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Developmental imaging genetics: Challenges and promises for translational research

Published online by Cambridge University Press:  09 August 2006

ESSI VIDING ,
DOUGLAS E. WILLIAMSON  and
AHMAD R. HARIRI
ESSI VIDING
Affiliation:
University College London
DOUGLAS E. WILLIAMSON
Affiliation:
University of Pittsburgh School of Medicine
AHMAD R. HARIRI
Affiliation:
University of Pittsburgh School of Medicine
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Abstract

Advances in molecular biology, neuroimaging, genetic epidemiology, and developmental psychopathology have provided a unique opportunity to explore the interplay of genes, brain, and behavior within a translational research framework. Herein, we begin by outlining an experimental strategy by which genetic effects on brain function can be explored using neuroimaging, namely, imaging genetics. We next describe some major findings in imaging genetics to highlight the effectiveness of this strategy for delineating biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. We then discuss the importance of applying imaging genetics to the study of psychopathology within a developmental framework. By beginning to move toward a systems-level approach to understanding pathways to behavioral outcomes as they are expressed across development, it is anticipated that we will move closer to understanding the complexities of the specific mechanisms involved in the etiology of psychiatric disease. Despite the numerous challenges that lie ahead, we believe that developmental imaging genetics has potential to yield highly informative results that will ultimately translate into public health benefits. We attempt to set out guidelines and provide exemplars that may help in designing fruitful translational research applications that incorporate a developmental imaging genetics strategy.This research was supported in part by funding from the United Kingdom National Programme on Forensic Mental Health Research and Development (to E.V.), the Medical Research Council Grant G0401170 (to E.V.), the National Institute of Mental Health Grants K01-MH001957 (to D.E.W.) and K01-MH072837 (to A.R.H.), as well as an NARSAD Young Investigator Award (to A.R.H.).

Type
Research Article
Information
Development and Psychopathology , Volume 18 , Issue 3 , September 2006 , pp. 877 - 892
Copyright
© 2006 Cambridge University Press

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References

REFERENCES

Ansorge, M. S., Zhou, M., Lira, A., Hen, R., & Gingrich, J. A. (2004). Early-life blockade of the 5HT transporter alters emotional behavior in adult mice. Science, 306, 879–881.Google Scholar
Azmitia, E. C., & Gannon, P. J. (1986). The primate serotonergic system: A review of human and animal studies and a report on macaca fascicularis. Advances in Neurology, 43, 407–468.Google Scholar
Bailey, S. (2002). Expert paper: Antisocial personality disorder: Children and adolescents. London: NHS National Programme on Forensic Mental Health Research and Development.
Beauregard, M., Levesque, J., & Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. Journal of Neuroscience, 21, RC165.Google Scholar
Bennett, A. J., Lesch, K. P., Heils, A., Long, J. C., Lorenz, J. G., Shoaf, S. E., et al. (2002). Early experience and serotonin transporter gene variation interact to influence primate CNS function. Molecular Psychiatry, 7, 118–122.Google Scholar
Bertolino, A., Arciero, G., Rubino, V., Latorre, V., De Candia, M., Mazzola, V., et al. (2005). Variation of human amygdala response during threatening stimuli as a function of 5′HTTLPR genotype and personality style. Biological Psychiatry, 57, 1517–1525.Google Scholar
Blier, P., & de Montigny, C. (1999). Serotonin and drug-induced therapeutic responses in major depression, obsessive–compulsive and panic disorders. Neuropsychopharmacology, 21(Suppl), 91S–98S.Google Scholar
Brown, S. M., Peet, E., Manuck, S. B., Williamson, D. E., Dahl, R. E., Ferrell, R. E., et al. (2005). A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Molecular Psychiatry, 10, 884–888.Google Scholar
Canli, T., Omura, K., Haas, B. W., Fallgatter, A., Constable, R. T., & Lesch, K. P. (2005). Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task. Proceedings of the National Academy of Sciences of the United States of America, 102, 12224–12229.Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386–389.Google Scholar
Champoux, M., Bennett, A., Shannon, C., Higley, J. D., Lesch, K. P., & Suomi, S. J. (2002). Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Molecular Psychiatry, 7, 1058–1063.Google Scholar
Cicchetti, D., & Cannon, T. D. (1999). Neurodevelopmental processes in the ontogenesis and epigenesis of psychopathology. Developmental Psychopathology, 11, 375–393.Google Scholar
Cloninger, C. R. (1986). A unified biosocial theory of personality and its role in the development of anxiety states. Psychiatric Developments, 4, 167–226.Google Scholar
Cloninger, C. R., Svrakic, D. M., & Przybeck, T. R. (1993). A psychobiological model of temperament and character. Archives in General Psychiatry, 50, 975–990.Google Scholar
Curtis, W. J., & Cicchetti, D. (2003). Moving research on resilience into the 21st century: Theoretical and methodological considerations in examining the biological contributors to resilience. Developmental Psychopathology, 15, 773–810.Google Scholar
Domschke, K., Braun, M., Ohrmann, P., Suslow, T., Kugel, H., Bauer, J., et al. (2005). Association of the functional—1019c/g 5-HT 1a polymorphism with prefrontal cortex and amygdala activation measured with 3 t fMRI in panic disorder. International Journal of Neuropsychopharmacology, 9, 349–355.Google Scholar
Du, L., Bakish, D., & Hrdina, P. D. (2000). Gender differences in association between serotonin transporter gene polymorphism and personality traits. Psychiatric Genetics, 10, 159–164.Google Scholar
Eggers, B., Hermann, W., Barthel, H., Sabri, O., Wagner, A., & Hesse, S. (2003). The degree of depression in hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson's disease. Journal of Neurology, 250, 576–580.Google Scholar
Eley, T. C., Lichtenstein, P., & Moffitt, T. E. (2003). A longitudinal behavioral genetic analysis of the etiology of aggressive and nonaggressive antisocial behavior. Developmental Psychopathology, 15, 383–402.Google Scholar
Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., et al. (2004). Gene–environment interaction analysis of serotonin system markers with adolescent depression. Molecular Psychiatry, 9, 908–915.Google Scholar
Esaki, T., Cook, M., Shimoji, K., Murphy, D. L., Sokoloff, L., & Holmes, A. (2005). Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice. Proceedings of the National Academy of Sciences of the United States of America, 102, 5582–5587.Google Scholar
Frick, P. J., Cornell, A. H., Barry, C. T., Bodin, S. D., & Dane, H. E. (2003). Callous-unemotional traits and conduct problems in the prediction of conduct problem severity, aggression, and self-report of delinquency. Journal of Abnormal Child Psychology, 31, 457–470.Google Scholar
Furmark, T., Tillfors, M., Garpenstrand, H., Marteinsdottir, I., Langstrom, B., Oreland, L., et al. (2004). Serotonin transporter polymorphism linked to amygdala excitability and symptom severity in patients with social phobia. Neuroscience Letters, 362, 1–4.Google Scholar
Garpenstrand, H., Annas, P., Ekblom, J., Oreland, L., & Fredrikson, M. (2001). Human fear conditioning is related to dopaminergic and serotonergic biological markers. Behavioral Neuroscience, 115, 358–364.Google Scholar
Gaspar, P. (2004). Genetic models to understand how serotonin acts during development. Journal de la Société de Biologie, 198, 18–21.Google Scholar
Gelernter, J., Kranzler, H., & Cubells, J. F. (1997). Serotonin transporter protein (slc6a4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects. Human Genetics, 101, 243–246.Google Scholar
Glatt, C. E., & Freimer, N. B. (2002). Association analysis of candidate genes for neuropsychiatric disease: The perpetual campaign. Trends in Genetics, 18, 307–312.Google Scholar
Hare, R. D., Hart, S. D., & Harpur, T. J. (1991). Psychopathy and the DSM-IV criteria for antisocial personality disorder. Journal of Abnormal Psychology, 100, 391–398.Google Scholar
Hariri, A. R., Bookheimer, S. Y., & Mazziotta, J. C. (2000). Modulating emotional responses: Effects of a neocortical network on the limbic system. Neuroreport, 11, 43–48.Google Scholar
Hariri, A. R., Drabant, E. M., Munoz, K. E., Kolachana, B. S., Mattay, V. S., Egan, M. F., et al. (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives in General Psychiatry, 62, 146–152.Google Scholar
Hariri, A. R., Drabant, E. M., & Weinberger, D. R. (2006). Imaging genetics: Perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biological Psychiatry, 59, 888–897.Google Scholar
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.Google Scholar
Hariri, A. R., Mattay, V. S., Tessitore, A., Fera, F., & Weinberger, D. R. (2003). Neocortical modulation of the amygdala response to fearful stimuli. Biological Psychiatry, 53, 494–501.Google Scholar
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.Google Scholar
Hariri, A. R., Tessitore, A., Mattay, V. S., Fera, F., & Weinberger, D. R. (2002). The amygdala response to emotional stimuli: A comparison of faces and scenes. Neuroimage, 17, 317–323.Google Scholar
Hariri, A. R., & Weinberger, D. R. (2003a). Functional neuroimaging of genetic variation in serotonergic neurotransmission. Genes, Brain and Behavior, 2, 314–349.Google Scholar
Hariri, A. R., & Weinberger, D. R. (2003b). Imaging genomics. British Medical Bulletin, 65, 259–270.Google Scholar
Heils, A., Teufel, A., Petri, S., Stober, G., Riederer, P., Bengel, D., et al. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66, 2621–2624.Google Scholar
Heinz, A., Braus, D. F., Smolka, M. N., Wrase, J., Puls, I., Hermann, D., et al. (2005). Amygdala–prefrontal coupling depends on a genetic variation of the serotonin transporter. Nature Neuroscience, 8, 20–21.Google Scholar
Heinz, A., Higley, J. D., Gorey, J. G., Saunders, R. C., Jones, D. W., Hommer, D., et al. (1998). In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates. American Journal of Psychiatry, 155, 1023–1028.Google Scholar
Heinz, A., Jones, D. W., Bissette, G., Hommer, D., Ragan, P., Knable, M., et al. (2002). Relationship between cortisol and serotonin metabolites and transporters in alcoholism. Pharmacopsychiatry, 35, 127–134.Google Scholar
Heinz, A., Jones, D. W., Mazzanti, C., Goldman, D., Ragan, P., Hommer, D., et al. (2000). A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biological Psychiatry, 47, 643–649.Google Scholar
Holmes, A., & Hariri, A. R. (2003). The serotonin transporter gene-linked polymorphism and negative emotionality: Placing single gene effects in the context of genetic background and environment. Genes, Brain and Behavior, 2, 332–335.Google Scholar
Holmes, A., Lit, Q., Murphy, D. L., Gold, E., & Crawley, J. N. (2003). Abnormal anxiety-related behavior in serotonin transporter null mutant mice: The influence of genetic background. Genes, Brain and Behavior, 2, 365–380.Google Scholar
Katsuragi, S., Kunugi, H., Sano, A., Tsutsumi, T., Isogawa, K., Nanko, S., et al. (1999). Association between serotonin transporter gene polymorphism and anxiety-related traits. Biological Psychiatry, 45, 368–370.Google Scholar
Kaufman, J., Yang, B. Z., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D., Krystal, J. H., et al. (2004). Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings of the National Academy of Sciences of the United States of America, 101, 17316–17321.Google Scholar
Keightley, M. L., Winocur, G., Graham, S. J., Mayberg, H. S., Hevenor, S. J., & Grady, C. L. (2003). An fMRI study investigating cognitive modulation of brain regions associated with emotional processing of visual stimuli. Neuropsychologia, 41, 585–596.Google Scholar
Kendler, K. S., Kuhn, J. W., Vittum, J., Prescott, C. A., & Riley, B. (2005). The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: A replication. Archives in General Psychiatry, 62, 529–535.Google Scholar
Kim-Cohen, J., Caspi, A., Moffitt, T. E., Harrington, H., Milne, B. J., & Poulton, R. (2003). Prior juvenile diagnoses in adults with mental disorder: Developmental follow-back of a prospective-longitudinal cohort. Archives in General Psychiatry, 60, 709–717.Google Scholar
Kreek, M. J., & Koob, G. F. (1998). Drug dependence: Stress and dysregulation of brain reward pathways. Drug and Alcohol Dependence, 51, 23–47.Google Scholar
LaForge, K. S., Yuferov, V., & Kreek, M. J. (2000). Opioid receptor and peptide gene polymorphisms: Potential implications for addictions. European Journal of Pharmacology, 410, 249–268.Google Scholar
Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., et al. (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860–921.Google Scholar
Lange, K., Williams, L. M., Young, A. W., Bullmore, E. T., Brammer, M. J., Williams, S. C., et al. (2003). Task instructions modulate neural responses to fearful facial expressions. Biological Psychiatry, 53, 226–232.Google Scholar
LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155–184.Google Scholar
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.Google Scholar
Lesch, K. P., & Mossner, R. (1998). Genetically driven variation in serotonin uptake: Is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? Biological Psychiatry, 44, 179–192.Google Scholar
Lewis, D. A. (1997). Development of the prefrontal cortex during adolescence: Insights into vulnerable neural circuits in schizophrenia. Neuropsychopharmacology, 16, 385–398.Google Scholar
Little, K. Y., McLaughlin, D. P., Zhang, L., Livermore, C. S., Dalack, G. W., McFinton, P. R., et al. (1998). Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and MRNA levels. American Journal of Psychiatry, 155, 207–213.Google Scholar
Lucki, I. (1998). The spectrum of behaviors influenced by serotonin. Biological Psychiatry, 44, 151–162.Google Scholar
Luthar, S. S., Cicchetti, D., & Becker, B. (2000). The construct of resilience: A critical evaluation and guidelines for future work. Child Development, 71, 543–562.Google Scholar
Malhotra, A. K., & Goldman, D. (1999). Benefits and pitfalls encountered in psychiatric genetic association studies. Biological Psychiatry, 45, 544–550.Google Scholar
Malison, R. T., Price, L. H., Berman, R., van Dyck, C. H., Pelton, G. H., Carpenter, L., et al. (1998). Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biological Psychiatry, 44, 1090–1098.Google Scholar
Mayberg, H. S. (2003a). Modulating dysfunctional limbic–cortical circuits in depression: Towards development of brain-based algorithms for diagnosis and optimised treatment. British Medical Bulletin, 65, 193–207.Google Scholar
Mayberg, H. S. (2003b). Positron emission tomography imaging in depression: A neural systems perspective. Neuroimaging Clinics of North America, 13, 805–815.Google Scholar
Mazzanti, C. M., Lappalainen, J., Long, J. C., Bengel, D., Naukkarinen, H., Eggert, M., et al. (1998). Role of the serotonin transporter promoter polymorphism in anxiety-related traits. Archives in General Psychiatry, 55, 936–940.Google Scholar
Meaney, M. J., & Szyf, M. (2005). Environmental programming of stress responses through DNA methylation: Life at the interface between a dynamic environment and a fixed genome. Dialogues in Clinical Neuroscience, 7, 103–123.Google Scholar
Melke, J., Landen, M., Baghei, F., Rosmond, R., Holm, G., Bjorntorp, P., et al. (2001). Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women. American Journal of Medical Genetics, 105, 458–463.Google Scholar
Meyer-Lindenberg, A., Hariri, A. R., Munoz, K. E., Mervis, C. B., Mattay, V. S., Morris, C. A., et al. (2005). Neural correlates of genetically abnormal social cognition in williams syndrome. Nature Neuroscience, 8, 991–993.Google Scholar
Moldin, S. O., & Gottesman, I. I.. (1997). At issue: Genes, experience, and chance in schizophrenia—Positioning for the 21st century. Schizophrenia Bulletin, 23, 547–561.Google Scholar
Moreno, F. A., Rowe, D. C., Kaiser, B., Chase, D., Michaels, T., Gelernter, J., et al. (2002). Association between a serotonin transporter promoter region polymorphism and mood response during tryptophan depletion. Molecular Psychiatry, 7, 213–216.Google Scholar
Munafo, M. R., Clark, T., & Flint, J. (2005). Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis. Molecular Psychiatry, 10, 415–419.Google Scholar
Murphy, D. L., Andrews, A. M., Wichems, C. H., Li, Q., Tohda, M., & Greenberg, B. (1998). Brain serotonin neurotransmission: An overview and update with an emphasis on serotonin subsystem heterogeneity, multiple receptors, interactions with other neurotransmitter systems, and consequent implications for understanding the actions of serotonergic drugs. Journal of Clinical Psychiatry, 59(Suppl. 15), 4–12.Google Scholar
Nakamura, K., Kawashima, R., Nagumo, S., Ito, K., Sugiura, M., Kato, T., et al. (1998). Neuroanatomical correlates of the assessment of facial attractiveness. Neuroreport, 9, 753–757.Google Scholar
Narumoto, J., Yamada, H., Iidaka, T., Sadato, N., Fukui, K., Itoh, H., et al. (2000). Brain regions involved in verbal or non-verbal aspects of facial emotion recognition. Neuroreport, 11, 2571–2576.Google Scholar
Neumeister, A., Konstantinidis, A., Stastny, J., Schwarz, M. J., Vitouch, O., Willeit, M., et al. (2002). Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression. Archives in General Psychiatry, 59, 613–620.Google Scholar
Patkar, A. A., Berrettini, W. H., Mannelli, P., Gopalakrishnan, R., Hoehe, M. R., Bilal, L., et al. (2004). Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers. Psychiatry and Genetics, 14, 25–32.Google Scholar
Pezawas, L., Meyer-Lindenberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., et al. (2005). 5HTTLPR polymorphism impacts human cingulate-amygdala interactions: A genetic susceptibility mechanism for depression. Nature Neuroscience, 8, 828–834.Google Scholar
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003a). Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biological Psychiatry, 54, 504–514.Google Scholar
Phillips, M. L., Drevets, W. C., Rauch, S. L., & Lane, R. (2003b). Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biological Psychiatry, 54, 515–528.Google Scholar
Plomin, R., Owen, M. J., & McGuffin, P. (1994). The genetic basis of complex human behaviors. Science, 264, 1733–1739.Google Scholar
Pohorecky, L. A. (1990). Interaction of ethanol and stress: Research with experimental animals—An update. Alcohol and Alcoholism, 25, 263–276.Google Scholar
Pohorecky, L. A. (1991). Stress and alcohol interaction: An update of human research. Alcoholism and Clinical Experimental Research, 15, 438–459.Google Scholar
Reif, A., & Lesch, K. P. (2003). Toward a molecular architecture of personality. Behavioural Brain Research, 139, 1–20.Google Scholar
Rosenkranz, J. A., Moore, H., & Grace, A. A. (2003). The prefrontal cortex regulates lateral amygdala neuronal plasticity and responses to previously conditioned stimuli. Journal of Neuroscience, 23, 11054–11064.Google Scholar
Rutter, M., Kim-Cohen, J., & Maughan, B. (2006). Continuities and discontinuities in psychopathology between childhood and adult life. Journal of Child Psychology and Psychiatry, 47, 276–295.Google Scholar
Rutter, M., Moffitt, T. E., & Caspi, A. (2006). Gene–environment interplay and psychopathology: Multiple varieties but real effects. Journal of Child Psychology and Psychiatry and Allied Disciplines, 47, 226–261.Google Scholar
Sadikot, A. F., & Parent, A. (1990). The monoaminergic innervation of the amygdala in the squirrel monkey: An immunohistochemical study. Neuroscience, 36, 431–447.Google Scholar
Schinka, J. A., Busch, R. M., & Robichaux-Keene, N. (2004). A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Molecular Psychiatry, 9, 197–202.Google Scholar
Schuckit, M. A. (1998). Biological, psychological and environmental predictors of the alcoholism risk: A longitudinal study. Journal of the Studies on Alcohol, 59, 485–494.Google Scholar
Schwartz, C. E., Wright, C. I., Shin, L. M., Kagan, J., & Rauch, S. L. (2003). Inhibited and uninhibited infants “grown up”: Adult amygdalar response to novelty. Science, 300, 1952–1953.Google Scholar
Scott, S., Knapp, M., Henderson, J., & Maughan, B. (2001). Financial cost of social exclusion: Follow up study of antisocial children into adulthood. British Medical Journal, 323(7306), 191–195.Google Scholar
Sen, S., Burmeister, M., & Ghosh, D. (2004). Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. American Journal of Medical Genetics, 127B, 85–89.Google Scholar
Shioe, K., Ichimiya, T., Suhara, T., Takano, A., Sudo, Y., Yasuno, F., et al. (2003). No association between genotype of the promoter region of serotonin transporter gene and serotonin transporter binding in human brain measured by pet. Synapse, 48, 184–188.Google Scholar
Siegle, G. J., Steinhauer, S. R., Thase, M. E., Stenger, V. A., & Carter, C. S. (2002). Can't shake that feeling: Event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry, 51, 693–707.Google Scholar
Smith, H. R., Daunais, J. B., Nader, M. A., & Porrino, L. J. (1999). Distribution of [3H]citalopram binding sites in the nonhuman primate brain. Annals of the New York Academy of Science, 877, 700–702.Google Scholar
Tessitore, A., Hariri, A. R., Fera, F., Smith, W. G., Chase, T. N., Hyde, T. M., et al. (2002). Dopamine modulates the response of the human amygdala: A study in Parkinson's disease. Journal of Neuroscience, 22, 9099–9103.Google Scholar
van Dyck, C. H., Malison, R. T., Staley, J. K., Jacobsen, L. K., Seibyl, J. P., Laruelle, M., et al. (2004). Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype. American Journal of Psychiatry, 161, 525–531.Google Scholar
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., et al. (2001). The sequence of the human genome. Science, 291, 1304–1351.Google Scholar
Viding, E., Blair, R. J., Moffitt, T. E., & Plomin, R. (2005). Evidence for substantial genetic risk for psychopathy in 7-year-olds. Journal of Child Psychology and Psychiatry and Allied Disciplines, 46, 592–597.Google Scholar
Wand, G. S., McCaul, M., Yang, X., Reynolds, J., Gotjen, D., Lee, S., et al. (2002). The mu-opioid receptor gene polymorphism (a118g) alters HPA axis activation induced by opioid receptor blockade. Neuropsychopharmacology, 26, 106–114.Google Scholar
Whale, R., Clifford, E. M., & Cowen, P. J. (2000). Does mirtazapine enhance serotonergic neurotransmission in depressed patients? Psychopharmacology (Berlin), 148, 325–326.Google Scholar
Willeit, M., Praschak-Rieder, N., Neumeister, A., Pirker, W., Asenbaum, S., Vitouch, O., et al. (2000). [123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biological Psychiatry, 47, 482–489.Google Scholar