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Neural networks underlying trait aggression depend on MAOA gene alleles

Abstract

Low expressing alleles of the MAOA gene (MAOA-L) have been associated with an increased risk for developing an aggressive personality. This suggests an MAOA-L-specific neurobiological vulnerability associated with trait aggression. The neural networks underlying this vulnerability are unknown. The present study investigated genotype-specific associations between resting state brain networks and trait aggression (Buss-Perry Aggression Questionnaire) in 82 healthy Caucasian males. Genotype influences on aggression-related networks were studied for intrinsic and seed-based brain connectivity. Intrinsic connectivity was higher in the ventromedial prefrontal cortex (VMPFC) of MAOA-L compared to high expressing allele (MAOA-H) carriers. Seed-based connectivity analyses revealed genotype differences in the functional involvement of this region. MAOA genotype modulated the relationship between trait aggression and VMPFC connectivity with supramarginal gyrus (SMG) and areas of the default mode network (DMN). Separate analyses for the two groups were performed to better understand how the genotype modulated the relationship between aggression and brain networks. They revealed a positive correlation between VMPFC connectivity and aggression in right angular gyrus (AG) and a negative correlation in right SMG in the MAOA-L group. No such effect emerged in the MAOA-H carriers. The results indicate a particular relevance of VMPFC for aggression in MAOA-L carriers; in specific, a detachment from the DMN along with a strengthened coupling to the AG seems to go along with lower trait aggression. MAOA-L carriers may thus depend on a synchronization of emotion regulation systems (VMPFC) with core areas of empathy (SMG) to prevent aggression.

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Acknowledgements

This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG), IRTG 1328, IRTG 2150, and MA 2631/6-1), the Federal Ministry of Education and Research (APIC: 01EE1405A, APIC: 01EE1405B, and APIC: 01EE1405C), and the Interdisciplinary Center for Clinical Research (ICCR) Aachen (N4-2).

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Correspondence to Martin Klasen.

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Conflict of interest

FDZ was the recipient of an unrestricted award donated by the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE), and AstraZeneca (Young Minds in Psychiatry Award). He has also received research support from the German Federal Ministry for Economics and Technology, the European Union (EU), the German Society for Social Paediatrics and Adolescent Medicine, the Paul and Ursula Klein Foundation, the Dr. August Scheidel Foundation, the Princess Margaret Hospital Foundation (now the Perth Children’s Hospital Foundation), the Telethon Perth Children’s Hospital Research Fund (TPCHRF), the IZKF fund of the University Hospital of RWTH Aachen University, and a travel stipend donated by the GlaxoSmithKline Foundation. He is the recipient of an unrestricted educational grant, travel support, and speaker honoraria by Shire Pharmaceuticals, Germany. In addition, he has received support from the Raine Foundation for Medical Research (Raine Visiting Professorship) and editorial fees from Co-Action Publishing (Sweden). The authors report no further conflict of interest.

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Klasen, M., Wolf, D., Eisner, P.D. et al. Neural networks underlying trait aggression depend on MAOA gene alleles. Brain Struct Funct 223, 873–881 (2018). https://doi.org/10.1007/s00429-017-1528-6

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Keywords

  • Aggression
  • MAOA
  • Functional connectivity
  • Amygdala
  • Ventromedial prefrontal cortex
  • Angular gyrus