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Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans

Molecular Psychiatry volume 14, pages 968–975 (2009)Cite this article

Abstract

In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder.

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Acknowledgements

This work was supported by the Intramural Research Program of the NIH, NIMH and NCI. We thank Dr Andrew Singleton for his technical advice resolving the microsatellites.

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Author notes

  1. B Kolachana and B Gold: These authors contributed equally to this work.

Authors and Affiliations

  1. Unit for Systems Neuroscience in Psychiatry, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA

    A Meyer-Lindenberg

  2. Neuroimaging Core Facility, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA

    A Meyer-Lindenberg & V Mattay

  3. Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA

    A Meyer-Lindenberg, B Kolachana, K K Nicodemus, V Mattay & D R Weinberger

  4. Central Institute of Mental Health, Mannheim, Germany

    A Meyer-Lindenberg

  5. Human Genetics Section, Laboratory of Genomic Diversity, Center for Cancer Research, NCI-Frederick, Frederick, MD, USA

    B Gold, A Olsh & M Dean

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  1. A Meyer-Lindenberg
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Correspondence to A Meyer-Lindenberg.

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Meyer-Lindenberg, A., Kolachana, B., Gold, B. et al. Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry 14, 968–975 (2009). https://doi.org/10.1038/mp.2008.54

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Keywords

  • vasopressin
  • AVPR1A
  • fMRI
  • neuroimaging
  • autism

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