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 (+2 others)
2009 Human Brain Mapping  
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.
more » ... 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 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 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.
doi:10.1002/hbm.20806 pmid:19449336 pmcid:PMC3176807 fatcat:hrqchakz5vbpncounramiciqoa