Variation of Human Amygdala Response During Threatening Stimuli as a Function of 5′HTTLPR Genotype and Personality Style


      In the brain, processing of fearful stimuli engages the amygdala, and the variability of its activity is associated with genetic factors as well as with emotional salience. The objective of this study was to explore the relevance of personality style for variability of amygdala response.


      We studied two groups (n = 14 in each group) of healthy subjects categorized by contrasting cognitive styles with which they attribute salience to fearful stimuli: so-called phobic prone subjects who exaggerate potential environmental threat versus so-called eating disorders prone subjects who tend to be much less centered around fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T during performance of a perceptual task of threatening stimuli and they were also matched for the genotype of the 5’ variable number tandem repeat (VNTR) polymorphism in the serotonin transporter.


      The fMRI results indicated that phobic prone subjects selectively recruit the amygdala to a larger extent than eating disorders prone subjects. Activity in the amygdala was also independently predicted by personality style and genotype of the serotonin transporter. Moreover, brain activity during a working memory task did not differentiate the two groups.


      The results of the present study suggest that aspects of personality style are rooted in biological responses of the fear circuitry associated with processing of environmental information.

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        • Adolphs R.
        • Tranel D.
        • Damasio H.
        • Damasio A.R.
        Fear and the human amygdala.
        J Neurosci. 1995; 15: 5879-5891
        • Ainsworth M.D.S.
        • Blehar M.
        • Waters E.
        • Wall S.
        Patterns of Attachment. Erlbaum, Hillsdale, NJ1978
        • Amaral D.G.
        The primate amygdala and the neurobiology of social behavior.
        Biol Psychiatry. 2002; 51: 11-17
        • Arciero G.
        • Gaetano P.
        • Maselli P.
        • Gentili N.
        Identity, personality and emotional regulation.
        in: Freeman A. Mahoney M. Devito P. Martin D. Cognition and Psychotherapy. 2 nd ed. Springer Publishing Company, New York2004
        • Arciero G.
        • Guidano V.F.
        Experience, Explanation and the Quest for Coherence. American Psychological Association, Washington, DC2000
        • Baumann M.D.
        • Lavenex P.
        • Mason W.A.
        • Capitanio J.P.
        • Amaral D.G.
        The development of mother-infant interactions after neonatal amygdala lesions in rhesus monkeys.
        J Neurosci. 2004; 24: 711-721
        • Bechara A.
        • Tranel D.
        • Damasio H.
        • Adolphs R.
        • Rockland C.
        • Damasio A.R.
        Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans.
        Science. 1995; 269: 1115-1118
        • Bertolino A.
        • Caforio G.
        • Blasi G.
        • De Candia M.
        • Latorre V.
        • Petruzzella V.
        • et al.
        Interaction of COMT val108/158 met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.
        Am J Psychiatry. 2004; 161: 1798-1805
        • Bowlby J.
        Attachment and Loss. Loss: Sadness and Depression. vol 3. Basic Books, New York1973
        • Bowlby J.
        Attachment and Loss. Separation: Anxiety and Anger. vol 2. Basic Books, New York1973
        • Bowlby J.
        The Making and the Breaking of Affectional Bonds. Tavistok, London1979
        • Bowlby J.
        Attachment and Loss. vol 1. Basic Books, New York1982
        • Bowlby J.
        The role of the childhood experience in cognitive disturbance.
        in: Mahoney M.J. Freeman A. Cognition and Psychotherapy. Basic Books, New York1985: 181-189
        • Bowlby J.
        A Secure Base. Basic Books, New York1988
        • Breiter H.C.
        • Etcoff N.L.
        • Whalen P.J.
        • Kennedy W.A.
        • Rauch S.L.
        • Buckner R.L.
        • et al.
        Response and habituation of the human amygdala during visual processing of facial expression.
        Neuron. 1996; 17: 875-887
        • Bretherton I.
        A communication perspective on attachment relationships and internal working models.
        Monogr Soc Res Child Dev. 1995; 60: 2-3
        • Buchel C.
        • Morris J.
        • Dolan R.J.
        • Friston K.J.
        Brain systems mediating aversive conditioning.
        Neuron. 1998; 20: 947-957
        • Cahill L.
        • Haier R.J.
        • Fallon J.
        • Alkire M.T.
        • Tang C.
        • Keator D.
        • et al.
        Amygdala activity at encoding correlated with long-term, free recall of emotional information.
        Proc Natl Acad Sci U S A. 1996; 93: 8016-8021
        • Canli T.
        • Sivers H.
        • Whitfield S.L.
        • Gotlib I.H.
        • Gabrieli J.D.
        Amygdala response to happy faces as a function of extraversion.
        Science. 2002; 296: 2191
        • Canli T.
        • Zhao Z.
        • Brewer J.
        • Gabrieli J.D.
        • Cahill L.
        Event-related activation in the human amygdala associates with later memory for individual emotional experience.
        J Neurosci. 2000; 20: RC99
        • Canli T.
        • Zhao Z.
        • Desmond J.E.
        • Kang E.
        • Gross J.
        • Gabrieli J.D.
        An fMRI study of personality influences on brain reactivity to emotional stimuli.
        Behav Neurosci. 2001; 115: 33-42
        • Caprara G.V.
        • Barbaranelli C.
        • Borgogni L.
        Big Five Questionnaire (BFQ). OS, Florence, Italy1993
        • Carstensen L.L.
        • Charles S.T.
        • Isaacowitz D.
        • Kennedy Q.
        Emotion and life-span personality development.
        in: Davidson R.J. Scherer K.R. Goldsmith H.H. Handbook of Affective Sciences. Oxford University Press, New York2003: 726-744
        • Caspi A.
        • Sugden K.
        • Moffitt T.
        • Taylor A.
        • Craig I.W.
        • Harrington H.
        • et al.
        Influence of life stress on depression.
        Science. 2003; 301: 386-389
        • Cloninger C.R.
        • Przybeck T.R.
        • Svrakic D.M.
        • Wetzel R.D.
        Temperament and Character Inventory (TCI). Center for Psychobiology of Personality, Washington University, St. Louis1994
        • Costa P.T.
        • McRae R.R.
        Personality Inventory (Short Form): Neuroticism, Extraversion and Openness (NEO: Revised NEO Personality Inventory [NEO-PI-R] and the NEO Five-Factor Inventory [NEO-FFI]): Professional Manual. Psychological Assessment Resources, Inc, Odessa, FL1992
        • Critchley H.D.
        • Mathias C.J.
        • Dolan R.J.
        Fear conditioning in humans.
        Neuron. 2002; 33: 653-663
        • Ekman P.
        Emotions Revealed. Henry Holt & Company, Incorporated, New York2003
        • Ekman P.
        • Friesen W.V.
        Pictures of Facial Affect. Consulting Psychologists Press, Palo Alto, CA1976
        • Everitt B.J.
        • Robbins T.W.
        The Amygdala. Wiley-Liss, New York1992
        • Eysenck H.J.
        • Eysenck S.B.G.
        Eysenck Personality Inventory (EPI). C. A. Educational and Industrial Testing Service, San Diego1968
        • Francis D.
        • Diorio J.
        • Liu D.
        • Meaney M.J.
        Nongenomic transmission across generations of maternal behavior and stress responses in the rat.
        Science. 1999; 286: 1155-1158
        • Francis D.D.
        • Szegda K.
        • Campbell G.
        • Martin W.D.
        • Insel T.R.
        Epigenetic sources of behavioral differences in mice.
        Nat Neurosci. 2003; 6: 445-446
        • Furmark T.
        • Tillfors M.
        • Garpenstrand H.
        • Marteinsdottir I.
        • Langstrom B.
        • Oreland L.
        • et al.
        Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia.
        Neurosci Lett. 2004; 362: 189-192
        • Goldsmith H.
        • Davidson R.
        in: Davidson R.J. Scherer K.R. Goldsmith H.H. Handbook of Affective Sciences. Oxford University Press, New York2003: 677-725
        • Grossman K.E.
        • Grossman E.
        The wider concept of attachment in cross-cultural research.
        Hum Dev. 1990; 33: 31-47
        • Guidano V.
        The Self in Process. The Guilford Press, New York1991
        • Hariri A.
        • Drabant E.
        • Munoz K.
        • Kolachana B.
        • Mattay V.
        • Egan M.
        • et al.
        A susceptibility gene for affective disorders and the response of the human amygdala.
        Arch Gen Psychiatry. 2005; 62: 146-152
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Kolachana B.
        • Fera F.
        • Goldman D.
        • et al.
        Serotonin transporter genetic variation and the response of the human amygdala.
        Science. 2002; 297: 400-403
        • Hariri A.R.
        • Mattay V.S.
        • Tessitore A.
        • Fera F.
        • Weinberger D.R.
        Neocortical modulation of the amygdala response to fearful stimuli.
        Biol Psychiatry. 2003; 53: 494-501
        • Heils A.
        • Mossner R.
        • Lesch K.P.
        The human serotonin transporter gene polymorphism-basic research and clinical implications.
        J Neural Transm. 1997; 104: 1005-1014
        • Hollingshead A.B.
        • Redlich F.C.
        Social Class and Mental Illness. Wiley, New York1958
        • Joseph R.
        Environmental influences on neural plasticity, the limbic system, emotional development and attachment.
        Child Psychiatry Hum Dev. 1999; 29: 189-208
        • LaBar K.S.
        • Gatenby J.C.
        • Gore J.C.
        • LeDoux J.E.
        • Phelps E.A.
        Human amygdala activation during conditioned fear acquisition and extinction.
        Neuron. 1998; 20: 937-945
        • LaBar K.S.
        • LeDoux J.E.
        • Spencer D.D.
        • Phelps E.A.
        Impaired fear conditioning following unilateral temporal lobectomy in humans.
        J Neurosci. 1995; 15: 6846-6855
        • LeDoux J.
        Fear and the brain.
        Biol Psychiatry. 1998; 44: 1229-1238
        • LeDoux J.E.
        The Emotional Brain. Touchstone, New York1996
        • Lesch K.P.
        • Bengel D.
        • Heils A.
        • Sabol S.Z.
        • Greenberg B.D.
        • Petri S.
        • et al.
        Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region.
        Science. 1996; 274: 1527-1531
        • Morris J.S.
        • Ohman A.
        • Dolan R.J.
        Conscious and unconscious emotional learning in the human amygdala.
        Nature. 1998; 393: 467-470
        • Muller J.
        • Corodimas K.P.
        • Fridel Z.
        • LeDoux J.E.
        Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli.
        Behav Neurosci. 1997; 111: 683-691
        • Oldfield R.C.
        The assessment and analysis of handedness.
        Neuropsychologia. 1971; 9: 97-113
        • Phan K.L.
        • Taylor S.F.
        • Welsh R.C.
        • Ho S.H.
        • Britton J.C.
        • Liberzon I.
        Neural correlates of individual ratings of emotional salience.
        Neuroimage. 2004; 21: 768-780
        • Picardi A.
        First steps in the assessment of cognitive-emotional organisation within the framework of Guidano’s model of the self.
        Psychother Psychosom. 2003; 72: 363-365
        • Posamentier M.T.
        • Abdi H.
        Processing faces and facial expressions.
        Neuropsychol Rev. 2003; 13: 113-143
        • Schwartz C.E.
        • Wright C.I.
        • Shin L.M.
        • Kagan J.
        • Rauch S.L.
        Inhibited and uninhibited infants “grown up”.
        Science. 2003; 300: 1952-1953
        • Watson D.
        • Clark L.A.
        • Carey G.
        Positive and negative affectivity and their relation to anxiety and depressive disorders.
        J Abnorm Psychol. 1988; 97: 346-353
        • Whalen P.J.
        • Rauch S.L.
        • Etcoff N.L.
        • McInerney S.C.
        • Lee M.B.
        • Jenike M.A.
        Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.
        J Neurosci. 1998; 18: 411-418
        • Young A.W.
        • Aggleton J.P.
        • Hellawell D.J.
        • Johnson M.
        • Broks P.
        • Hanley J.R.
        Face processing impairments after amygdalotomy.
        Brain. 1995; 118: 15-24
        • Zald D.H.
        • Pardo J.V.
        The neural correlates of aversive auditory stimulation.
        Neuroimage. 2002; 16: 746-753