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Biol Psychiatry. 2015 Jan 15;77(2):137-46. doi: 10.1016/j.biopsych.2014.05.009. Epub 2014 May 28.

Heritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia.

Author information

1
Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: roalf@upenn.edu.
2
Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
3
Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas.
4
Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
5
Departments of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
6
Departments of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.; Departments of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.
7
Departments of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.; Departments of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.

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:

Endophenotypes; Heritability; Hippocampus; Neuroimaging-genetics; Schizophrenia; Structural MRI

Comment in

PMID:
24976379
PMCID:
PMC4247350
DOI:
10.1016/j.biopsych.2014.05.009
[Indexed for MEDLINE]
Free PMC Article
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