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The dopamine transporter gene possibly affects personality traits in patients with early-onset major depressive disorder

Published online by Cambridge University Press:  12 March 2013

Chang-Chih Huang ,
Ru-Band Lu ,
Mei-Chen Shih ,
Che-Hung Yen  and
San-Yuan Huang
Chang-Chih Huang
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C. Department of Psychiatry, Taoyuan Armed Forces General Hospital, Taoyuan, R.O.C.
Ru-Band Lu
Affiliation:
Department of Psychiatry, Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, R.O.C.
Mei-Chen Shih
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Che-Hung Yen
Affiliation:
Department of Neurology, Tri-Service General Hospital, Taipei, R.O.C.
San-Yuan Huang*
Affiliation:
Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
*
Dr. San-Yuan Huang, Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng-Kung Road, Sec. 2, Nei-Hu District, Taipei 114, Taiwan, R.O.C. Tel: +011-886-2-8792-7220; Fax: +011-886-2-8792-7221; E-mail: hsy@ndmctsgh.edu.tw
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Abstract

Objective

Comorbid personality pathologies may affect the outcome of patients with major depression (MD). The dopamine transporter gene DAT1 (SLC6A3) has been suggested to play a role in both depression and specific personality traits. The aim of this study was to assess five polymorphisms of the DAT1 gene (rs2550948, rs2975226, rs6347, rs27072, and 3′-VNTR) to determine whether this gene influences personality traits in patients with MD or its subgroups.

Methods

The DAT1 polymorphisms were analysed in 463 unrelated Han Chinese MD patients. The personality traits, novelty seeking (NS), and harm avoidance (HA), were examined using the Tridimensional Personality Questionnaire. The patients were also divided into four clinical subgroups on the basis of differences in their sex (male or female) and age at disease onset (early or late).

Results

There was no association between the DAT1 gene and either NS or HA in the total MD sample or in the sex-based subgroups. However, early-onset MD patients with the G/G genotype of rs2550948 and the T/T genotype of rs2975226 had lower NS scores than did patients with the other genotypes (pcorrected = 0.05 for rs2550948 and pcorrected = 0.005 for rs2975226).

Conclusion

Our study suggests that DAT1 promoter variants possibly influence specific personality traits in the early-onset subgroup of depressed patients in the Han Chinese population. Further prospective cohort studies are required to verify our preliminary finding and to confirm the effects of personality susceptibility on long-term disease outcomes.

Keywords

DAT1depressiondopamine transporterearly onsetpersonality
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 4 , August 2013 , pp. 227 - 234
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

