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: Thomas Nickl-Jockschat, Tony Stöcker, Axel Krug, Valentin Markov, Ivan I Maximov, Ruiwang Huang, Frank Schneider, Ute Habel, Simon B Eickhoff, Klaus Zerres, Markus M Nöthen, Marcella Rietschel, N Jon Shah, Jens Treutlein, Tilo Kircher
• Journal: European archives of psychiatry and clinical neuroscience (Eur Arch Psychiatry Clin Neurosci) Vol. 265 Issue 4 Pg. 291-301 (Jun 2015) ISSN: 1433-8491 [Electronic] Germany
• PMID: 25031104 (Publication Type: Journal Article)

Chemical References

• Carrier Proteins
• DAOA protein, human
• Intracellular Signaling Peptides and Proteins

Topics

• Adolescent
• Adult
• Carrier Proteins (genetics)
• Diffusion Tensor Imaging
• Female
• Frontal Lobe (anatomy & histology)
• Genotype
• Humans
• Image Processing, Computer-Assisted
• Intracellular Signaling Peptides and Proteins
• Male
• Middle Aged
• Nerve Fibers (physiology)
• Statistics, Nonparametric
• Temporal Lobe (anatomy & histology)
• White People
• Young Adult