title: Normalization of cortical gray matter deficits in nonpsychotic siblings of patients with childhood-onset schizophrenia.
abstract: OBJECTIVE
  Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to "normalize" by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls.
  
  
  METHODS
  Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval-matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons.
  
  
  RESULTS
  As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17.
  
  
  CONCLUSIONS
  Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health/NIH, 10 Center Drive, Bethesda, MD 20892, USA. mattaia@mail.nih.gov
authors.forename: Anand A
authors.initials: AA
authors.lastname: Mattai
authors.forename: Brian
authors.initials: B
authors.lastname: Weisinger
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.forename: Reva
authors.initials: R
authors.lastname: Stidd
authors.forename: Liv
authors.initials: L
authors.lastname: Clasen
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller
authors.forename: Julia W
authors.initials: JW
authors.lastname: Tossell
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D058068:Endophenotypes; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D012561:Schizophrenia, Childhood / Q000453:epidemiology* / Q000235:genetics; D035781:Siblings / Q000523:psychology*; D014481:United States / Q000453:epidemiology