Delayed white matter growth trajectory in young nonpsychotic siblings of patients with childhood-onset schizophrenia

Nitin Gogtay, Xue Hua, Reva Stidd, Christina P. Boyle, Suh Lee, Brian Weisinger, Alex Chavez, Jay N. Giedd, Liv Clasen, Arthur W. Toga, Judith L. Rapoport, Paul M. Thompson

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


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.

Original languageEnglish
Pages (from-to)875-884
Number of pages10
JournalArchives of General Psychiatry
Issue number9
StatePublished - Sep 2012
Externally publishedYes


Dive into the research topics of 'Delayed white matter growth trajectory in young nonpsychotic siblings of patients with childhood-onset schizophrenia'. Together they form a unique fingerprint.

Cite this