Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings.
BACKGROUND
Schizophrenia is a highly heritable disorder associated with structural brain abnormalities. The aim of this study was to establish if the gene(s) for schizophrenia are associated with specific abnormalities of brain structure.


METHODS
Six sibships from multiple affected families were recruited. Each sibship consisted of one patient with schizophrenia, one "obligate carrier" without the disorder but with an affected child, and one "non-affected non-carrier". Such sibships are very rare, but present a powerful opportunity to separate the associations of genotype and phenotype. Obligates presumably have the gene(s) but not the disorder, affected siblings have both, whereas non-affected non-carrier siblings have neither.


METHODS
Brain MRI was conducted with a semiautomated region of interest analysis. The risk of false positive findings was reduced by collapsing brain regions and sides into five regions and comparing groups by repeated measures analysis of variance.


RESULTS
In terms of whole brain volumes and volumes of cortical structures, obligates resembled their non-affected non-carrier siblings, both groups having significantly greater volumes than their schizophrenic siblings (p=0.01 and p=0.04). Obligates also had significantly smaller ventricles than their schizophrenic siblings (p=0.03). However, with respect to the amygdalohippocampal complex, the obligates' brains resembled those of their schizophrenic siblings, both groups showing a significant reduction in volume when compared with their non-affected non-carrier siblings (p=0.001).


CONCLUSIONS
In the families studied, reductions in volumes of cortical structures and reductions in whole brain volume seem to be associated with the phenotype of schizophrenia. By contrast, reduced volume of the amygdalohippocampal complex seems to be associated with genetic risk for the disorder even in the absence of disease.
Steel
R M
RM
University of Edinburgh, Department of Psychiatry, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK.
Whalley
H C
HC
Miller
P
P
Best
J J K
JJ
Johnstone
E C
EC
Lawrie
S M
SM
D000328:Adult; D000679:Amygdala / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*