title: DTNBP1 is associated with imaging phenotypes in schizophrenia.
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 sub-compartments. 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.
authors.affiliation: Laboratory of Neuro Imaging and Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. narr@loni.ucla.edu
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
authors.forename: Philip R
authors.initials: PR
authors.lastname: Szeszko
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.forename: Roger P
authors.initials: RP
authors.lastname: Woods
authors.forename: Liberty S
authors.initials: LS
authors.lastname: Hamilton
authors.forename: Owen
authors.initials: O
authors.lastname: Phillips
authors.forename: Delbert
authors.initials: D
authors.lastname: Robinson
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burdick
authors.forename: Pamela
authors.initials: P
authors.lastname: DeRosse
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.forename: Arthur W
authors.initials: AW
authors.lastname: Toga
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bilder
mesh_terms: D000328:Adult; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008959:Models, Neurological; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins