Title: Affect-modulated startle reflex and dopamine D4 receptor gene variation
Abstract: PsychophysiologyVolume 47, Issue 1 p. 25-33 Affect-modulated startle reflex and dopamine D4 receptor gene variation Paul Pauli, Paul Pauli Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorAnnette Conzelmann, Annette Conzelmann Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorRonald F. Mucha, Ronald F. Mucha Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorPeter Weyers, Peter Weyers Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorChristina G. Baehne, Christina G. Baehne University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorAndreas J. Fallgatter, Andreas J. Fallgatter University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorChristian P. Jacob, Christian P. Jacob University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorKlaus Peter Lesch, Klaus Peter Lesch University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this author Paul Pauli, Paul Pauli Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorAnnette Conzelmann, Annette Conzelmann Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorRonald F. Mucha, Ronald F. Mucha Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorPeter Weyers, Peter Weyers Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorChristina G. Baehne, Christina G. Baehne University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorAndreas J. Fallgatter, Andreas J. Fallgatter University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorChristian P. Jacob, Christian P. Jacob University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this authorKlaus Peter Lesch, Klaus Peter Lesch University Hospital of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, GermanySearch for more papers by this author First published: 17 December 2009 https://doi.org/10.1111/j.1469-8986.2009.00923.xCitations: 22 Address reprint requests to: Prof. Dr. Paul Pauli, University of Würzburg, Department of Psychology, Biological Psychology, Clinical Psychology, and Psychotherapy, Marcusstr. 9-11, 97070 Würzburg, Germany. E-mail: [email protected] P. Pauli and A. Conzelmann contributed equally. Research was supported by the "Deutsche Forschungsgemeinschaft" (KFO 125/1, TP 7). We gratefully thank A. Boreatti, M. Heine, and J. Romanos for their help in the diagnostical screening of participants and R. Gerhard for her help in data preprocessing. The authors also thank N. Steigerwald and N. Döring for excellent technical assistance in DNA sample processing and genotyping. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The affect-modulated acoustic startle response (ASR) might be a promising indicator for emotional reactivity as an endophenotype (an intermediate level between genetics and phenotypes), which we expected to be associated with the DRD4 polymorphism. Therefore, the affect-modulated ASR was examined in 114 healthy volunteers, 74 lacking the DRD4 7R allele (7R-absent group) and 41 with at least one DRD4 7R allele (7R group). Results revealed the well-known affect–modulated ASR in the 7R-absent group. The 7R group, however, was characterized by a blunted affect-modulated ASR, especially by a reduced startle potentiation toward unpleasant pictures. Associations between the exploratory assessed 5-HTT, COMT, and DAT polymorphisms and affect-modulated ASR were not found. Results speak for the importance of the DRD4 polymorphism in modulating emotional responses and also for the usefulness of the affect-modulated ASR as an endophenotype. REFERENCES Amrhein, C., Mühlberger, A., Pauli, P., & Wiedemann, G. (2004). Modulation of event-related brain potentials during affective picture processing: A complement to startle reflex and skin conductance response? International Journal of Psychophysiology, 54, 231– 240. Anisman, H., Kelly, O., Hayley, S., Borowski, T., Merali, Z., & McIntyre, D. C. (2000). Acoustic startle and fear-potentiated startle in rats selectively bred for fast and slow kindling rates: Relation to monoamine activity. European Journal of Neuroscience, 12, 4405– 4416. Anokhin, A. P., Golosheykin, S., & Heath, A. C. (2007). Genetic and environmental influences on emotion-modulated startle reflex: A twin study. Psychophysiology, 4, 106– 112. Anokhin, A. P., Heath, A. C., Myers, E., Ralano, A., & Wood, S. (2003). Genetic influences on prepulse inhibition of startle reflex in humans. Neuroscience Letters, 353, 45– 48. Asghari, V., Sanyal, S., Buchwaldt, S., Paterson, A., Jovanovic, V., & Van Tol, H. H. (1995). Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. Journal of Neurochemistry, 65, 1157– 1165. Benjamin, J., Li, L., Patterson, C., Greenberg, B. D., Murphy, D. L., & Hamer, D. H. (1996). Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genetics, 12, 81– 84. Brocke, B., Armbruster, D., Müller, J., Hensch, T., Jacob, C. P., Lesch, K. P., et al. (2006). Serotonin transporter gene variation impacts innate fear processing: Acoustic startle response and emotional startle. Molecular Psychiatry, 11, 1106– 1112. Cabib, S., & Puglisi Allegra, S. (1996). Different effects of repeated stressful experiences on mesocortical and mesolimbic dopamine metabolism. Neuroscience, 73, 375– 380. Carlson, S. R., Katsanis, J., Iacono, W. G., & McGue, M. (1997). Emotional modulation of the startle reflex in twins: Preliminary findings. Biological Psychology, 46, 235– 246. Caseras, F. X., Fullana, M. A., Riba, J., Barbanoj, M. J., Aluja, A., & Torrubia, R. (2006). Influence of individual differences in the behavioral inhibition system and stimulus content (fear versus blood-disgust) on affective startle reflex modulation. Biological Psychology, 72, 251– 256. Castellanos, F. X., & Tannock, R. (2002). Neuroscience of attention-deficit/hyperactivity disorder: The search for endophenotypes. Nature Reviews. Neuroscience, 3, 617– 628. Chan, S. W., Goodwin, G. M., & Harmer, C. J. (2007). Highly neurotic never-depressed students have negative biases in information processing. Psychological Medicine, 37, 1281– 1291. Chang, F. M., Kidd, J. R., Livak, K. J., Pakstis, A. J., & Kidd, K. K. (1996). The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus. Human Genetics, 98, 91– 101. Conzelmann, A., Mucha, R. F., Jacob, C. P., Weyers, P., Romanos, J., Gerdes, A. B. M., et al. (2009). abnormal affective responsiveness in attention-deficit/hyperactivity disorder: Subtype differences. Biological Psychiatry, 65, 578– 585. Cook, E. W., Davis, T. L., Hawk, L. W., Spence, E. L., & Gautier, C. H. (1992). Fearfulness and startle potentiation during aversive visual stimuli. Psychophysiology, 29, 633– 645. Cook, E. W., Hawk, L. W., Davis, T. L., & Stevenson, V. E. (1991). Affective individual differences and startle reflex modulation. Journal of Abnormal Psychology, 100, 5– 13. Cuthbert, B. N., Bradley, M. M., & Lang, P. J. (1996). Probing picture perception: Activation and emotion. Psychophysiology, 33, 103– 111. Davidson, R. J., Pizzagalli, D., Nitschke, J. B., & Kalin, N. H. (2003). Parsing the subcomponents of emotion and disorders of emotion: Perspectives from affctive neuroscience. In R. J. Davidson, K. R. Scherer, & H. H. Goldsmith (Eds.), Handbook of affective sciences (pp. 8– 24). Oxford: Oxford University Press. Davidson, R. J., Scherer, K. R., & Goldsmith, H. H. (2003). Handbook of affective sciences. Oxford: Oxford University Press. De Luca, A., Rizzardi, M., Buccino, A., Alessandroni, R., Salvioli, G. P., Filograsso, N., et al. (2003). Association of dopamine D4 receptor (DRD4) exon III repeat polymorphism with temperament in 3-year-old infants. Neurogenetics, 4, 207– 212. Ebstein, R. P. (2006). The molecular genetic architecture of human personality: Beyond self-report questionnaires. Molecular Psychiatry, 11, 427– 445. Ebstein, R. P., Novick, O., Umansky, R., Priel, B., Osher, Y., Blaine, D., et al. (1996). Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nature Genetics, 12, 78– 80. Ehlis, A. C., Reif, A., Herrmann, M. J., Lesch, K. P., & Fallgatter, A. J. (2007). Impact of catechol-O-methyltransferase on prefrontal brain functioning in schizophrenia spectrum disorders. Neuropsychopharmacology, 32, 162– 170. First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1996). Structured clinical interview for DSM-IV Axis I disorders, clinician version (SCID-CV). Washington, DC: American Psychiatric Press. First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1997). Structured clinical interview for DSM-IV Personality Disorders (SCID-II). Washington, DC: American Psychiatric Press. Geier, A., Mucha, R. F., & Pauli, P. (2000). Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking. Psychopharmacology, 150, 283– 291. Geyer, M. A., & Braff, D. L. (1982). Habituation of the blink reflex in normals and schizophrenic patients. Psychophysiology, 19, 1– 6. Globisch, J., Hamm, A. O., Esteves, F., & Öhman, A. (1999). Fear appears fast: Temporal course of startle reflex potentiation in animal fearful subjects. Psychophysiology, 36, 66– 75. Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160, 636– 645. Grillon, C., & Baas, J. (2003). A review of the modulation of the startle reflex by affective states and its application in psychiatry. Clinical Neurophysiology, 114, 1557– 1579. Hamilton, S. P., Haghighi, F., Heiman, G. A., Klein, D. F., Hodge, S. E., Fyer, A. J., et al. (2000). Investigation of dopamine receptor (DRD4) and dopamine transporter (DAT) polymorphisms for genetic linkage or association to panic disorder. American Journal of Medical Genetics, 96, 324– 330. Hamm, A. O., Cuthbert, B. N., Globisch, J., & Vaitl, D. (1997). Fear and the startle reflex: Blink modulation and autonomic response patterns in animal and mutilation fearful subjects. Psychophysiology, 34, 97– 107. Hariri, A. R., Mattay, V. S., Tessitore, A., Fera, F., Smith, W. G., & Weinberger, D. R. (2002). Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacology, 27, 1036– 1040. Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al. (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science, 297, 400– 403. Jovanovic, V., Guan, H. C., & Van Tol, H. H. (1999). Comparative pharmacological and functional analysis of the human dopamine D4.2 and D4.10 receptor variants. Pharmacogenetics, 9, 561– 568. Koch, M. (1999). The neurobiology of startle. Progress in Neurobiology, 59, 107– 128. Kroner, S., Rosenkranz, J. A., Grace, A. A., & Barrionuevo, G. (2005). Dopamine modulates excitability of basolateral amygdala neurons in vitro. Journal of Neurophysiology, 93, 1598– 1610. Lakatos, K., Toth, I., Nemoda, Z., Ney, K., Sasvari-Szekely, M., & Gervai, J. (2000). Dopamine D4 receptor (DRD4) gene polymorphism is associated with attachment disorganization in infants. Molecular Psychiatry, 5, 633– 637. Lang, P. J. (1980). Behavioral treatment and bio-behavioral assessment: Computer applications. In J. B. Sidowski, J. H. Johnson, & T. A. Williams (Eds.), Technology in mental health care delivery systems (pp. 119– 137). Norwood, NJ: Ablex. Lang, P. J. (1995). The emotion probe. Studies of motivation and attention. American Psychologist, 50, 372– 385. Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1990). Emotion, attention, and the startle reflex. Psychological Review, 97, 377– 398. Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1999). International affective picture system (IAPS): Instruction manual and affective ratings. Technical Report A-4. Gainesville, FL: Center for Research in Psychophysiology, University of Florida. Larson, C. L., Ruffalo, D., Nietert, J. Y., & Davidson, R. J. (2000). Temporal stability of the emotion-modulated startle response. Psychophysiology, 37, 92– 101. Larson, C. L., Ruffalo, D., Nietert, J. Y., & Davidson, R. J. (2005). Stability of emotion-modulated startle during short and long picture presentation. Psychophysiology, 42, 604– 610. Laviolette, S. R., Lipski, W. J., & Grace, A. A. (2005). A subpopulation of neurons in the medial prefrontal cortex encodes emotional learning with burst and frequency codes through a dopamine D4 receptor-dependent basolateral amygdala input. Journal of Neuroscience, 25, 6066– 6075. LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155– 184. Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., et al. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527– 1531. Lichter, J. B., Barr, C. L., Kennedy, J. L., Van Tol, H. H., Kidd, K. K., & Livak, K. J. (1993). A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Human Molecular Genetics, 2, 767– 773. Lissek, S., & Powers, A. S. (2003). Sensation seeking and startle modulation by physically threatening images. Biological Psychology, 63, 179– 197. Loo, S. K., Specter, E., Smolen, A., Hopfer, C., Teale, P. D., & Reite, M. L. (2003). Functional effects of the DAT1 polymorphism on EEG measures in ADHD. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 986– 993. Lopez Leon, S., Croes, E. A., Sayed-Tabatabaei, F. A., Claes, S., Van Broeckhoven, C., & Van Duijn, C. M. (2005). The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: A meta-analysis. Biological Psychiatry, 57, 999– 1003. Manki, H., Kanba, S., Muramatsu, T., Higuchi, S., Suzuki, E., Matsushita, S., et al. (1996). Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders. Journal of Affective Disorders, 40, 7– 13. McCourt, W. F., Guerra, R. J., & Cutter, H. S. (1993). Sensation seeking and novelty seeking. Are they the same? Journal of Nervous & Mental Disease, 181, 309– 312. Meng, X.-L., Rosenthal, R., & Rubin, D. B. (1992). Comparing correlated correlation coefficients. Psychological Bulletin, 111, 172– 175. Meyer-Lindenberg, A., & Weinberger, D. R. (2006). Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nature Reviews. Neuroscience, 7, 818– 827. Miller, G. M., De La Garza, R. 2nd, Novak, M. A., & Madras, B. K. (2001). Single nucleotide polymorphisms distinguish multiple dopamine transporter alleles in primates: Implications for association with attention deficit hyperactivity disorder and other neuropsychiatric disorders. Molecular Psychiatry, 6, 50– 58. Missale, C., Nash, S. R., Robinson, S. W., Jaber, M., & Caron, M. G. (1998). Dopamine receptors: From structure to function. Physiological Reviews, 78, 189– 225. Montag, C., Buckholtz, J. W., Hartmann, P., Merz, M., Burk, C., Hennig, J., et al. (2008). COMT genetic variation affects fear processing: Psychophysiological evidence. Behavioral Neuroscience, 122, 901– 909. Mühlberger, A., Wiedemann, G., Herrmann, M. J., & Pauli, P. (2006). Phylo- and ontogenetic fears and the expectation of danger: Differences between spider- and flight-phobic subjects in cognitive and physiological responses to disorder-specific stimuli. Journal of Abnormal Psychology, 115, 580– 589. Mühlberger, A., Wieser, M. J., & Pauli, P. (2008). Darkness-enhanced startle responses in ecologically valid environments: A virtual tunnel driving experiment. Biological Psychology, 77, 47– 52. Munafo, M. R., Yalcin, B., Willis-Owen, S. A., & Flint, J. (2008). Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: Meta-analysis and new data. Biological Psychiatry, 63, 197– 206. Noble, E. P., Ozkaragoz, T. Z., Ritchie, T. L., Zhang, X., Belin, T. R., & Sparkes, R. S. (1998). D2 and D4 dopamine receptor polymorphisms and personality. American Journal of Medical Genetics, 81, 257– 267. Oak, J. N., Oldenhof, J., & Van Tol, H. H. (2000). The dopamine D(4) receptor: One decade of research. European Journal of Pharmacology, 405, 303– 327. Oniszczenko, W., & Dragan, W. L. (2005). Association between dopamine D4 receptor exon III polymorphism and emotional reactivity as a temperamental trait. Twin Research and Human Genetics, 8, 633– 637. Patrick, C. J., Bradley, M. M., & Lang, P. J. (1993). Emotion in the criminal psychopath: Startle reflex modulation. Journal of Abnormal Psychology, 102, 82– 92. Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48, 175– 187. Pissiota, A., Frans, O., Michelgard, A., Appel, L., Langstrom, B., Flaten, M. A., et al. (2003). Amygdala and anterior cingulate cortex activation during affective startle modulation: A PET study of fear. European Journal of Neuroscience, 18, 1325– 1331. Quirk, G. J., & Beer, J. S. (2006). Prefrontal involvement in the regulation of emotion: Convergence of rat and human studies. Current Opinion in Neurobiology, 16, 723– 727. Sabatinelli, D., Flaisch, T., Bradley, M. M., Fitzsimmons, J. R., & Lang, P. J. (2004). Affective picture perception: Gender differences in visual cortex? NeuroReport, 15, 1109– 1112. Savitz, J. B., & Ramesar, R. S. (2004). Genetic variants implicated in personality: A review of the more promising candidates. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics), 131, 20– 32. Schultz, W. (1994). Behavior-related activity of primate dopamine neurons. Revue Neurologique, 150, 634– 639. Serretti, A., Cristina, S., Lilli, R., Cusin, C., Lattuada, E., Lorenzi, C., et al. (2002). Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders. American Journal of Medical Genetics, 114, 361– 369. Shah, A. A., Sjovold, T., & Treit, D. (2004). Selective antagonism of medial prefrontal cortex D4 receptors decreases fear-related behaviour in rats. European Journal of Neuroscience, 19, 3393– 3397. Shin, L. M., Wright, C. I., Cannistraro, P. A., Wedig, M. M., McMullin, K., & Martis, B. (2005). A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry, 62, 273– 281. Smolka, M. N., Schumann, G., Wrase, J., Grüsser, S. M., Flor, H., Mann, K., et al. (2005). Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. Journal of Neuroscience, 25, 836– 842. Sommer, S. S., Lind, T. J., Heston, L. L., & Sobell, J. L. (1993). Dopamine D4 receptor variants in unrelated schizophrenic cases and controls. American Journal of Medical Genetics, 48, 90– 93. Tochigi, M., Hibino, H., Otowa, T., Kato, C., Marui, T., Ohtani, T., et al. (2006). Association between dopamine D4 receptor (DRD4) exon III polymorphism and neuroticism in the Japanese population. Neuroscience Letters, 398, 333– 336. Van Gestel, S., & Van Broeckhoven, C. (2003). Genetics of personality: Are we making progress? Molecular Psychiatry, 8, 840– 852. Citing Literature Volume47, Issue1January 2010Pages 25-33 ReferencesRelatedInformation
Publication Year: 2009
Publication Date: 2009-10-08
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 23
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