Is gray matter volume an intermediate phenotype for schizophrenia? A voxel-based morphometry study of patients with schizophrenia and their healthy siblings.
BACKGROUND
Shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover previously unidentified gray matter volume differences in patients with schizophrenia and their siblings with optimized voxel-based morphometry.


METHODS
We studied 169 patients with schizophrenia, 213 of their unaffected siblings, and 212 healthy volunteers from the Clinical Brain Disorders Branch/National Institute of Mental Health Genetic Study of Schizophrenia with magnetic resonance imaging.


RESULTS
Patients with schizophrenia had significant regional gray matter decreases in the frontal, temporal, and parietal cortices compared with healthy volunteers. Their unaffected siblings tended to share gray matter decreases in the medial frontal, superior temporal, and insular cortices, but these decreases were not significant after correction for multiple comparisons, even when we looked at a subgroup of siblings with a past history of mood disorder. As an exploratory analysis, we estimated heritability with regions of interest from the VBM analysis as well as from the hippocampus. Hippocampal volume was significantly correlated within sibling-pairs.


CONCLUSIONS
Our findings confirm and extend previous voxel-based morphometry analyses in ill subjects with schizophrenia. Furthermore, these data argue that although siblings might share some regional gray matter decreases with their affected siblings, the pattern of regional differences might be a weak intermediate phenotype for schizophrenia.
Honea
Robyn A
RA
Genes, Cognition and Psychosis Program, National Institute of Mental Health, Division of Intramural Research, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-1364, USA.
Meyer-Lindenberg
Andreas
A
Hobbs
Katherine B
KB
Pezawas
Lukas
L
Mattay
Venkata S
VS
Egan
Michael F
MF
Verchinski
Beth
B
Passingham
Richard E
RE
Weinberger
Daniel R
DR
Callicott
Joseph H
JH
D000328:Adult; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D004292:Dominance, Cerebral / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000235:genetics; D035781:Siblings; D012984:Software
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