This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (64)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Psychiatry, Other  • Genetics  • Genetic Disorders  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Emily M. Drabant, BA; Ahmad R. Hariri, PhD; Andreas Meyer-Lindenberg, MD, PhD; Karen E. Munoz, BA; Venkata S. Mattay, MD; Bhaskar S. Kolachana, PhD; Michael F. Egan, MD; Daniel R. Weinberger, MD

Arch Gen Psychiatry. 2006;63:1396-1406.

Context  Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val¹⁵⁸met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation.

Objectives  To examine COMT val¹⁵⁸met effects on corticolimbic circuitry reactivity and functional connectivity during processing of biologically salient stimuli, as well as the relationship to the temperamental trait of novelty seeking.

Design  Within-subject functional magnetic resonance imaging study.

Setting  National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md.

Patients  One hundred one healthy subjects of both sexes.

Results  We found that the met allele was associated with a dose-dependent increase in hippocampal formation and ventrolateral prefrontal cortex activation during viewing of faces displaying negative emotion. In met/met homozygotes, limbic and prefrontal regions showed increased functional coupling. Moreover, in these same subjects, the magnitude of amygdala-orbitofrontal coupling was inversely correlated with novelty seeking, an index of temperamental inflexibility.

Conclusions  Our results indicate that heritable variation in dopamine neurotransmission associated with the met allele of the COMT polymorphism results in heightened reactivity and connectivity in corticolimbic circuits. This may reflect a genetic predisposition for inflexible processing of affective stimuli, a mechanism possibly accounting for aspects of arousal and behavioral control that contribute to emotional dysregulation previously reported in met/met individuals.

Author Affiliations: Genes, Cognition, and Psychosis Program, National Institute of Mental Health Intramural Research Program, National Institutes of Health, US Department of Health and Human Services, Bethesda, Md. Dr Hariri is now with the Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pa.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

No Evidence for Generalized Increased Postoperative Responsiveness to Pain: A Combined Behavioral and Serial Functional Magnetic Resonance Imaging Study
Kupers et al.
Anesth. Analg. 2009;109:600-606.
ABSTRACT | FULL TEXT  

Get Aroused and Be Stronger: Emotional Facilitation of Physical Effort in the Human Brain
Schmidt et al.
J. Neurosci. 2009;29:9450-9457.
ABSTRACT | FULL TEXT  

Neurobiology of Wisdom: A Literature Overview
Meeks and Jeste
Arch Gen Psychiatry 2009;66:355-365.
ABSTRACT | FULL TEXT  

Evidence That Altered Amygdala Activity in Schizophrenia Is Related to Clinical State and Not Genetic Risk
Rasetti et al.
Am. J. Psychiatry 2009;166:216-225.
ABSTRACT | FULL TEXT  

Variation in dopamine genes influences responsivity of the human reward system
Dreher et al.
Proc. Natl. Acad. Sci. USA 2009;106:617-622.
ABSTRACT | FULL TEXT  

Psychosocial Stress and Psychosis. A Review of the Neurobiological Mechanisms and the Evidence for Gene-Stress Interaction
van Winkel et al.
Schizophr Bull 2008;34:1095-1105.
ABSTRACT | FULL TEXT  

Genetic Dissection of the Role of Catechol-O-Methyltransferase in Cognition and Stress Reactivity in Mice
Papaleo et al.
J. Neurosci. 2008;28:8709-8723.
ABSTRACT | FULL TEXT  

Influence of RGS2 on Anxiety-Related Temperament, Personality, and Brain Function
Smoller et al.
Arch Gen Psychiatry 2008;65:298-308.
ABSTRACT | FULL TEXT  

A Replicated Molecular Genetic Basis for Subtyping Antisocial Behavior in Children With Attention-Deficit/Hyperactivity Disorder
Caspi et al.
Arch Gen Psychiatry 2008;65:203-210.
ABSTRACT | FULL TEXT