title: Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity.
abstract: G72 (syn. DAOA, D-amino acid oxidase activator) is a susceptibility gene for both schizophrenia and bipolar disorder. Diffusion tensor imaging studies hint at changes in fiber tract integrity in both disorders. We aimed to investigate whether a G72 susceptibility haplotype causes changes in fiber tract integrity in young healthy subjects. We compared fractional anisotropy in 47 subjects that were either homozygous for the M23/M24 risk haplotype (n = 20) or homozygous for M23(rs3918342)/M24(rs1421292) wild type (n = 27) using diffusion tensor imaging with 3 T. Tract-based spatial statistics, a method especially developed for diffusion data analysis, was used to delineate the major fiber tracts. We found clusters of increased FA values in homozygous risk haplotype carriers in the right periinsular region and in the right inferior parietal lobe (IPL). We did not find clusters indicating decreased FA values. The insula and the IPL have been implicated in both schizophrenia and bipolar pathophysiology. Increased FA values might reflect changes in dendritic morphology as previously described by in vitro studies. These findings further corroborate the hypothesis that a shared gene pool between schizophrenia and bipolar disorder might lead to neuroanatomic changes that confer an unspecific vulnerability for both disorders.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelsstrasse-30, 52074, Aachen, Germany, tnickl-jockschat@ukaachen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nickl-Jockschat
authors.forename: Tony
authors.initials: T
authors.lastname: Stöcker
authors.forename: Axel
authors.initials: A
authors.lastname: Krug
authors.forename: Valentin
authors.initials: V
authors.lastname: Markov
authors.forename: Ivan I
authors.initials: II
authors.lastname: Maximov
authors.forename: Ruiwang
authors.initials: R
authors.lastname: Huang
authors.forename: Frank
authors.initials: F
authors.lastname: Schneider
authors.forename: Ute
authors.initials: U
authors.lastname: Habel
authors.forename: Simon B
authors.initials: SB
authors.lastname: Eickhoff
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: N
authors.initials: N
authors.lastname: Jon Shah
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
mesh_terms: D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000033:anatomy & histology*; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000502:physiology*; D018709:Statistics, Nonparametric; D013702:Temporal Lobe / Q000033:anatomy & histology*; D044465:White People; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins