Reduced occipital and prefrontal brain volumes in dysbindin-associated schizophrenia.
A three-marker C-A-T dysbindin haplotype identified by Williams et al (PMID: 15066891) is associated with increased risk for schizophrenia, decreased mRNA expression, poorer cognitive performance, and early sensory processing deficits. We investigated whether this same dysbindin risk haplotype was also associated with structural variation in the gray matter volume (GMV). Using voxel-based morphometry, whole-volume analysis revealed significantly reduced GMVs in both the right dorsolateral prefrontal and left occipital cortex, corresponding to the behavioral findings of impaired spatial working memory and EEG findings of impaired visual processing already reported. These data provide important evidence of the influence of dysbindin risk variants on brain structure, and suggest a possible mechanism by which disease risk is being increased.
Donohoe
Gary
G
Department of Psychiatry, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Dublin, Ireland. donoghug@tcd.ie
Frodl
Thomas
T
Morris
Derek
D
Spoletini
Ilaria
I
Cannon
Dara M
DM
Cherubini
Andrea
A
Caltagirone
Carlo
C
Bossù
Paola
P
McDonald
Colm
C
Gill
Michael
M
Corvin
Aiden P
AP
Spalletta
Gianfranco
G
D000328:Adult; D000704:Analysis of Variance; D001931:Brain Mapping; D002352:Carrier Proteins / Q000235:genetics*; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D004569:Electroencephalography / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D009778:Occipital Lobe / Q000473:pathology*; D017397:Prefrontal Cortex / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins