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Heritability of Subcortical and Limbic Brain Volume and Shape in Multiplex-Multigenerational Families with Schizophrenia

      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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          The biggest challenge for psychiatry today is the need to reveal and verify the essential pathologies of psychiatric syndromes, including discovering relevant molecular, synaptic, and circuit formulations of biologically based psychiatric diseases. Any demonstrated pathology that reflects the biology of a facet or characterizes a subgroup of a psychiatric syndrome would be an important target. Medical scientists must have asked this same question in the early 1900s when they were grasping for modern medicine handles on illness manifestations such as fever and dropsy (morbid edema).
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