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

J. W. Buckholtz, J. H. Callicott, B. Kolachana, A. R. Hariri, T. E. Goldberg, M. Genderson, M. F. Egan, V. S. Mattay, D. R. Weinberger, A. Meyer-Lindenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)313-324
Number of pages12
JournalMolecular psychiatry
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Keywords

  • Amygdala
  • Antisocial
  • Cingulate
  • Effective connectivity
  • Emotion regulation
  • Functional connectivity
  • fMRI

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality'. Together they form a unique fingerprint.

  • Cite this

    Buckholtz, J. W., Callicott, J. H., Kolachana, B., Hariri, A. R., Goldberg, T. E., Genderson, M., Egan, M. F., Mattay, V. S., Weinberger, D. R., & 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