10 - Neuro-imaging and genetics  pp. 317-344

Neuro-imaging and genetics

By Martin Reuter

Image View Previous Chapter Next Chapter

Jeffrey Gray's Reinforcement Sensitivity Theory (RST) (Gray 1970, 1982) is undoubtedly one of the most influential biological oriented personality theories available. Although the theory originated from animal research it could be extrapolated on humans and allows predictions on individual differences in behaviour. Moreover, RST can be applied to understand the mechanisms underlying the continuum between normal behaviour in healthy subjects and psychopathological syndromes like depression, anxiety, impulse control disorders and drug addiction.

In his initial 1982 theory Gray postulated that the three dimensions of his RST, the Behavioural Approach System (BAS), the Behavioural Inhibition System (BIS), and the Fight-Flight System (FFS) were mainly under the control of distinct neuroanatomical structures (Gray 1982). The BAS, which is activated by conditioned signals of reward or non-punishment, was assumed to be located in limbic brain structures and to be mainly under the control of the dopaminergic (DA) system. The neuroanatomical correlate of the BIS which is activated by conditioned signals of punishment should be the subiculum and septo-hippocampal structures. The FFS was hypothesized to be sensitive to unconditioned aversive stimuli (i.e., innately painful stimuli), mediating the emotions of rage and panic – this system was thought to be related to the state of negative affect (associated with pain). The neuroanatomical basis of the FFS systems are the basolateral and centromedial nuclei of the amygdala, the ventromedial nucleus of the hypothalamus, the central gray region of the midbrain, and the somatic and motor effector nuclei of the lower brain stem.

Abbar, M. , Courtet, P. , Bellivier, F. , Leboyer, M. , Boulenger, J. P. , Castelhau, D. , Ferreira, M. , Lambercy, C. , Mouthon, D. , Paoloni-Giacobino, A. , Vessaz, M. , Malafosse, A. and Buresi, C. (2001), Suicide attempts and the tryptophan hydroxylase gene, Molecular Psychiatry, 6, 268–73
Abdolmaleky, H. M. , Faraone, S. V. , Glatt, S. J. and Tsuang, M. T. (2004), Meta-analysis of association between the T102C polymorphism of the 5HT2a receptor gene and schizophrenia, Schizophrenia Research, 67, 53–62
Asberg, M. and Traskman, L. (1981), Studies of CSF 5-HIAA in depression and suicidal behaviour, Advances in Experimental Medicine and Biology, 133, 739–752
Benjamin, J., Ebstein, R. P. and Belmaker, R. H. (2002), Genes for human personality traits in J. Benjamin , R. P. Ebstein and R. H. Belmaker (eds), Molecular Genetics and the Human Personality (Washington DC: American Psychiatric Publishing), pp. 355–380
Bouchard, T. J. Jr (1994), Genes, environment, and personality, Science, 264, 1700–1701
Bouchard, T. J. Jr , Lykken, D. T. , McGue, M. , Segal, N. L. and Tellegen, A. (1990), Sources of human psychological differences: the Minnesota study of twins reared apart, Science, 250, 223–228
Brown, G. L. and Linnoila, M. I. (1990), CSF serotonin metabolite (5-HIAA) studies in depression, impulsivity, and violence, Journal of Clinical Psychiatry, 51 Suppl, 31–41
Canli, T. (2004), Functional brain mapping of extraversion and neuroticism: learning from individual differences in emotion processing, Journal of Personality, 72, 1105–1132
Canli, T. , Sivers, H. , Whitfield, S. L. , Gotlib, I. H. and Gabrieli, J. D. (2002), Amygdala response to happy faces as a function of extraversion, Science, 296, 2191
Canli, T. , Zhao, Z. , Desmond, J. E. , Kang, E. , Gross, J. and Gabrieli, J. D. E. (2001), An functional Magnetic Resonance Imaging study of personality influences on brain reactivity to emotional stimuli, Behavioral Neuroscience, 115, 33–42
Carver, C. S. and White, T. L. (1994), Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the Behavioural Inhibition System/Behavioural Approach System Scales, Journal of Personality and Social Psychology, 67, 319–333
Cloninger, C. R. (1987), A systematic method for clinical description and classification of personality variants: a proposal, Archives of General Psychiatry, 44, 573–588
Coccaro, E. F. , Kavoussi, R. J. , Sheline, Y. I. , Berman, M. E. and Csernansky, J. G. (1997), Impulsive aggression in personality disorder correlates with platelet 5-HT2A receptor binding, Neuropsychopharmacology, 16, 211–216
Corr, P. J. (2004), Reinforcement sensitivity theory and personality, Neuroscience and Biobehavioral Reviews, 28, 317–332
Costa, P. T. and McCrae, R. R. (1989), The NEO PI/FFI Manual Supplement (Odessa, FL: Psychological Assessment Resources)
Davis, K. L. , Panksepp, J. and Normansell, L. (2003), The affective neuroscience personality scales: normative data and implications, Neuro-Psychoanalysis, 5, 57–69
Depue, R. A. and Collins, P. F. (1999), Neurobiology of the structure of personality: dopamine, facilitation of incentive motivation, and extraversion, Behavioral and Brain Sciences, 22, 491–569
Depue, R. A. and Morrone-Strupinsky, J. V. (2005), A neurobehavioral model of affiliative bonding: implications for conceptualizing a human trait of affiliation, Behavioral and Brain Sciences, 28, 313–350
DiMaio, S. , Grizenko, N. and Joober, R. (2003), Dopamine genes and attention-deficit hyperactivity disorder: a review, Journal of Psychiatry and Neuroscience, 28, 27–38
Ebstein, R. P. , Segman, R. , Benjamin, J. , Osher, Y. , Nemanov, L. and Belmaker, R. H. (1997), 5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms, American Journal of Medical Genetics, 74, 65–72
Elovainio, M. , Puttonen, S. , Heponiemi, T. , Reuter, M. , Kivimaki, M. , Viikari, J. and Keltikangas-Järvinen, L. (2005), Relationship between DRD4 polymorphism and lipid metabolism: what is the role of novelty seeking?, Neuropsychobiology, 51, 53–58
Evans, J. , Reeves, B. , Platt, H. , Leibenau, A. , Goldman, D. , Jefferson, K. et al. (2000), Impulsiveness, serotonin genes and repetition of deliberate self-harm (DSH), Psychological Medicine, 30, 1327–1334
Eysenck, H. J. and Eysenck, M. W. (1985), Personal and Individual Differences: a Natural Science Approach (New York: Plenum Press)
Eysenck, H. J. and Eysenck, S. B. G. (1991), Manual of the Eysenck Personality Scales (London: Hodder & Stoughton)
Farde, L. , Gustavsson, J. P. and Jonsson, E. (1997), D2 dopamine receptors and personality traits, Nature, 385, 590
Gomez, R. , Cooper, A. and Gomez, A. (2000), Susceptibility to positive and negative mood states: test of Eysenck's, Gray's and Newman's theories, Personality and Individual Differences, 29, 351–365
Gray, J. A. (1970), The psychophysiological basis of introversion-extraversion, Behaviour Research and Therapy, 8, 249–266
Gray, J. A. (1982), The Neuropsychology of Anxiety: an Inquiry into the Functions of the Septo-hippocampal System (1st edn, Oxford: Oxford University Press)
Gray, J. A. and McNaughton, N. (2000), The Neuropsychology of Anxiety: an Inquiry into the Functions of the Septo-hippocampal System (2nd edn, Oxford: Oxford University Press)
Gray, J. R. and Braver, T. S. (2002), Personality predicts working-memory-related activation in the caudal anterior cingulate cortex, Cognitive, Affective and Behavioral Neuroscience, 2, 64–75
Greenberg, B. D. , Li, Q. , Lucas, F. R. , Hu, S. , Sirota, L. A. , Benjamin, J. , Lesch, K. P. , Hamer, D. and Murphy, D. L. (2000), Association between the serotonin transporter promoter polymorphism and personality traits in a primarily female population sample, American Journal of Medical Genetics, 96, 202–216
Gutknecht, G., Jacob, C., Strobel, A., Müller, J., Zeng, Y., Markert, C., Escher, A., Wendland, J., Reif, A., Mössner, R., Gross, C., Brocke, B. and Lesch, K. P. (2007), Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation, International Journal of Neuropsychopharmacology, 10, 309–320
Ham, B. J. , Kim, Y. H. , Choi, M. J. , Cha, J. H. , Choi, Y. K. and Lee, M. S. (2004), Serotonergic genes and personality traits in the Korean population, Neuroscience Letters, 354, 2–5
Hamer, D. (2002), Rethinking behavior genetics, Science, 298, 71–72
Hariri, A. R. , Bookheimer, S. Y. and Mazziotta, J. C. (2000), Modulating emotional responses: effects of a neocortical network on the limbic system, Neuroreport, 11, 43–48
Hariri, A. R. , Mattay, V. S. , Tessitore, A. , Fera, F. and Weinberger, D. R. (2003), Neocortical modulation of the amygdala response to fearful stimuli, Biological Psychiatry, 53, 494–501
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
Hariri, A. R. , Munoz, K. E. , Kolachana, B. , Goldsmith, D. R. , Mattay, V. S. and Goldber, T. (2003), Genetically driven variation in serotonergic neurotransmission alters amygdala reactivity associated with fearful temperament, Society for Neuroscience Abstracts, 662
Harvey, M. , Shink, E. , Tremblay, M. , Gagne, B. , Raymond, C. , Labbe, M. et al. (2004), Investigation of the tryptophan hydroxylase 2 (TPH2) gene in bipolar affective disorders, American Journal of Medical Genetics, Part B Neuropsychiatric Genetics, 130B, 151–152
Heisler, L. K. , Chu, H. M. , Brennan, T. J. , Danao, J. A. , Bajwa, P. , Parsons, L. H. and Tecott, L. H. (1998), Elevated anxiety and antidepressant-like responses in serotonin 5-HT1A receptor mutant mice, Proceedings of the National Academy of Sciences of the United States of America, 95, 15049–15054
Henderson, A. S. , Korten, A. E. , Jorm, A. F. , Jacomb, P. A. , Christensen, H. , Rodgers, B. et al. (2000), COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders, American Journal of Medical Genetics, 96, 102–107
Hennig, J. , Reuter, M. , Netter, P. , Burk, C. and Landt, O. (2005), Two types of aggression are differentially related to serotonergic acitvity and the A779C TPH polymorphism, Behavioral Neuroscience, 119, 16–25
Horn, N. R. , Dolan, M. , Elliott, R. , Deakin, J. F. W. and Woodruff, P. W. R. (2003), Response inhibition and impulsivity: an functional Magnetic Resonance Imaging study, Neuropsychologia, 41, 1959–1966
Jonsson, E. G. , Nothen, M. M. , Gustavsson, J. P. , Berggard, C. , Bunzel, R. , Forslund, K. et al. (2001), No association between serotonin 2A receptor gene variants and personality traits, Psychiatric Genetics, 11, 11–17
Kestler, L. P. , Malhotra, A. K. , Finch, C. , Adler, C. and Breier, A. (2000), The relation between dopamine D2 receptor density and personality: preliminary evidence from the NEO personality inventory-revised, Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 13, 48–52
Kuhn, K. U. , Meyer, K. , Nothen, M. M. , Gansicke, M. , Papassotiropoulos, A. and Maier, W. (1999), Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests, American Journal of Medical Genetics, 88, 168–172
Kusumi, I. , Suzuki, K. , Sasaki, Y. , Kameda, K. , Sasaki, T. and Koyama, T. (2002), Serotonin 5-HT(2A) receptor gene polymorphism, 5-HT(2A) receptor function and personality traits in healthy subjects: a negative study, Journal of Affective Disorders, 68, 235–241
Laakso, A. , Wallius, E. , Kajander, J. , Bergman, J. , Eskola, O. , Solin, O. , Ilonen, T. , Salokangas, R. K. R. , Syvalahti, E. and Hietala, J. (2003), Personality traits and striatal dopamine synthesis capacity in healthy subjects, American Journal of Psychiatry, 160, 904–910
Lachman, H. M. , Papolos, D. F. , Saito, T. , Yu, Y. M. , Szumlanski, C. L. and Weinshilboum, R. M. (1996), Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders, Pharmacogenetics, 6, 243–250
Lander, E. S. and Schork, N. J. (1994), Genetic dissection of complex traits, Science, 265, 2037–2048
Lang, P. J. , Bradley, M. M. and Cuthbert, B. (1995), International Affective Picture System (Gainsville, FL: Center for Research in Psychophysiology, University of Florida)
Lang, U. E. , Bajbouj, M. , Wernicke, C. , Rommelspacher, H. , Danker-Hopfe, H. and Gallinat, J. (2004), No association of a functional polymorphism in the serotonin transporter gene promoter and anxiety-related personality traits, Neuropsychobiology, 49, 182–184
Larsen, R. J. and Katelaar, T. (1991), Personality and susceptibility to positive and negative mood states, Journal of Personality and Social Psychology, 61, 132–140
Lerman, C. , Caporaso, N. E. , Bush, A. , Zheng, Y. L. , Audrain, J. , Main, D. , Shields, P. G. (2001), Tryptophan hydroxylase gene variant and smoking behavior, American Journal of Medical Genetics, B105, 518–520
Lesch, K. P. , Bengel, D. , Heils, A. , Sabol, S. Z. , Greenberg, B. D. , Petri, S. , Benjamin, J. , Muller, C. R. , Hamer, D. H. and Murphy, D. L. (1996), Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region, Science, 274, 1527–1531
Malleret, G. , Hen, R. , Guillou, J. L. , Segu, L. and Buhot, M. C. (1999), 5-HT1B receptor knock-out mice exhibit increased exploratory activity and enhanced spatial memory performance in the Morris water maze, Journal of Neuroscience, 19, 6157–6168
Mann, J. J. , Malone, K. M. , Nielsen, D. A. , Goldman, D. , Erdos, J. and Gelernter, J. (1997), Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients, American Journal of Psychiatry, 154, 1451–1453
Mattay, V. S. , Goldberg, T. E. , Fera, F. , Hariri, A. R. , Tessitore, A. , Egan, M. F. et al. (2003), Catechol O-methyltransferase val(158)-met genotype and individual variation in the brain response to amphetamine, Proceedings of the National Academy of Sciences of the United States of America, 100, 6186–6191
McNaughton, N. and Corr, P. J. (2004), A two-dimensional neuropsychology of defense: fear/anxiety and defensive distance, Neuroscience and Biobehavioral Review, 28, 285–305
Netter, P. , Reuter, M. and Hennig, J. (2005), Specificity of affiliation supported by neurotransmitter challenge tests and molecular genetics, Behavioral and Brain Sciences, 3, 359–360
New, A. S. , Gelernter, J. , Goodman, M. , Mitropoulou, V. , Koenigsberg, H. , Silverman, J. and Siever, L. J. (2001), Suicide, impulsive aggression, and HTR1B genotype, Biological Psychiatry, 50, 62–65
Nielsen, D. A. , Goldman, D. , Virkkunen, M. , Tokola, R. , Rawlings, R. and Linnoila, M. (1994), Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism, Archives of General Psychiatry, 51, 34–38
