title: Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia.
abstract: Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia.
authors.affiliation: University of California San Francisco, United States. Electronic address: dwagshal@memory.ucsf.edu.
authors.forename: Dana
authors.initials: D
authors.lastname: Wagshal
authors.affiliation: University of CA Los Angeles, United States.
authors.forename: Barbara Jean
authors.initials: BJ
authors.lastname: Knowlton
authors.affiliation: University of CA, Berkeley, United States.
authors.forename: Jessica Rachel
authors.initials: JR
authors.lastname: Cohen
authors.affiliation: David Geffen School of Medicine , University of CA, Los Angeles, United States.
authors.forename: Susan Yost
authors.initials: SY
authors.lastname: Bookheimer
authors.affiliation: David Geffen School of Medicine , University of CA, Los Angeles, United States.
authors.forename: Robert Martin
authors.initials: RM
authors.lastname: Bilder
authors.affiliation: David Geffen School of Medicine , University of CA, Los Angeles, United States.
authors.forename: Vindia Gisela
authors.initials: VG
authors.lastname: Fernandez
authors.affiliation: David Geffen School of Medicine , University of CA, Los Angeles, United States.
authors.forename: Robert Franklin
authors.initials: RF
authors.lastname: Asarnow
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001921:Brain / Q000002:abnormalities*; D002648:Child; D058068:Endophenotypes; D066128:Gray Matter / Q000002:abnormalities*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007858:Learning; D008279:Magnetic Resonance Imaging; D009929:Organ Size; D011581:Psychological Tests; D012559:Schizophrenia; D035781:Siblings / Q000523:psychology*
keywords: Cognitive skill learning; Schizophrenia; Striatal dysfunction; Structural abnormalities; VBM