Basal ganglia shape abnormalities in the unaffected siblings of schizophrenia patients.
BACKGROUND
Abnormalities of basal ganglia structure in schizophrenia have been attributed to the effects of antipsychotic drugs. Our aim was to test the hypothesis that abnormalities of basal ganglia structure are intrinsic features of schizophrenia by assessing basal ganglia volume and shape in the unaffected siblings of schizophrenia subjects.


METHODS
The study involved 25 pairs of schizophrenia subjects and their unaffected siblings and 40 pairs of healthy control subjects and their siblings. Large-deformation, high-dimensional brain mapping was used to obtain surface representations of the caudate, putamen, and globus pallidus. Surfaces were derived from transformations of anatomic templates, and shapes were analyzed using reduced-dimensional measures of surface variability (i.e., principal components and canonical analysis). Canonical functions were derived using schizophrenia and control groups and were then used to compare shapes in the sibling groups. To visualize shape differences, maps of the estimated surface displacement between groups were created.


RESULTS
In the caudate, putamen, and globus pallidus, the degree of shape abnormality observed in the siblings of the schizophrenia subjects was intermediate between the schizophrenia and control subjects. In the schizophrenia subjects, significant correlations were observed between measures of caudate, putamen, and globus pallidus structure and the selected measures of lifetime psychopathology.


CONCLUSIONS
Attenuated abnormalities of basal ganglia structure are present in the unaffected siblings of schizophrenia subjects. This finding implies that basal ganglia structural abnormalities observed in subjects with schizophrenia are at least in part an intrinsic feature of the illness.
Mamah
Daniel
D
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA. mamahd@psychiatry.wustl.edu
Harms
Michael P
MP
Wang
Lei
L
Barch
Deanna
D
Thompson
Paul
P
Kim
Jaeyun
J
Miller
Michael I
MI
Csernansky
John G
JG
D000293:Adolescent; D000328:Adult; D001479:Basal Ganglia / Q000002:abnormalities* / Q000473:pathology; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000002:abnormalities / Q000473:pathology; D004292:Dominance, Cerebral / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005917:Globus Pallidus / Q000002:abnormalities / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D011699:Putamen / Q000002:abnormalities / Q000473:pathology; D012016:Reference Values; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology