1. ¹Neuroimaging Core Facility, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA
2. ²Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA
3. ³Unit for Systems Neuroscience in Psychiatry, National Institute for Mental Health, NIH, DHHS, Bethesda, MD, USA

Correspondence: Dr A Meyer-Lindenberg, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, NIH, DHHS, 10-3C103, 9000 Rockville Pike, Bethesda, MD 20892-1365, USA. E-mail andreasml@nih.gov

⁴Current address: Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, E-729, Pittsburgh, PA 15213, USA.

⁵Current address: Division of Psychiatry Research, The Zucker Hillside Hospital, 75-59 263rd Street, Glen Oaks, NY 11004, USA.

⁶Current address: Merck & Co Inc., BL2-6, PO Box 4, West Point, PA 19486, USA.

Received 31 October 2006; Revised 23 February 2007; Accepted 3 April 2007; Published online 22 May 2007.

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.