Abstract
Background
Brain abnormalities of subcortical and limbic nuclei are common in patients with schizophrenia,
and variation in these structures is considered a putative endophenotype for the disorder.
Multiplex-multigenerational families with schizophrenia provide an opportunity to
investigate the impact of shared genetic ancestry, but these families have not been
previously examined to study structural brain abnormalities. We estimate the heritability
of subcortical and hippocampal brain volumes in multiplex-multigenerational families
and the heritability of subregions using advanced shape analysis.
Methods
The study comprised 439 participants from two sites who underwent 3T structural magnetic
resonance imaging. The participants included 190 European-Americans from 32 multiplex-multigenerational
families with schizophrenia and 249 healthy comparison subjects. Subcortical and hippocampal
volume and shape were measured in 14 brain structures. Heritability was estimated
for volume and shape.
Results
Volume and shape were heritable in families. Estimates of heritability in subcortical
and limbic volumes ranged from .45 in the right hippocampus to .84 in the left putamen.
The shape of these structures was heritable (range, .40–.49), and specific subregional
shape estimates of heritability tended to exceed heritability estimates of volume
alone.
Conclusions
These results demonstrate that volume and shape of subcortical and limbic brain structures
are potential endophenotypic markers in schizophrenia. The specificity obtained using
shape analysis may improve selection of imaging phenotypes that better reflect the
underlying neurobiology. Our findings can aid in the identification of specific genetic
targets that affect brain structure and function in schizophrenia.
Keywords
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Article info
Publication history
Published online: May 27, 2014
Accepted:
May 21,
2014
Received in revised form:
April 25,
2014
Received:
September 26,
2013
Identification
Copyright
© 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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