QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 26, 2005, 25(4):836-842; doi:10.1523/JNEUROSCI.1792-04.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (59) Citing Articles via Google Scholar Google Scholar Articles by Smolka, M. N. Articles by Heinz, A. Search for Related Content PubMed PubMed Citation Articles by Smolka, M. N. Articles by Heinz, A.

 Previous Article  |  Next Article 

Neurobiology of Disease
Catechol-O-Methyltransferase val¹⁵⁸met Genotype Affects Processing of Emotional Stimuli in the Amygdala and Prefrontal Cortex

Michael N. Smolka,¹ Gunter Schumann,¹ Jana Wrase,² Sabine M. Grüsser,³ Herta Flor,¹ Karl Mann,¹ Dieter F. Braus,⁴ David Goldman,⁶ Christian Büchel,⁵ and Andreas Heinz²

¹Central Institute of Mental Health, 68159 Mannheim, Germany, ²Department of Psychiatry and ³Medical Psychology of the Charité, Charité Campus Mitte, Charité-University Medicine Berlin, 10117 Berlin, Germany, ⁴NeuroImage Nord, Department of Psychiatry, and ⁵Department of Neurology, University of Hamburg, 20246 Hamburg, Germany, and ⁶National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892

Catechol-O-methyltransferase (COMT) degrades the catecholamine neurotransmitters dopamine, epinephrine, and norepinephrine. A functional polymorphism in the COMT gene (val¹⁵⁸met) accounts for a fourfold variation in enzyme activity. The low-activity met¹⁵⁸ allele has been associated with improved working memory but with higher risk for anxiety-related behaviors. Using functional magnetic resonance imaging, we assessed the effects of COMT genotype on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 35 healthy subjects. The analysis of genotype effects was restricted to brain areas with robust activation by the task. To determine genedose effects, the number of met¹⁵⁸ alleles (0, 1, or 2) was correlated with the blood oxygen level-dependent (BOLD) response elicited by pleasant or unpleasant stimuli compared with neutral stimuli. COMT genotype had no significant impact on brain activation by pleasant stimuli but was related to the neural response to unpleasant stimuli: reactivity to unpleasant stimuli was significantly positively correlated with the number of met¹⁵⁸ alleles in the limbic system (left hippocampus, right amygdala, right thalamus), connected prefrontal areas (bilateral ventrolateral prefrontal cortex, right dorsolateral prefrontal cortex), and the visuospatial attention system (bilateral fusiform gyrus, left inferior parietal lobule). Genotype explained up to 38% of interindividual variance in BOLD response elicited by unpleasant stimuli. We conclude that (1) genetic variations can account for a substantial part of interindividual variance in task-related brain activation and that (2) increased limbic and prefrontal activation elicited by unpleasant stimuli in subjects with more met¹⁵⁸ alleles might contribute to the observed lower emotional resilience against negative mood states.

Key words: gene; catecholamine; emotion; amygdala; prefrontal; fMRI; COMT

---

Received May 10, 2004; revised November 19, 2004; accepted November 29, 2004.

This article has been cited by other articles:

				M. J. Herrmann, H. Wurflein, T. Schreppel, S. Koehler, A. Muhlberger, A. Reif, T. Canli, M. Romanos, C. P. Jacob, K.-P. Lesch, et al. Catechol-O-methyltransferase Val158Met genotype affects neural correlates of aversive stimuli processing Cogn Affect Behav Neurosci, June 1, 2009; 9(2): 168 - 172. [Abstract] [PDF]

				R. Kvetnansky, E. L. Sabban, and M. Palkovits Catecholaminergic Systems in Stress: Structural and Molecular Genetic Approaches Physiol Rev, April 1, 2009; 89(2): 535 - 606. [Abstract] [Full Text] [PDF]

				R. Rasetti, V. S. Mattay, L. M. Wiedholz, B. S. Kolachana, A. R. Hariri, J. H. Callicott, A. Meyer-Lindenberg, and D. R. Weinberger Evidence That Altered Amygdala Activity in Schizophrenia Is Related to Clinical State and Not Genetic Risk Am J Psychiatry, February 1, 2009; 166(2): 216 - 225. [Abstract] [Full Text] [PDF]

				A. Bertolino, L. Fazio, A. Di Giorgio, G. Blasi, R. Romano, P. Taurisano, G. Caforio, L. Sinibaldi, G. Ursini, T. Popolizio, et al. Genetically Determined Interaction between the Dopamine Transporter and the D2 Receptor on Prefronto-Striatal Activity and Volume in Humans J. Neurosci., January 28, 2009; 29(4): 1224 - 1234. [Abstract] [Full Text] [PDF]

				J.-C. Dreher, P. Kohn, B. Kolachana, D. R. Weinberger, and K. F. Berman Variation in dopamine genes influences responsivity of the human reward system PNAS, January 13, 2009; 106(2): 617 - 622. [Abstract] [Full Text] [PDF]

				T. Furmark, L. Appel, S. Henningsson, F. Ahs, V. Faria, C. Linnman, A. Pissiota, O. Frans, M. Bani, P. Bettica, et al. A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety J. Neurosci., December 3, 2008; 28(49): 13066 - 13074. [Abstract] [Full Text] [PDF]

				R. van Winkel, N. C. Stefanis, and I. Myin-Germeys Psychosocial Stress and Psychosis. A Review of the Neurobiological Mechanisms and the Evidence for Gene-Stress Interaction Schizophr Bull, November 1, 2008; 34(6): 1095 - 1105. [Abstract] [Full Text] [PDF]

				C. C.Y Wong and G. Schumann Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders Phil Trans R Soc B, October 12, 2008; 363(1507): 3213 - 3222. [Abstract] [Full Text] [PDF]

				S. J. Bishop, J. Fossella, C. J. Croucher, and J. Duncan COMT val158met Genotype Affects Recruitment of Neural Mechanisms Supporting Fluid Intelligence Cereb Cortex, September 1, 2008; 18(9): 2132 - 2140. [Abstract] [Full Text] [PDF]

				Y. Goto and A. A. Grace Dopamine Modulation of Hippocampal-Prefrontal Cortical Interaction Drives Memory-Guided Behavior Cereb Cortex, June 1, 2008; 18(6): 1407 - 1414. [Abstract] [Full Text] [PDF]

				A. Caspi, K. Langley, B. Milne, T. E. Moffitt, M. O'Donovan, M. J. Owen, M. Polo Tomas, R. Poulton, M. Rutter, A. Taylor, et al. A Replicated Molecular Genetic Basis for Subtyping Antisocial Behavior in Children With Attention-Deficit/Hyperactivity Disorder Arch Gen Psychiatry, February 1, 2008; 65(2): 203 - 210. [Abstract] [Full Text] [PDF]

				L. M. Williams and E. Gordon Dynamic Organization of the Emotional Brain: Responsivity, Stability, and Instability Neuroscientist, August 1, 2007; 13(4): 349 - 370. [Abstract] [PDF]

				J. Yacubian, T. Sommer, K. Schroeder, J. Glascher, R. Kalisch, B. Leuenberger, D. F. Braus, and C. Buchel Gene gene interaction associated with neural reward sensitivity PNAS, May 8, 2007; 104(19): 8125 - 8130. [Abstract] [Full Text] [PDF]

				E. M. Drabant, A. R. Hariri, A. Meyer-Lindenberg, K. E. Munoz, V. S. Mattay, B. S. Kolachana, M. F. Egan, and D. R. Weinberger Catechol O-methyltransferase Val158Met Genotype and Neural Mechanisms Related to Affective Arousal and Regulation Arch Gen Psychiatry, December 1, 2006; 63(12): 1396 - 1406. [Abstract] [Full Text] [PDF]

				E. Congdon and T. Canli The endophenotype of impulsivity: reaching consilience through behavioral, genetic, and neuroimaging approaches. Behav Cogn Neurosci Rev, December 1, 2005; 4(4): 262 - 281. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help