Noble, E. P. (2000), Addiction and its reward process through polymorphisms of the D-2 dopamine receptor gene: a review, European Psychiatry, 15, 79–89
Ochsner, K. N. , Bunge, S. A. , Gross, J. J. and Gabrieli, J. D. (2002), Rethinking feelings: an FMRI study of the cognitive regulation of emotion, Journal of Cognitive Neuroscience, 14, 1215–1229
Parsian, A. , Cloninger, C. R. , Sinha, R. and Zhang, Z. H. (2003), Functional variation in promoter region of monoamine oxidase A and subtypes of alcoholism: haplotype analysis, American Journal of Medical Genetics, Part B Neuropsychiatric Genetics, 117B, 46–50
Pohjalainen, T. , Rinne, J. O. , Nagren, K. , Lehikoinen, P. , Anttila, K. , Syvalahti, E. K. and Hietala, J. (1998), The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers, Molecular Psychiatry, 3, 256–260
Ramboz, S. , Saudou, F. , Amara, D. A. , Belzung, C. , Segu, L. , Misslin, R. et al. (1995), 5-HT1B receptor knock out, behavioral consequences, Behavioural Brain Research, 73, 305–312
Reif, A. and Lesch, K. P. (2003), Toward a molecular architecture of personality, Behavioral Brain Research, 139, 1–20
Reuter, M. , Peters, K. , Schroeter, K. , Koebke, W. , Lenardon, D. , Bloch, B. and Hennig, J. (2005), The influence of the dopaminergic system on cognitive functioning: a molecular genetic approach, Behavioural Brain Research, 164, 93–99
Reuter, M. , Schmitz, A. , Corr, P. and Hennig, J. (2006), Molecular genetics support for Gray's personality theory: the interaction of COMT and DRD2 polymorphisms predict Behavioural Inhibition System/Behavioural Approach System scales, International Journal of Neuropsychopharmacolgy, 9, 155–166
Reuter, M. , Stark, R. , Hennig, J. , Walter, B. , Kirsch, P. , Schienle, A. et al. (2004), Personality and emotion: test of Gray's personality theory by means of an functional Magnetic Resonance Imaging study, Behavioral Neuroscience, 118, 462–469
Reuter, M. and Hennig, J. (2005a), Pleiotropic effect of the TPH A779C polymorphism on nicotine dependence and personality, American Journal of Medical Genetics, Part B Neuropsychiatric Genetics, 134B, 20–24
Reuter, M. and Hennig, J. (2005b), Association of the functional COMT VAL158MET polymorphism with the personality trait of extraversion, NeuroReport, 16, 1135–1138
Reuter, M., Küpper, Y. and Hennig, J. (2007), Association between a polymorphism in the promoter region of the TPH2 gene and the personality trait of harm avoidance, International Journal of Neuropsychopharmacology, 10, 401–404
Rujescu, D. , Giegling, I. , Bondy, B. , Gietl, A. , Zill, P. and Moller, H. J. (2002), Association of anger-related traits with SNPs in the TPH gene, Molecular Psychiatry, 7, 1023–1029
Rujescu, D. , Giegling, I. , Gietl, A. , Hartmann, A. M. and Moller, H. J. (2003), A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits, Biological Psychiatry, 54, 34–39
Schmidt, L. A. , Fox, N. A. , Rubin, K. H. , Hu, S. and Hamer, D. H. (2002), Molecular genetics of shyness and aggression in preschoolers, Personality and Individual Differences, 33, 227–238
Schmidt, L. G. , Sander, T. , Kuhn, S. , Smolka, M. , Rommelspacher, H. , Samochowiec, J. et al. (2000), Different allele distribution of a regulatory MAOA gene promoter polymorphism in antisocial and anxious-depressive alcoholics, Journal of Neural Transmission, 107, 681–689
Souery, D. , Van Gestel, S. , Massat, I. , Blairy, S. , Adolfsson, R. , Blackwood, D. , Del-Favero, J. , Dikeos, D. , Jakovljevic, M. , Kaneva, R. , Lattuada, E. , Lerer, B. , Lilli, R. , Milanova, V. , Muir, W. , Nothen, M. , Oruc, L. , Papadimitriou, G. , Propping, P. , Schulze, T. , Serretti, A. , Shapira, B. , Smeraldi, E. , Stefanis, C. , Thomson, M. , Van Broeckhoven, C. and Mendlewicz, J. (2001), Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study, Biological Psychiatry, 49, 405–409
Soyka, M. , Preuss, U. W. , Koller, G. , Zill, P. and Bondy, B. (2004), Association of 5-HT1B receptor gene and antisocial behavior in alcoholism, Journal of Neural Transmission, 111, 101–109
Spanagel, R. and Weiss, F. (1999), The dopamine hypothesis of reward: past and current status, Trends in Neurosciences, 22, 521–527
Strobel, A. , Debener, S. , Anacker, K. , Muller, J. , Lesch, K. P. and Brocke, B. (2004), Dopamine D4 receptor exon III genotype influence on the auditory evoked novelty P3, Neuroreport, 15, 2411–2415
Strobel, A. , Gutknecht, L. , Rothe, C. , Reif, A. , Mossner, R. , Zeng, Y. , Brocke, B. and Lesch, K. P. (2003), Allelic variation in 5-HT1A receptor expression is associated with anxiety- and depression-related personality traits, Journal of Neural Transmission, 110, 1445–1453
Sullivan, P. F. , Jiang, Y. , Neale, M. C. , Kendler, K. S. and Straub, R. E. (2001), Association of the tryptophan hydroxylase gene with smoking initiation but not progression to nicotine dependence, American Journal of Medical Genetics, B105, 479–484
Teasdale, J. D. , Howard, R. J. , Cox, S. G. , Ha, Y. , Brammer, M. J. , Williams, S. C. R. and Checkley, S. A. (1999), Functional MRI study of the cognitive generation of affect, American Journal of Psychiatry, 156, 209–215
Thompson, J. , Thomas, N. , Singleton, A. , Piggot, M. , Lloyd, S. , Perry, E. K. , Morris, C. M. , Perry, R. H. , Ferrier, I. N. and Court, J. A. (1997), D2 dopamine receptor gene (DRD2) TaqI A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele, Pharmacogenetics, 7, 479–484
Tsai, S. J. , Hong, C. J. , Yu, Y. W. Y. and Chen, T. J. (2004), Association study of catechol-O-methyltransferase gene and dopamine D-4 receptor gene polymorphisms and personality traits in healthy young Chinese females, Neuropsychobiology, 50, 153–156
Vandenbergh, D. J. , Rodriguez, L. A. , Hivert, E. , Schiller, J. H. , Villareal, G. , Pugh, E. W. et al. (2000), Long forms of the dopamine receptor (DRD4) gene VNTR are more prevalent in substance abusers: no interaction with functional alleles of the catechol-o-methyltransferase (COMT) gene, American Journal of Medical Genetics, 96, 678–683
Wacker, J. , Reuter, M. , Hennig, J. and Stemmler, G. (2005), Sexually dimorphic link between dopamine D2 receptor gene and neuroticism-anxiety, NeuroReport, 16, 611–614
Walther, D. J. , Peter, J. U. , Bashammakh, S. , Hortnagl, H. , Voits, M. , Fink, H. et al. (2003), Synthesis of serotonin by a second tryptophan hydroxylase isoform, Science, 299, 76
Walther, D. J. and Bader, M. (2003), A unique central tryptophan hydroxylase isoform, Biochemical Pharmacology, 66, 1673–1680
Yasuno, F. , Suhara, T. , Sudo, Y. , Yamamoto, M. , Inoue, M. , Okubo, Y. and Suzuki, K. (2001), Relation among dopamine D-2 receptor binding, obesity and personality in normal human subjects, Neuroscience Letters, 300, 59–61
Zill, P. , Baghai, T. C. , Zwanzger, P. , Schule, C. , Eser, D. , Rupprecht, R. , Moller, H. J. , Bondy, B. and Ackenheil, M. (2004), SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression, Molecular Psychiatry, 9, 1030–1036
Zuckerman, M. (1993), P-impulsive sensation seeking and its behavioral, psychophysiological and biochemical correlates, Neuropsychobiology, 28, 30–36