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Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality.

Publication ,  Journal Article
Buckholtz, JW; Callicott, JH; Kolachana, B; Hariri, AR; Goldberg, TE; Genderson, M; Egan, MF; Mattay, VS; Weinberger, DR; Meyer-Lindenberg, A
Published in: Molecular psychiatry
March 2008

Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC-amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior.

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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

March 2008

Volume

13

Issue

3

Start / End Page

313 / 324

Related Subject Headings

  • Psychiatry
  • Prefrontal Cortex
  • Photic Stimulation
  • Personality
  • Oxygen
  • Neuropsychological Tests
  • Neural Pathways
  • Monoamine Oxidase
  • Models, Biological
  • Male
 

Citation

APA
Chicago
ICMJE
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Buckholtz, J. W., Callicott, J. H., Kolachana, B., Hariri, A. R., Goldberg, T. E., Genderson, M., … Meyer-Lindenberg, A. (2008). Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular Psychiatry, 13(3), 313–324. https://doi.org/10.1038/sj.mp.4002020
Buckholtz, J. W., J. H. Callicott, B. Kolachana, A. R. Hariri, T. E. Goldberg, M. Genderson, M. F. Egan, V. S. Mattay, D. R. Weinberger, and A. Meyer-Lindenberg. “Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality.Molecular Psychiatry 13, no. 3 (March 2008): 313–24. https://doi.org/10.1038/sj.mp.4002020.
Buckholtz JW, Callicott JH, Kolachana B, Hariri AR, Goldberg TE, Genderson M, et al. Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular psychiatry. 2008 Mar;13(3):313–24.
Buckholtz, J. W., et al. “Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality.Molecular Psychiatry, vol. 13, no. 3, Mar. 2008, pp. 313–24. Epmc, doi:10.1038/sj.mp.4002020.
Buckholtz JW, Callicott JH, Kolachana B, Hariri AR, Goldberg TE, Genderson M, Egan MF, Mattay VS, Weinberger DR, Meyer-Lindenberg A. Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular psychiatry. 2008 Mar;13(3):313–324.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

March 2008

Volume

13

Issue

3

Start / End Page

313 / 324

Related Subject Headings

  • Psychiatry
  • Prefrontal Cortex
  • Photic Stimulation
  • Personality
  • Oxygen
  • Neuropsychological Tests
  • Neural Pathways
  • Monoamine Oxidase
  • Models, Biological
  • Male