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The Journal of Genetic Psychology
Research and Theory on Human Development
Volume 182, 2021 - Issue 3
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Research Articles

Variation rs6971 in the Translocator Protein Gene (TSPO) is Associated with Aggressiveness and Impulsivity but Not with Anxiety in a Population-Representative Sample of Young Adults

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Pages 149-162 | Received 05 Nov 2020, Accepted 24 Feb 2021, Published online: 26 Mar 2021

References

  • Akbari Balootbangan, A., & Talepasand, S. (2015). Validation of the Illinois bullying scale in primary school students of Semnan, Iran. Journal of Fundamentals of Mental Health, 17(4), 178–185.
  • Anholt, R. R., Pedersen, P. L., De Souza, E. B., & Snyder, S. H. (1986). The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane. The Journal of Biological Chemistry, 261(2), 576–583.
  • Berroterán-Infante, N., Tadić, M., Hacker, M., Wadsak, W., & Mitterhauser, M. (2019). Binding affinity of some endogenous and synthetic TSPO ligands regarding the rs6971 polymorphism. International Journal of Molecular Sciences, 20(3), 563. doi:10.3390/ijms20030563
  • Bevilacqua, L., & Goldman, D. (2013). Genetics of impulsive behaviour. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 368(1615), 20120380. doi:10.1098/rstb.2012.0380
  • Bonsack, F., & Sukumari-Ramesh, S. (2018). TSPO: An evolutionarily conserved protein with elusive functions. International Journal of Molecular Sciences, 19(6), 1694. doi:10.3390/ijms19061694
  • Book, A., Visser, B. A., Volk, A., Holden, R. R., & D’Agata, M. T. (2019). Ice and fire: Two paths to provoked aggression. Personality and Individual Differences, 138, 247–251. doi:10.1016/j.paid.2018.10.010
  • Bousardt, A. M. C., Hoogendoorn, A. W., Noorthoorn, E. O., Hummelen, J. W., & Nijman, H. L. I. (2016). Predicting inpatient aggression by self-reported impulsivity in forensic psychiatric patients. Criminal Behaviour and Mental Health, 26(3), 161–173. doi:10.1002/cbm.1955
  • Braestrup, C., & Squires, R. F. (1977). Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proceedings of the National Academy of Sciences of the United States of America, 74(9), 3805–3809. doi:10.1073/pnas.74.9.3805
  • Buss, A. H., & Perry, M. (1992). The aggression questionnaire. Journal of Personality and Social Psychology, 63(3), 452–452. doi:10.1037/0022-3514.63.3.452
  • Choi, H. B., Khoo, C., Ryu, J. K., Van Breemen, E., Kim, S. U., & McLarnon, J. G. (2002). Inhibition of lipopolysaccharide-induced cyclooxygenase-2, tumor necrosis factor-alpha and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195. Journal of Neurochemistry, 83(3), 546–555. doi:10.1046/j.1471-4159.2002.01122.x
  • Clark, W. R., & Grunstein, M. (2000). Are We Hardwired? The Role of Genes in Human Behaviour. New York: Oxford University Press.
