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The D2 dopamine receptor (DRD2) gene is associated with co-morbid depression, anxiety and social dysfunction in untreated veterans with post-traumatic stress disorder

Supported by The Greenslopes Private Hospital Research Foundation, Australia, Queensland University of Technology, Australia and the Adele C. Smithers-Fornaci and Christopher D. Smithers Foundation, United States

Published online by Cambridge University Press:  16 April 2020

Bruce R. Lawford ,
Ross Young ,
Ernest P. Noble ,
Burnett Kann  and
Terry Ritchie
Bruce R. Lawford
Affiliation:
Greenslopes Private Hospital, Brisbane, Qld., Australia Alcohol Research Centre, Neuropsychiatric Institute, UCLA, Los Angeles, CA, USA
Ross Young
Affiliation:
Alcohol Research Centre, Neuropsychiatric Institute, UCLA, Los Angeles, CA, USA School of Psychology and Counselling, Queensland University of Technology, Carseldine, Brisbane, Qld., Australia
Ernest P. Noble*
Affiliation:
Alcohol Research Centre, Neuropsychiatric Institute, UCLA, Los Angeles, CA, USA Brain Research Institute, UCLA, Los Angeles, CA, USA
Burnett Kann
Affiliation:
Nambour Hospital, Nambour, Qld., Australia
Terry Ritchie
Affiliation:
Alcohol Research Centre, Neuropsychiatric Institute, UCLA, Los Angeles, CA, USA
*
⁎Corresponding author. Present address: Pike Professor of Alcohol Studies, Alcohol Research Centre, Neuropsychiartric Institute (NPI), UCLA, Westwood, CA 90024, USA. E-mail address: epnoble@ucla.edu (E.P. Noble).
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Abstract

Objective.

To identify clusters of patients with post-traumatic stress disorder (PTSD) according to symptom profile and to examine the association of the A1 allele of the D2 dopamine receptor (DRD2) gene with these clusters.

Method.

Fifty-seven untreated Caucasian Vietnam veterans with PTSD were administered the General Health Questionnaire-28 (GHQ) and the Mississippi Scale for combat-related PTSD. DRD2 allelic status was determined by PCR.

Results.

Subjects with the DRD2 Al allele compared to those without this allele had significantly higher scores on GHQ 2 (anxiety/insomnia), GHQ 3 (social dysfunction) and GHQ 4 (depression). Cluster analysis of the GHQ data identified two primary groups. A high psychopathology cluster (cluster 3), featured by high co-morbid levels of somatic concerns, anxiety/insomnia, social dysfunction and depression, and a low psychopathology cluster (cluster 1), manifested by the reverse pattern. Scores in each of the four GHQ groups were significantly higher in cluster 3 than cluster 1, as was Mississippi Scale PTSD score. DRD2 A1 allele veterans compared to those without this allele were significantly more likely to be found in the high than the low psychopathology cluster group.

Conclusions.

DRD2 variants are associated with severe co-morbid psychopathology in PTSD subjects.

Keywords

PTSDDRD2 polymorphismAnxietyDepressionSocial dysfunction
Type
Original articles
Information
European Psychiatry , Volume 21 , Issue 3 , April 2006 , pp. 180 - 185
Copyright
Copyright © European Psychiatric Association 2006

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References

Ainsworth, K., Smith, S.E., Zetterstrom, T.S., Pei, Q., Franklin, M., Sharp, T.Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat. Psychopharmacology (Berl.) 1998;140:470–477.CrossRefGoogle ScholarPubMed
Bartoszyk, G.D.Anxiolytic effects of dopamine receptor ligands: I. Involvement of dopamine autoreceptors. Life Sci 1998;62:649–663.CrossRefGoogle ScholarPubMed
Berk, M.Selective serotonin reuptake inhibitors in mixed anxiety–depression. Int. Clin. Psychopharmacol 2000;15(Suppl 2):S41–S45.CrossRefGoogle ScholarPubMed
Berman, S.M., Noble, E.P.The D2 dopamine receptor (DRD2) gene and family stress; interactive effects on cognitive functions in children. Behav. Genet 1997;27:33–43.CrossRefGoogle ScholarPubMed
Bjelland, I., Dahl, A.A.Anxiety and depression—a common mixture. Tidsskr. Nor. Laegeforen 1999;119:3277–3280.Google ScholarPubMed
Bouras, N., Bridges, P.K.Bromocriptine in depression. Curr. Med. Res. Opin 1982;8:150–153.CrossRefGoogle ScholarPubMed
Bressan, R.A., Costa, D.C., Jones, H.M., Ell, P.J., Pilowsky, L.S.Typical antipsychotic drugs-D2 receptor occupancy and depressive symptoms in schizophrenia. Schizophr. Res 2002;56:31–36.CrossRefGoogle Scholar
de Haan, L., Lavalaye, J., Linszen, D., Dingemans, P.M., Booij, J.Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone. Am. J. Psychiatry 2000;157:1019–1020.CrossRefGoogle ScholarPubMed
Deahl, M.P., Gillham, A.B., Thomas, J., Searle, M.M., Srinivasin, M.Psychological sequelae following the Gulf war. Factors associated with subsequent morbidity and the effectiveness of psychological debriefing. Br. J. Psychiatry 1994;165:60–65.CrossRefGoogle ScholarPubMed
Dziedzicka-Wasylewska, M., Rogoz, R., Klimek, V., Maj, J.Repeated administration of antidepressant drugs affects the levels of mRNA coding for D1 and D2 dopamine receptors in the rat brain. J. Neural Transm 1997;10:515–524.CrossRefGoogle Scholar
Everitt, B.S., Landau, S., Leese, M.Cluster analysis. London: Edward Arnold; 2001.Google Scholar
Fuesner, J., Ritchie, T., Lawford, B., Young, R.M., Kann, B., Noble, E.P.GABA-A beta 3 subunit gene and psychiatric morbidity in a post-traumatic disorder stress population. Psychiatry Res 2001;104:109–117.CrossRefGoogle Scholar
Gingrich, B., Liu, Y., Cascio, C., Wang, Z., Insel, T.R.Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtos orchogaster). Behav. Neurosci 2000;114:173–183.CrossRefGoogle Scholar
Grandy, D.K., Zhang, Y., Civelli, O.PCR detection of the Taq A RFLP at the DRD2 locus. Hum. Mol. Genet 1993;2:2197.CrossRefGoogle Scholar
Hallman, W.K., Kipen, H.M., Diefenbach, M., Boyd, K., Kang, H., Leventhal, H., et al.Symptom patterns among Gulf war registry veterans. Am. J. Public Health 2003;93:624–630.CrossRefGoogle ScholarPubMed
Hill, S.Y., Zezza, N., Wipprecht, G., Locke, E., Neiswanger, K.Personality traits and dopamine receptors (D2 and D4): linkage studies in families of alcoholics. Am. J. Med. Genet 1999;88:634–641.3.0.CO;2-M>CrossRefGoogle Scholar
Koenen, K.C., Harley, R., Lyons, M.J., Wolfe, J., Simpson, J.C., Goldberg, J., et al.A twin registry study of familial and individual risk factors for trauma exposure and posttraumatic stress disorder. J. Nerv. Ment. Dis 2002;190(4):209–218.CrossRefGoogle ScholarPubMed
Jönsson, E.G., Nöthen, M.M., Grünhage, F., Farde, L., Nakashima, Y., Propping, P., et al.Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol. Psychiatry 1999;4:290–296.CrossRefGoogle ScholarPubMed
