title: 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.
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. Electronic address: roalf@upenn.edu.
authors: David R
authors: DR
authors: Roalf
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Simon N
authors: SN
authors: Vandekar
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas.
authors: Laura
authors: L
authors: Almasy
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Kosha
authors: K
authors: Ruparel
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Theodore D
authors: TD
authors: Satterthwaite
authors: 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.
authors: Mark A
authors: MA
authors: Elliott
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Jamie
authors: J
authors: Podell
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Sean
authors: S
authors: Gallagher
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Chad T
authors: CT
authors: Jackson
authors: Departments of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Konasale
authors: K
authors: Prasad
authors: Neuropsychiatry Section, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Joel
authors: J
authors: Wood
authors: Departments of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.; Departments of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Michael F
authors: MF
authors: Pogue-Geile
authors: Departments of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.; Departments of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Vishwajit L
authors: VL
authors: Nimgaonkar
authors: 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.
authors: Ruben C
authors: RC
authors: Gur
authors: 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.
authors: Raquel E
authors: RE
authors: Gur
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D015331:Cohort Studies; D058068:Endophenotypes; D005190:Family; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D014481:United States; D044465:White People
keywords: Endophenotypes; Heritability; Hippocampus; Neuroimaging-genetics; Schizophrenia; Structural MRI