  • Colasanti, A., Owen, D. R., Grozeva, D., Rabiner, E. A., Matthews, P. M., Craddock, N., & Young, A. H. (2013). Bipolar disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa translocator protein (TSPO). Psychoneuroendocrinology, 38(11), 2826–2829. doi:10.1016/j.psyneuen.2013.07.007
  • Cosenza‐Nashat, M., Zhao, M. L., Suh, H. S., Morgan, J., Natividad, R., Morgello, S., & Lee, S. C. (2009). Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathology and Applied Neurobiology, 35(3), 306–328. doi:10.1111/j.1365-2990.2008.01006.x
  • Costa, B., Pini, S., Gabelloni, P., Da Pozzo, E., Abelli, M., Lari, L., … Martini, C. (2009a). The spontaneous Ala147Thr amino acid substitution within the translocator protein influences pregnenolone production in lymphomonocytes of healthy individuals. Endocrinology, 150(12), 5438–5445. doi:10.1210/en.2009-0752
  • Costa, B., Pini, S., Martini, C., Abelli, M., Gabelloni, P., Landi, S., … Cassano, G. B. (2009b). Ala147thr substitution in translocator protein is associated with adult separation anxiety in patients with depression. Psychiatric Genetics, 19(2), 110–111. doi:10.1097/YPG.0b013e32832080f6
  • Craig, I. W., & Halton, K. E. (2009). Genetics of human aggressive behaviour. Human Genetics, 126(1), 101–113. doi:10.1007/s00439-009-0695-9
  • Dickman, S. J. (1990). Functional and dysfunctional impulsivity: Personality and cognitive correlates. Journal of Personality and Social Psychology, 58(1), 95–102. doi:10.1037/0022-3514.58.1.95
  • Espelage, D. L., & Holt, M. (2001). Bullying and victimization during early adolescence: Peer influences and psychosocial correlates. Journal of Emotional Abuse, 2(2–3), 123–142. doi:10.1300/J135v02n02_08
  • Ferrarese, C., Appollonio, I., Frigo, M., Perego, M., Piolti, R., Trabucchi, M., & Frattola, L. (1990). Decreased density of benzodiazepine receptors in lymphocytes of anxious patients: Reversal after chronic diazepam treatment. Acta Psychiatrica Scandinavica, 82(2), 169–173. doi:10.1111/j.1600-0447.1990.tb01376.x
  • Fite, P. J., Raine, A., Stouthamer-Loeber, M., Loeber, R., & Pardini, D. A. (2009). Reactive and proactive aggression in adolescent males: Examining differential outcomes 10 years later in early adulthood. Criminal Justice and Behavior, 37(2), 141–157. doi:10.1177/0093854809353051
  • Garofalo, C., Velotti, P., & Zavattini, G. C. (2018). Emotion regulation and aggression: The incremental contribution of alexithymia, impulsivity, and emotion dysregulation facets. Psychology of Violence, 8(4), 470–483. doi:10.1037/vio0000141
  • Gavish, M., Laor, N., Bidder, M., Fisher, D., Fonia, O., Muller, U., … Weizman, R. (1996). Altered platelet peripheral-type benzodiazepine receptor in posttraumatic stress disorder. Neuropsychopharmacology, 14(3), 181–186. doi:10.1016/0893-133X(95)00078-R
  • Harro, M., Eensoo, D., Kiive, E., Merenäkk, L., Alep, J., Oreland, L., & Harro, J. (2001). Platelet monoamine oxidase in healthy 9- and 15-years old children: The effect of gender, smoking and puberty. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25(8), 1497–1511. doi:10.1016/S0278-5846(01)00212-3
  • Johnson, M. R., Marazziti, D., Brawman-Mintzer, O., Emmanuel, N. P., Ware, M. R., Morton, W. A., … Lydiard, R. B. (1998). Abnormal peripheral benzodiazepine receptor density associated with generalized social phobia. Biological Psychiatry, 43(4), 306–309. doi:10.1016/S0006-3223(97)00390-9
  • Junck, L., Olson, J. M., Ciliax, B. J., Koeppe, R. A., Watkins, G. L., Jewett, D. M., … Mancini, W. R. (1989). PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site. Annals of Neurology, 26(6), 752–758. doi:10.1002/ana.410260611
  • Kiive, E., Laas, K., Vaht, M., Veidebaum, T., & Harro, J. (2017). Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 27(8), 816–827. doi:10.1016/j.euroneuro.2017.02.003