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References

1.Mulder, RT. Personality pathology and treatment outcome in major depression: a review. Am J Psychiatry 2002;159:359–371.Google Scholar
2.Cloninger, CR. A systematic method for clinical description and classification of personality variants. A proposal. Arch Gen Psychiatry 1987;44:573–588.Google Scholar
3.Celikel, FC, Kose, S, Cumurcu, BEet al. Cloninger's temperament and character dimensions of personality in patients with major depressive disorder. Compr Psychiatry 2009;50:556–561.Google Scholar
4.Farmer, A, Mahmood, A, Redman, K, Harris, T, Sadler, S, McGuffin, P. A sib-pair study of the temperament and character inventory scales in major depression. Arch Gen Psychiatry 2003;60:490–496.Google Scholar
5.Richter, J, Eisemann, M, Richter, G. Temperament and character during the course of unipolar depression among inpatients. Eur Arch Psychiatry Clin Neurosci 2000;250:40–47.CrossRefGoogle ScholarPubMed
6.Hansenne, M, Reggers, J, Pinto, E, Kjiri, K, Ajamier, A, Ansseau, M. Temperament and character inventory (TCI) and depression. J Psychiatr Res 1999;33:31–36.Google Scholar
7.Joffe, RT, Bagby, RM, Levitt, AJ, Regan, JJ, Parker, JD. The Tridimensional Personality Questionnaire in major depression. Am J Psychiatry 1993;150:959–960.Google Scholar
8.Hansenne, M, Pitchot, W, Gonzalez Moreno, A, Machurot, PY, Ansseau, M. The tridimensional personality questionnaire (TPQ) and depression. Eur Psychiatry 1998;13:101–103.Google Scholar
9.Stedenfeld, KA, Clinton, SM, Kerman, IA, Akil, H, Watson, SJ, Sved, AF. Novelty-seeking behavior predicts vulnerability in a rodent model of depression. Physiol Behav 2011;103:210–216.CrossRefGoogle Scholar
10.Csorba, J, Dinya, E, Ferencz, E, Steiner, P, Bertalan, G, Zsadon, A. Novelty seeking: difference between suicidal and non-suicidal Hungarian adolescent outpatients suffering from depression. J Affect Disord 2010;120:217–220.Google Scholar
11.Heck, A, Lieb, R, Ellgas, Aet al. Investigation of 17 candidate genes for personality traits confirms effects of the HTR2A gene on novelty seeking. Genes Brain Behav 2009;8:464–472.Google Scholar
12.Reif, A, Lesch, KP. Toward a molecular architecture of personality. Behav Brain Res 2003;139:1–20.Google Scholar
13.Shibuya, N, Kamata, M, Suzuki, A, Matsumoto, Y, Goto, K, Otani, K. The -67 A/T promoter polymorphism in the dopamine transporter gene affects personality traits of Japanese healthy females. Behav Brain Res 2009;203:23–26.Google Scholar
14.Joyce, PR, Mchugh, PC, Light, KJ, Rowe, S, Miller, AL, Kennedy, MA. Relationships between angry-impulsive personality traits and genetic polymorphisms of the dopamine transporter. Biol Psychiatry 2009;66:717–721.Google Scholar
15.Nutt, DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 2006;67(Suppl. 6):3–8.Google ScholarPubMed
16.Giros, B, Caron, MG. Molecular characterization of the dopamine transporter. Trends Pharmacol Sci 1993;14:43–49.CrossRefGoogle ScholarPubMed
17.Huang, SY, Chen, HK, Ma, KHet al. Association of promoter variants of human dopamine transporter gene with schizophrenia in Han Chinese. Schizophr Res 2010;116:68–74.Google Scholar
18.Mick, E, Kim, JW, Biederman, Jet al. Family based association study of pediatric bipolar disorder and the dopamine transporter gene (SLC6A3). Am J Med Genet B Neuropsychiatr Genet 2008;147B:1182–1185.CrossRefGoogle ScholarPubMed
19.Sharp, SI, Mcquillin, A, Gurling, HM. Genetics of attention-deficit hyperactivity disorder (ADHD). Neuropharmacology 2009;57:590–600.CrossRefGoogle ScholarPubMed
20.Vanness, SH, Owens, MJ, Kilts, CD. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet 2005;6:55.CrossRefGoogle ScholarPubMed
21.Mill, J, Asherson, P, Browes, C, D'Souza, U, Craig, I. Expression of the dopamine transporter gene is regulated by the 3′ UTR VNTR: evidence from brain and lymphocytes using quantitative RT-PCR. Am J Med Genet 2002;114:975–979.Google Scholar
22.van de Giessen, EM, de Win, MM, Tanck, MW, van den Brink, W, Baas, F, Booij, J. Striatal dopamine transporter availability associated with polymorphisms in the dopamine transporter gene SLC6A3. J Nucl Med 2009;50:45–52.Google Scholar
23.Rubie, C, Schmidt, F, Knapp, Met al. The human dopamine transporter gene: the 5′-flanking region reveals five diallelic polymorphic sites in a Caucasian population sample. Neurosci Lett 2001;297:125–128.Google Scholar
24.Bamne, MN, Talkowski, ME, Chowdari, KV, Nimgaonkar, VL. Functional analysis of upstream common polymorphisms of the dopamine transporter gene. Schizophr Bull 2009;36:977–982.CrossRefGoogle ScholarPubMed
25.Kelada, SN, Costa-Mallen, P, Checkoway, Het al. Dopamine transporter (SLC6A3) 5′ region haplotypes significantly affect transcriptional activity in vitro but are not associated with Parkinson's disease. Pharmacogenet Genomics 2005;15:659–668.Google Scholar