Kameda, K., Kusumi, I., Suzuki, K., Miura, J., Sasaki, Y., Koyama, T.Effects of citalopram on dopamine D2 receptor expression in the rat brain striatum. J. Mol. Neurosci 2000;14:77–86.CrossRefGoogle ScholarPubMed
Keane, T.M., Caddell, J.M., Taylor, K.L.Mississippi scale for combat-related post-traumatic stress disorder: three studies in reliability and validity. J. Consult. Clin. Psychol 1988;56:85–90.CrossRefGoogle ScholarPubMed
Kestler, L.P., Malhotra, A.K., Finch, C., Adler, C., Breier, A.The relation between dopamine D2 receptor density and personality: preliminary evidence from the NEO personality inventory-revised. Neuropsychiatry Neuropsychol. Behav. Neurol 2000;13:48–52.Google ScholarPubMed
Klimek, V., Schenck, J.E., Han, H., Stockmeier, C.A., Ordway, G.A.Dopaminergic abnormalities in amygdaloid nuclei in major depression: a post-mortem study. Biol. Psychiatry 2002;52:740–748.CrossRefGoogle Scholar
Klimke, A., Larisch, R., Janz, A., Vosberg, H., Muller-Gartner, H.W., Gaebel, W.Dopamine D2 receptor binding before and after treatment of major depression measured by [123I] IBZM SPECT. Psychiatry Res 1999;90(2):91–101.CrossRefGoogle Scholar
Kozaric-Kovacic, D., Hercigonja, D.K., Grubisic-Ilic, M.Posttraumatic stress disorder and depression in soldiers with combat experiences. Croat. Med. J 2001;42(2):165–170.Google ScholarPubMed
Lawford, B.R., Young, R., Noble, E.P., Kann, B., Arnold, L., Rowell, J., et al.D2 dopamine receptor gene polymorphism: paroxetine and social functioning in post-traumatic stress disorder. Eur. Neuropsychopharmacol 2003;13:313–320.CrossRefGoogle Scholar
Lawford, B.R., Young, R., Rowell, J.A., Qualichefski, J., Fletcher, B.H., Syndulko, K., et al.Bromocriptine in the treatment of alcoholics with the D2 dopamine receptor A1 allele. Nat. Med 1995;1:337–341.CrossRefGoogle ScholarPubMed
Marino, C., Vanzin, L., Giorda, R., Frigerio, A., Lorusso, M.L., Nobile, M., et al.An assessment of transmission disequilibrium between quantitative measures of childhood problem behaviors and DRD2/Taq1 and DRD4/48bp-repeat polymorphisms. Behav. Genet 2004;34:495–502.CrossRefGoogle Scholar
Miller, M.W., Greif, J.L., Smith, A.A.Multidimensional personality questionnaire profiles of veterans with traumatic combat exposure. Externalizing and Internalizing Subtypes. Psychol. Assess 2003;15(2):205–215.CrossRefGoogle ScholarPubMed
Nash, M.W., Huezo-Diaz, P., Williamson, R.J., Sterne, A., Purcell, S., Hoda, F., et al.Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships. Hum. Mol. Genet 2004;13:2173–2182.CrossRefGoogle ScholarPubMed
Noble, E.P., Blum, K., Ritchie, T., Montgomery, A., Sheridan, P.J.Allelic association of the D2 dopamine receptor gene with receptor binding characteristics in alcoholism. Arch. Gen. Psychiatry 1991;48:648–654.CrossRefGoogle ScholarPubMed
O'Toole, B.I., Marshall, R.P., Schureck, R.J., Dobson, M.Post-traumatic stress disorder and co-morbidity in Australian Vietnam veterans: risk factors, chronicity and combat. Aust. New Zealand J. Psychiatry 1998;32:32–42.CrossRefGoogle Scholar
Ormel, J., Koeter, M.W., Van der Brink, W., Giel, R.Concurrent validity of GHQ-28 and PSE as measures of change. Psychol. Med 1989;19:1007–1013.CrossRefGoogle ScholarPubMed
Pania, L., Gessab, G.L.Dopaminergic deficit and mood disorders. Int. Clin. Psychopharmacol 2002;(Suppl 4):S1–S7.Google ScholarPubMed
Pohjalainen, T., Rinne, J.O., Någren, K., Lehikoinen, P., Anttila, K., Syvalahti, E.K.G., et al.The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol. Psychiatry 1998;3:256–260.CrossRefGoogle ScholarPubMed
Rausch, J.L., Hobby, H.M., Shendarkar, N., Johnson, M.E., Li, J.Fluvoxamine treatment of mixed anxiety and depression: evidence for serotonergically medicate anxiolysis. J. Clin. Psychopharmocol 2001;21:139–142.CrossRefGoogle Scholar
Schneier, F.R., Blanco, C., Antia, S.X., Leibowitz, M.R.The social anxiety spectrum. Psychiatr. Clin. North Am 2002;25:757–774.CrossRefGoogle ScholarPubMed
Schneier, F.R., Leibowitz, M.R., Abi-Dargham, A., Zea-Ponce, Y., Lyn, S.H., Laurelle, M.Low dopamine D(2) receptor binding potential in social phobia. Am. J. Psychiatry 2001;158:327–328.CrossRefGoogle Scholar
Shively, C.A., Grant, K.A., Ehrenkaufer, R.L., Mach, R.H., Nader, M.A.Social stress, depression and brain dopamine in female cynomolgus monkeys. Ann. New York Acad. Sci 1997;807:574–577.CrossRefGoogle ScholarPubMed
Stein, M.B., Jang, K.L., Taylor, S., Vernon, P.A., Livesley, W.J.Genetic and environmental influences on trauma exposure and post-traumatic stress disorder symptoms: a twin study. Am. J. Psychiatry 2002;159:1675–1681.CrossRefGoogle ScholarPubMed
Theohar, C., Fischer-Comelssen, K., Brosch, H., Fischer, E.K., Petroic, D.A comparative, multicenter trial between bromocriptine and amitriptyline in the treatment of endogenous depression. Arzneimittelforschung 1982;32:783–787.Google ScholarPubMed
Thompson, J., Thomas, N., Singleton, A., Piggott, M., Lloyd, S., Perry, E.K., et al.D2 dopamine receptor gene (DRD2) TaqI A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 1997;7:479–484.CrossRefGoogle Scholar
Tremblay, L.K., Naranjo, C.A., Cardenas, L., Herrmann, N., Busto, U.E.2002. Probing brain reward system function in major depressive disorder: altered response to dextroamphetamine. Arch. Gen. Psychiatry 2002;59:409–416.CrossRefGoogle ScholarPubMed
True, W.R., Rice, J., Eisen, S.A., Heath, A.C., Goldberg, J., Lyons, M.J., et al.A twin study of genetic and environmental contributions to liability for post-traumatic stress symptoms. Arch. Gen. Psychiatry 1993;50:257–264.CrossRefGoogle Scholar
Volkow, N.D., Wang, G.J., Fowler, J.S., Logan, J., Gatley, S.J., Gifford, A., et al.Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels. Am. J. Psychiatry 1999;156:1440–1443.Google ScholarPubMed
Volkow, N.D., Wang, G.-J., Fowler, J.S., Thanos, T., Logan, J., Gatley, S.J., et al.Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study. Synapse 2002;46:79–82.CrossRefGoogle ScholarPubMed
Waehrens, J., Gerlach, J.Bromocriptine and imipramine in endogenous depression: a double-blind controlled trial in outpatients. J. Affect. Disord 1981;3:193–202.CrossRefGoogle Scholar
Ward, W.Psychiatric morbidity in Australian veterans of the United Nations peacekeeping force in Somalia. Aust. New Zealand J. Psychiatry 1997;31:184–193.CrossRefGoogle ScholarPubMed
Young, R.M., Lawford, B.R., Nutting, A., Noble, E.P.Advances in molecular genetics and the prevention and treatment of substance misuse: implications of association studies of the A1 allele of the D2 dopamine receptor genes. Addict. Behav 2004;29:1275–1294.CrossRefGoogle Scholar
Zatzick, D.F., Marmar, C.R., Weiss, D.S., Browner, W.S., Metzler, T.J., Golding, J.M., et al.Post-traumatic stress disorder and quality of life outcomes in a nationally representative sample of male Vietnam veterans. Am. J. Psychiatry 1997;154:1690–1695.CrossRefGoogle Scholar
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