  • Laas, K., Kiive, E., Mäestu, J., Vaht, M., Veidebaum, T., & Harro, J. (2017). Nice guys: Homozygocity for the TPH2 -703G/T (rs4570625) minor allele promotes low aggressiveness and low anxiety . Journal of Affective Disorders, 215, 230–236. doi:10.1016/j.jad.2017.03.045
  • Laas, K., Reif, A., Akkermann, K., Kiive, E., Domschke, K., Lesch, K. P., … Harro, J. (2014). Interaction of the neuropeptide S receptor gene Asn107Ile variant and environment: Contribution to affective and anxiety disorders, and suicidal behaviour. The International Journal of Neuropsychopharmacology, 17(4), 541–552. doi:10.1017/S1461145713001478
  • Laas, K., Reif, A., Akkermann, K., Kiive, E., Domschke, K., Lesch, K. P., … Harro, J. (2015). Neuropeptide S receptor gene variant and environment: Contribution to alcohol use disorders and alcohol consumption. Addiction Biology, 20(3), 605–616. doi:10.1111/adb.12149
  • Laas, K., Reif, A., Herterich, S., Eensoo, D., Lesch, K. P., & Harro, J. (2010). The effect of a functional NOS1 promoter polymorphism on impulsivity is moderated by platelet MAO activity. Psychopharmacology, 209(3), 255–261. doi:10.1007/s00213-010-1793-z
  • Lacapere, J. J., & Papadopoulos, V. (2003). Peripheral-type benzodiazepine receptor: Structure and function of a cholesterol-binding protein in steroid and bile acid biosynthesis. Steroids, 68(7–8), 569–585. doi:10.1016/S0039-128X(03)00101-6
  • Lee, J. W., Nam, H., & Yu, S. W. (2016). Systematic analysis of translocator protein 18 kDa (TSPO) ligands on toll-like receptors-mediated pro-inflammatory responses in microglia and astrocytes. Experimental Neurobiology, 25(5), 262–268. doi:10.5607/en.2016.25.5.262
  • Li, H., & Papadopoulos, V. (1998). Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern . Endocrinology, 139(12), 4991–4997. doi:10.1210/endo.139.12.6390
  • Liu, J., Lewis, G., & Evans, L. (2013). Understanding aggressive behaviour across the lifespan. Journal of Psychiatric and Mental Health Nursing, 20(2), 156–168. doi:10.1111/j.1365-2850.2012.01902.x
  • Marazziti, D., Dell’Osso, B., Baroni, S., Masala, I., Di Nasso, E., Giannaccini, G., & Conti, L. (2005). Decreased density of peripheral benzodiazepine receptors in psychiatric patients after a suicide attempt. Life Sciences, 77(26), 3268–3275. doi:10.1016/j.lfs.2005.04.031
  • Marazziti, D., Rotondo, A., Martini, C., Giannaccini, G., Lucacchini, A., Pancioli-Guadagnucci, M. L., … Cassano, G. B. (1994). Changes in peripheral benzodiazepine receptors in patients with panic disorder and obsessive-compulsive disorder. Neuropsychobiology, 29(1), 8–11. doi:10.1159/000119055
  • Miczek, K. A., Fish, E. W., Joseph, F., & de Almeida, R. M. (2002). Social and neural determinants of aggressive behavior: Pharmacotherapeutic targets at serotonin, dopamine and gamma-aminobutyric acid systems. Psychopharmacology, 163(3–4), 434–458. doi:10.1007/s00213-002-1139-6
  • Miller, A. H., Haroon, E., & Felger, J. C. (2017). Therapeutic implications of brain-immune interactions: Treatment in translation. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 42(1), 334–359. doi:10.1038/npp.2016.167
  • Mizrahi, R., Rusjan, P. M., Kennedy, J., Pollock, B., Mulsant, B., Suridjan, I., … Houle, S. (2012). Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [(18)F]-FEPPA. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 32(6), 968–972. doi:10.1038/jcbfm.2012.46
  • Moeller, F. G., Barratt, E. S., Dougherty, D. M., Schmitz, J. M., & Swann, A. C. (2001). Psychiatric aspects of impulsivity. The American Journal of Psychiatry, 158(11), 1783–1793. doi:10.1176/appi.ajp.158.11.1783
  • Mondelli, V., Vernon, A. C., Turkheimer, F., Dazzan, P., & Pariante, C. M. (2017). Brain microglia in psychiatric disorders. The Lancet. Psychiatry, 4(7), 563–572. doi:10.1016/S2215-0366(17)30101-3
  • Nakamura, K., Yamada, K., Iwayama, Y., Toyota, T., Furukawa, A., Takimoto, T., … Mori, N. (2006). Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics, 141B(3), 222–226. doi:10.1002/ajmg.b.30211
  • Nelson, R. J., & Trainor, B. C. (2007). Neural mechanisms of aggression. Nature Reviews. Neuroscience, 8(7), 536–546. doi:10.1038/nrn2174
  • Nestor, P. G. (2002). Mental disorder and violence: Personality dimensions and clinical features. The American Journal of Psychiatry, 159(12), 1973–1978. doi:10.1176/appi.ajp.159.12.1973
  • Neumann, I. D., Veenema, A. H., & Beiderbeck, D. I. (2010). Aggression and anxiety: Social context and neurobiological links. Frontiers in Behavioral Neuroscience, 4, 12. doi:10.3389/fnbeh.2010.00012
  • Nothdurfter, C., Baghai, T. C., Schüle, C., & Rupprecht, R. (2012). Translocator protein (18 kDa)(TSPO) as a therapeutic target for anxiety and neurologic disorders. European Archives of Psychiatry and Clinical Neuroscience, 262(S2), 107–112. doi:10.1007/s00406-012-0352-5
  • Notter, T., Schalbetter, S. M., Clifton, N. E., Mattei, D., Richetto, J., Thomas, K., … Hall, J. (2020). Neuronal activity increases translocator protein (TSPO) levels. Molecular Psychiatry, 12(1), 3. doi:10.1038/mp.2017.232
  • Notter, T., Coughlin, J. M., Sawa, A., & Meyer, U. (2018). Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry. Mol Psychiatry, 23(1), 36–47. doi:10.1038/mp.2017.232
  • Nudmamud, S., Siripurkpong, P., Chindaduangratana, C., Harnyuttanakorn, P., Lotrakul, P., Laarbboonsarp, W., … Casalotti, S. O. (2000). Stress, anxiety and peripheral benzodiazepine receptor mRNA levels in human lymphocytes. Life Sciences, 67(18), 2221–2231. doi:10.1016/S0024-3205(00)00806-7
  • Owen, D. R., Fan, J., Campioli, E., Venugopal, S., Midzak, A., Daly, E., … Papadopoulos, V. (2017). TSPO mutations in rats and a human polymorphism impair the rate of steroid synthesis. The Biochemical Journal, 474(23), 3985–3999. doi:10.1042/BCJ20170648
  • Owen, D. R., Yeo, A. J., Gunn, R. N., Song, K., Wadsworth, G. C., Lewis, A. E., … Rubio, J. A. (2012). An 18-kDa Translocator Protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 32(1), 1–5. doi:10.1038/jcbfm.2011.147
  • Paaver, M., Kurrikoff, T., Nordquist, N., Oreland, L., & Harro, J. (2008). The effect of 5-HTT gene promoter polymorphism on impulsivity depends on family relations in girls. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32(5), 1263–1268. doi:10.1016/j.pnpbp.2008.03.021
  • Paaver, M., Nordquist, N., Parik, J., Harro, M., Oreland, L., & Harro, J. (2007). Platelet MAO activity and the 5-HTT gene promoter polymorphism are associated with impulsivity and cognitive style in visual information processing. Psychopharmacology, 194(4), 545–554. doi:10.1007/s00213-007-0867-z
  • Papadopoulos, V., Aghazadeh, Y., Fan, J., Campioli, E., Zirkin, B., & Midzak, A. (2015). Translocator protein-mediated pharmacology of cholesterol transport and steroidogenesis. Molecular and Cellular Endocrinology, 408, 90–98. doi:10.1016/j.mce.2015.03.014
  • Papadopoulos, V., Baraldi, M., Guilarte, T. R., Knudsen, T. B., Lacapère, J. J., Lindemann, P., … Gavish, M. (2006). Translocator protein (18kDa): New nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends in Pharmacological Sciences, 27(8), 402–409. doi:10.1016/j.tips.2006.06.005
  • Papadopoulos, V., Fan, J., & Zirkin, B. (2018). Translocator protein (18 kDa): An update on its function in steroidogenesis. Journal of Neuroendocrinology, 30(2), e12500. doi:10.1111/jne.12500
  • Pape, K., Tamouza, R., Leboyer, M., & Zipp, F. (2019). Immunoneuropsychiatry - Novel perspectives on brain disorders. Nature Reviews. Neurology, 15(6), 317–328. doi:10.1038/s41582-019-0174-4
  • Paquin, S., Lacourse, E., Brendgen, M., Vitaro, F., Dionne, G., Tremblay, R. E., & Boivin, M. (2017). Heterogeneity in the development of proactive and reactive aggression in childhood: Common and specific genetic - environmental factors. PLoS One, 12(12), e0188730. doi:10.1371/journal.pone.0188730
  • Patel, J., & Marangos, P. J. (1982). Differential effects of GABA on peripheral and central type benzodiazepine binding sites in brain. Neuroscience Letters, 30(2), 157–160. doi:10.1016/0304-3940(82)90289-0
  • Patton, J. H., Stanford, M. S., & Barratt, E. S. (1995). Factor structure of the Barratt impulsiveness scale. Journal of Clinical Psychology, 51(6), 768–774. doi:10.1002/1097-4679(199511)51:6 < 768::AID-JCLP2270510607 > 3.0.CO;2-1
  • Pavlov, K. A., Chistiakov, D. A., & Chekhonin, V. P. (2012). Genetic determinants of aggression and impulsivity in humans. Journal of Applied Genetics, 53(1), 61–82. doi:10.1007/s13353-011-0069-6
  • Pibiri, F., Nelson, M., Carboni, G., & Pinna, G. (2006). Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids. Neuroreport, 17(14), 1537–1541. doi:10.1097/01.wnr.0000234752.03808.b2
  • Pinna, G., Dong, E., Matsumoto, K., Costa, E., & Guidotti, A. (2003). In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine. Proceedings of the National Academy of Sciences of the United States of America, 100(4), 2035–2040. doi:10.1073/pnas.0337642100
  • Prossin, A. R., Chandler, M., Ryan, K. A., Saunders, E. F., Kamali, M., Papadopoulos, V., … McInnis, M. G. (2018). Functional TSPO polymorphism predicts variance in the diurnal cortisol rhythm in bipolar disorder. Psychoneuroendocrinology, 89, 194–202. doi:10.1016/j.psyneuen.2018.01.013
  • Richards, J. G., & Mohler, H. (1984). Benzodiazepine receptors. Neuropharmacology, 23(2B), 233–242. doi:10.1016/0028-3908(84)90064-9
  • Rocca, P., Ravizza, L., Maina, G., Bergamasco, B., & Ferrero, P. (1992). Peripheral-type benzodiazepine receptors in blood cells of anxious patients. Advances in Biochemical Psychopharmacology, 47, 229–233.
  • Schoemaker, H., Morelli, M., Deshmukh, P., & Yamamura, H. I. (1982). [3H] Ro5-4864 benzodiazepine binding in the kainate lesioned striatum and Huntington's diseased basal ganglia. Brain Research, 248(2), 396–401. doi:10.1016/0006-8993(82)90602-3
  • Schüle, C., Nothdurfter, C., & Rupprecht, R. (2014). The role of allopregnanolone in depression and anxiety. Progress in Neurobiology, 113, 79–87. doi:10.1016/j.pneurobio.2013.09.003
  • Séguin, J., & Zelazo, P. (2005). Executive function in early physical aggression. In R. E. Tremblay, W. W. Hartup, & J. Archer (Eds.), Developmental origins of aggression (pp. 307–329). New York: Guilford.
  • Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., … Dunbar, G. C. (1998). The Mini International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-VI and ICD-10. The Journal of Clinical Psychiatry, 59, 22–33.
  • Shlik, J., Aluoja, A., & Kihl, E. (1999). MINI 5.0.0. Mini rahvusvaheline neuropsühhiaatriline intervjuu DSM–IV. Estonian version of MINI international neuropsychiatric interview.
  • Soma, K. K., Scotti, M. A., Newman, A. E., Charlier, T. D., & Demas, G. E. (2008). Novel mechanisms for neuroendocrine regulation of aggression. Frontiers in Neuroendocrinology, 29(4), 476–489. doi:10.1016/j.yfrne.2007.12.003
  • Spielberger, C. D., Gorsuch, R. L., Lushene, R., Vagg, P. R., & Jacobs, G. A. (1983). Manual for the state-trait anxiety inventory. Palo Alto (CA): Consulting Psychology Press.
  • Tallman, J. F., Thomas, J. W., & Gallager, D. W. (1978). GABAergic modulation of benzodiazepine binding site sensitivity. Nature, 274(5669), 383–385. doi:10.1038/274383a0
  • Tonnaer, F., Cima, M., & Arntz, A. (2016). Executive (dys)functioning and impulsivity as possible vulnerability factors for aggression in forensic patients. The Journal of Nervous and Mental Disease, 204(4), 280–286. doi:10.1097/NMD.0000000000000485
  • Veiga, S., Carrero, P., Pernia, O., Azcoitia, I., & Garcia‐Segura, L. M. (2007). Translocator protein 18 kDa is involved in the regulation of reactive gliosis. Glia, 55(14), 1426–1436. doi:10.1002/glia.20558

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