26.Suhara, T, Yasuno, F, Sudo, Yet al. Dopamine D2 receptors in the insular cortex and the personality trait of novelty seeking. Neuroimage 2001;13:891–895.Google Scholar
27.Kim, JH, Son, YD, Kim, HKet al. Association of harm avoidance with dopamine D(2/3) receptor availability in striatal subdivisions: a high resolution PET study. Biol Psychol 2011;87:164–167.Google Scholar
28.Yasuno, F, Suhara, T, Sudo, Yet al. Relation among dopamine D(2) receptor binding, obesity and personality in normal human subjects. Neurosci Lett 2001;300:59–61.Google Scholar
29.Anghelescu, I, Klawe, C, Singer, Pet al. Low novelty seeking and high self directedness scores in alcohol-dependent patients without comorbid psychiatric disorders homozygous for the A10 allele of the dopamine transporter gene. World J Biol Psychiatry 2010;11:382–389.Google Scholar
30.Savitz, J, van der Merwe, L, Ramesar, R. Personality endophenotypes for bipolar affective disorder: a family-based genetic association analysis. Genes Brain Behav 2008;7:869–876.CrossRefGoogle ScholarPubMed
31.Manki, H, Kanba, S, Muramatsu, Tet al. Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders. J Affect Disord 1996;40:7–13.Google Scholar
32.Frisch, A, Postilnick, D, Rockah, Ret al. Association of unipolar major depressive disorder with genes of the serotonergic and dopaminergic pathways. Mol Psychiatry 1999;4:389–392.Google Scholar
33.Huang, CC, Lu, RB, Shih, MC, Yen, CH, Huang, SY. Association study of the dopamine transporter gene with personality traits and major depressive disorder in the Han Chinese population. Pharmacogenet Genomics 2011;21:94–97.Google Scholar
34.Endicott, J, Spitzer, RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978;35:837–844.CrossRefGoogle ScholarPubMed
35.Merikangas, KR, Stevens, DE, Fenton, Bet al. Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychol Med 1998;28:773–788.Google Scholar
36.Huang, SY, Lin, WW, Ko, HCet al. Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence. Alcohol Clin Exp Res 2004;28:374–384.Google Scholar
37.Chen, WJ, Chen, HM, Chen, CC, Yu, WY, Cheng, AT. Cloninger's Tridimensional Personality Questionnaire: psychometric properties and construct validity in Taiwanese adults. Compr Psychiatry 2002;43:158–166.Google Scholar
38.Marazita, ML, Neiswanger, K, Cooper, Met al. Genetic segregation analysis of early-onset recurrent unipolar depression. Am J Hum Genet 1997;61:1370–1378.Google Scholar
39.Huang, SY, Lin, WW, Wan, FJet al. Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence. J Psychiatry Neurosci 2007;32:185–192.Google Scholar
40.Buchner, A, Faul, F, Erdfelder, E. G-power: a priori, post hoc, and compromise power analyses for the Macintosh, version 2.1.1 . Trier, Germany: University of Trier, 1996.Google Scholar
41.Mozley, LH, Gur, RC, Mozley, PD, Gur, RE. Striatal dopamine transporters and cognitive functioning in healthy men and women. Am J Psychiatry 2001;158:1492–1499.Google Scholar
42.Glenthoj, BY, Mackeprang, T, Svarer, Cet al. Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender. Biol Psychiatry 2006;60:621–629.CrossRefGoogle ScholarPubMed
43.Saint Arnault, D, Sakamoto, S, Moriwaki, A. The association between negative self-descriptions and depressive symptomology: does culture make a difference? Arch Psychiatr Nurs 2005;19:93–100.Google Scholar
44.Rush, AJ. The varied clinical presentations of major depressive disorder. J Clin Psychiatry 2007;68(Suppl. 8):4–10.Google Scholar
45.Akiskal, HS, Maser, JD, Zeller, PJet al. Switching from ‘unipolar’ to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995;52:114–123.Google Scholar
46.Coryell, W, Endicott, J, Keller, MB. Predictors of relapse into major depressive disorder in a nonclinical population. Am J Psychiatry 1991;148:1353–1358.Google Scholar
47.Agosti, V, Hellerstein, DJ, Stewart, JW. Does personality disorder decrease the likelihood of remission in early-onset chronic depression? Compr Psychiatry 2009;50:491–495.Google Scholar
48.Zubenko, GS, Zubenko, WN, Spiker, DG, Giles, DE, Kaplan, BB. Malignancy of recurrent, early-onset major depression: a family study. Am J Med Genet 2001;105:690–699.Google Scholar
49.Jylha, P, Mantere, O, Melartin, Tet al. Differences in temperament and character dimensions in patients with bipolar I or II or major depressive disorder and general population subjects. Psychol Med 2011;41:1579–1591.Google Scholar
50.Smith, DJ, Duffy, L, Stewart, ME, Muir, WJ, Blackwood, DH. High harm avoidance and low self-directedness in euthymic young adults with recurrent, early-onset depression. J Affect Disord 2005;87:83–89.CrossRefGoogle ScholarPubMed
51.Ongur, D, Farabaugh, A, Iosifescu, DV, Perlis, R, Fava, M. Tridimensional personality questionnaire factors in major depressive disorder: relationship to anxiety disorder comorbidity and age of onset. Psychother Psychosom 2005;74:173–178.CrossRefGoogle ScholarPubMed