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Nitin Gogtay, MD; Deanna Greenstein, PhD; Marge Lenane, MSW; Liv Clasen, PhD; Wendy Sharp, MSW; Pete Gochman, MA; Philip Butler, BS; Alan Evans, PhD; Judith Rapoport, MD

Arch Gen Psychiatry. 2007;64(7):772-780.

Context  Cortical gray matter (GM) loss is marked and progressive in childhood-onset schizophrenia (COS) during adolescence but becomes more circumscribed by early adulthood. Nonpsychotic siblings of COS probands could help evaluate whether the cortical GM abnormalities are familial/trait markers.

Objective  To map cortical development in nonpsychotic siblings of COS probands.

Design  Using an automated measurement and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in healthy full siblings (n = 52, 113 scans; age 8 through 28 years) of patients with COS, contrasting them with age-, sex-, and scan interval–matched healthy controls (n = 52, 108 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons.

Setting  An ongoing COS study at the National Institute of Mental Health.

Participants  Fifty-two healthy full siblings of patients with COS, aged 8 through 28 years, and 52 healthy controls.

Main Outcome Measures  Longitudinal trajectories of cortical GM development in healthy siblings of patients with COS compared with matched healthy controls and exploratory measure of the relationship between developmental GM trajectories and the overall functioning as defined by the Global Assessment Scale (GAS) score.

Results  Younger, healthy siblings of patients with COS showed significant GM deficits in the left prefrontal and bilateral temporal cortices and smaller deficits in the right prefrontal and inferior parietal cortices compared with the controls. These cortical deficits in siblings disappeared by age 20 years and the process of deficit reduction correlated with overall functioning (GAS scores) at the last scan.

Conclusions  Prefrontal and temporal GM loss in COS appears to be a familial/trait marker. Amelioration of regional GM deficits in healthy siblings was associated with higher global functioning (GAS scores), suggesting a relationship between brain plasticity and functional outcome for these nonpsychotic, nonspectrum siblings.

Author Affiliations: Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Drs Gogtay, Greenstein, Clasen, and Rapoport, Mss Lenane and Sharp, and Messrs Gochman and Butler); and Montreal Neurological Institute, Montreal, Quebec, Canada (Dr Evans).

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