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Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity

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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.

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Authors and Affiliations

  1. Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelsstrasse-30, 52074, Aachen, Germany

    Thomas Nickl-Jockschat, Valentin Markov, Frank Schneider & Ute Habel

  2. Juelich Aachen Research Alliance – Translational Brain Medicine, Juelich, Germany

    Thomas Nickl-Jockschat, Tony Stöcker, Ruiwang Huang, Frank Schneider, Ute Habel & N. Jon Shah

  3. Institute of Neurosciences and Medicine-4, Juelich Research Centre, Juelich, Germany

    Tony Stöcker, Ivan I. Maximov, Ruiwang Huang & N. Jon Shah

  4. Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany

    Axel Krug & Tilo Kircher

  5. Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University, Düsseldorf, Germany

    Simon B. Eickhoff

  6. Department of Neuroscience und Medicine, INM-1, Juelich Research Centre, Juelich, Germany

    Simon B. Eickhoff

  7. Institute of Human Genetics, RWTH Aachen University, Aachen, Germany

    Klaus Zerres

  8. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany

    Markus M. Nöthen

  9. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany

    Marcella Rietschel & Jens Treutlein

  10. Department of Neurology, RWTH Aachen University, Aachen, Germany

    N. Jon Shah

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  1. Thomas Nickl-Jockschat
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  2. Tony Stöcker
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Correspondence to Thomas Nickl-Jockschat.

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Jens Treutlein and Tilo Kircher share senior position.

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Nickl-Jockschat, T., Stöcker, T., Krug, A. et al. Genetic variation in the G72 gene is associated with increased frontotemporal fiber tract integrity. Eur Arch Psychiatry Clin Neurosci 265, 291–301 (2015). https://doi.org/10.1007/s00406-014-0516-6

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