The impact of a Dysbindin schizophrenia susceptibility variant on fiber tract integrity in healthy individuals: a TBSS-based diffusion tensor imaging study.
Schizophrenia is a severe neuropsychiatric disorder with high heritability, though its exact etiopathogenesis is yet unknown. An increasing number of studies point to the importance of white matter anomalies in the pathophysiology of schizophrenia. While several studies have identified the impact of schizophrenia susceptibility gene variants on gray matter anatomy in both schizophrenia patients and healthy risk variant carriers, studies dealing with the impact of these gene variants on white matter integrity are still scarce. We here present a study on the effects of a Dysbindin schizophrenia susceptibility gene variant on fiber tract integrity in healthy young subjects. 101 subjects genotyped for Dysbindin-gene variant rs1018381, though without personal or first degree relative history of psychiatric disorders underwent diffusion tensor imaging (DTI), 83 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) analysis to delineate the major fiber tracts. Carriers of the minor allele T of the rs1018381 in the Dysbindin gene showed two clusters of reduced fractional anisotropy (FA) values in the perihippocampal region of the right temporal lobe compared to homozygote carriers of the major allele C. Clusters of increased FA values in T-allele carriers were found in the left prefrontal white matter, the right fornix, the right midbrain area, the left callosal body, the left cerebellum and in proximity of the right superior medial gyrus. Dysbindin has been implicated in neurite outgrowth and morphology. Impairments in anatomic connectivity as found associated with the minor Dysbindin allele in our study may result in increased risk for schizophrenia due to altered fiber tracts.
Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany. tnickl-jockschat@ukaachen.de
Thomas
T
Nickl-Jockschat
Tony
T
Stöcker
Valentin
V
Markov
Axel
A
Krug
Ruihuang
R
Huang
Frank
F
Schneider
Ute
U
Habel
Klaus
K
Zerres
Markus M
MM
Nöthen
Jens
J
Treutlein
Marcella
M
Rietschel
N Jon
NJ
Shah
Tilo
T
Kircher
D001921:Brain / Q000033:anatomy & histology*; D002352:Carrier Proteins / Q000235:genetics*; D056324:Diffusion Tensor Imaging / Q000379:methods; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000145:classification / Q000235:genetics; D055815:Young Adult
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins