DTNBP1 is associated with imaging phenotypes in schizophrenia

Katherine L. Narr, Philip R. Szeszko, Todd Lencz, Roger P. Woods, Liberty S. Hamilton, Owen Phillips, Delbert Robinson, Katherine E. Burdick, Pamela DeRosse, Raju Kucherlapati, Paul M. Thompson, Arthur W. Toga, Anil K. Malhotra, Robert M. Bilder

Research output: Contribution to journalArticlepeer-review

Abstract

Dystrobrevin binding protein 1 (DTNBP1) has been identified as putative schizophrenia susceptibility gene, but it remains unknown whether polymorphisms relate to altered cerebral structure. We examined relationships between a previously implicated DTNBP1 risk variant [P1578] and global and segmented brain tissue volumes and regional cortical thickness in schizophrenia (n = 62; 24 risk carriers) and healthy subjects (n = 42; 11 risk carriers), across ethnic groups and within Caucasians. Schizophrenia patients showed similar brain volumes, but significantly reduced brain-size adjusted gray matter and CSF volumes and cortical thinning in a widespread neocortical distribution compared to controls. DTNBP1 risk was found associated with reduced brain volume, but not with tissue subcompartments. Cortical thickness, which was weakly associated with brain size, showed regional variations in association with genetic risk, although effects were dominated by highly significant genotype by diagnosis interactions over broad areas of cortex. Risk status was found associated with regional cortical thinning in patients, particularly in temporal networks, but with thickness increases in controls. DTNBP1 effects for brain volume and cortical thickness appear driven by different neurobiological processes. Smaller brain volumes observed in risk carriers may relate to previously reported DTNBP1/cognitive function relationships irrespective of diagnosis. Regional cortical thinning in patient, but not in control risk carriers, may suggest that DTNBP1 interacts with other schizophrenia-related risk factors to affect laminar thickness. Alternatively, DTNBP1 may influence neural processes for which individuals with thicker cortex are less vulnerable. Although DTNBP1 relates to cortical thinning in schizophrenia, morphological changes in the disorder are influenced by additional genetic and/or environmental factors.

Original languageEnglish
Pages (from-to)3783-3794
Number of pages12
JournalHuman Brain Mapping
Volume30
Issue number11
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Brain structure
  • Cortical thickness
  • Dysbindin
  • Genetic marker
  • Gray matter
  • Magnetic resonance imaging (MRI)
  • Morphology
  • Polymorphism

ASJC Scopus subject areas

  • Anatomy
  • Clinical Neurology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Radiological and Ultrasound Technology

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