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. 2015 Feb;161(2-3):345-50.
doi: 10.1016/j.schres.2014.12.006. Epub 2014 Dec 22.

Cognitive Correlates of Gray Matter Abnormalities in Adolescent Siblings of Patients With Childhood-Onset Schizophrenia

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Cognitive Correlates of Gray Matter Abnormalities in Adolescent Siblings of Patients With Childhood-Onset Schizophrenia

Dana Wagshal et al. Schizophr Res. .
Free PMC article


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.

Keywords: Cognitive skill learning; Schizophrenia; Striatal dysfunction; Structural abnormalities; VBM.

Conflict of interest statement

Conflict of interest

None of the authors declares any conflict of interest.


Fig. 1
Fig. 1
The WPT task. Participants were told to predict the weather (sun or rain) based on cues. On every trial between 1 and 3 cues (out of 4 possibilities) could appear, yielding 14 possible combinations. The cues were probabilistically related to the outcomes. The association of the different cues with different probabilities was randomized across participants.
Fig. 2
Fig. 2
Brain regions that showed a significant correlation with late WPT performance. T-statistical maps were corrected for multiple comparisons with familywise error (FWE) correction and Threshold-Free Cluster Enhancement (TFCE) at p < 0.05. A = positive correlation between controls and late WPT performance in the right superior frontal gyrus, B = positive correlation between COS siblings and late WPT performance in the right cerebellum.

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