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

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TitleHeritability of subcortical and limbic brain volume and shape in multiplex-multigenerational families with schizophrenia.
Publication TypeJournal Article
Year of Publication2015
AuthorsRoalf, DR, Vandekar, SN, Almasy, L, Ruparel, K, Satterthwaite, TD, Elliott, MA, Podell, J, Gallagher, S, Jackson, CT, Prasad, K, Wood, J, Pogue-Geile, MF, Nimgaonkar, VL, Gur, RC, Gur, RE
JournalBiol Psychiatry
Volume77
Issue2
Pagination137-46
Date Published2015 Jan 15
ISSN1873-2402
KeywordsAdult, Brain, Cohort Studies, Endophenotypes, European Continental Ancestry Group, Family, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Schizophrenia, United States
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.

DOI10.1016/j.biopsych.2014.05.009
Alternate JournalBiol Psychiatry
PubMed ID24976379
PubMed Central IDPMC4247350
Grant ListT32 MH019112 / MH / NIMH NIH HHS / United States
D43 TW009114 / TW / FIC NIH HHS / United States
T32 MH065218 / MH / NIMH NIH HHS / United States
R01MH042191 / MH / NIMH NIH HHS / United States
R01 MH084856 / MH / NIMH NIH HHS / United States
R01MH084856 / MH / NIMH NIH HHS / United States
R01 MH042191 / MH / NIMH NIH HHS / United States
R01 MH063480 / MH / NIMH NIH HHS / United States
R01MH063480 / MH / NIMH NIH HHS / United States
K01 MH102609 / MH / NIMH NIH HHS / United States
R01 MH061622 / MH / NIMH NIH HHS / United States
R01MH061622 / MH / NIMH NIH HHS / United States
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