16.9 [5.3] years; 29 male, 28 female). INTERVENTION Magnetic resonance imaging. MAIN OUTCOME MEASURE White matter growth rates. RESULTS We compared the WM growth rates in 3 age ranges. In the youngest age group (7 to <14 years), we found a significant difference in growth rates, with siblings of patients with COS showing slower WM growth rates in the parietal lobes of the brain than age-matched healthy controls (false discovery rate, q = 0.05; critical P = .001 in the bilateral parietal WM; a post hoc analysis identified growth rate differences only on the left side, critical P = .004). A growth rate difference was not detectable at older ages. In 3-dimensional maps, growth rates in the siblings even appeared to surpass those of healthy individuals at later ages, at least locally in the brain, but this effect did not survive a multiple comparisons correction. CONCLUSIONS In this first longitudinal study of nonpsychotic siblings of patients with COS, the siblings showed early WM growth deficits, which normalized with age. As reported before for gray matter, WM growth may also be an age-specific endophenotype that shows compensatory normalization with age.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
authors.forename: Xue
authors.initials: X
authors.lastname: Hua
authors.forename: Reva
authors.initials: R
authors.lastname: Stidd
authors.forename: Christina P
authors.initials: CP
authors.lastname: Boyle
authors.forename: Suh
authors.initials: S
authors.lastname: Lee
authors.forename: Brian
authors.initials: B
authors.lastname: Weisinger
authors.forename: Alex
authors.initials: A
authors.lastname: Chavez
authors.forename: Jay N
authors.initials: JN
authors.lastname: Giedd
authors.forename: Liv
authors.initials: L
authors.lastname: Clasen
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001931:Brain Mapping / Q000379:methods; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D056784:Leukoencephalopathies / Q000175:diagnosis* / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D009929:Organ Size; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics*; D012565:Schizophrenic Psychology; D055815:Young Adult