Personality endophenotypes for bipolar affective disorder: A family-based genetic association analysis

Genes, Brain and Behavior

Volumn 7, Issue 8, 2008, Pages 869-876

  Savitz, J ^a   Van Der Merwe, L ^b   Ramesar, R ^a  

^a UNIVERSITY OF CAPE TOWN   (South Africa)

^b SOUTH AFRICAN MEDICAL RESEARCH COUNCIL   (South Africa)

Author keywords

BDNF; Bipolar disorder; COMT; Dopamine transporter (SLC6A3); Endophenotype; Personality; Serotonin transporter (SLC6A4); Temperament

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CATECHOL METHYLTRANSFERASE; SEROTONIN TRANSPORTER;

3' UNTRANSLATED REGION; ADULT; AFFECT; AGGRESSION; ALLELE; ANXIETY; ARTICLE; BIPOLAR DISORDER; CAUCASIAN; DYSTHYMIA; FAMILY; FEMALE; GENE STRUCTURE; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; HERITABILITY; HUMAN; IRRITABILITY; MAJOR CLINICAL STUDY; MALE; PERSONALITY; PHENOTYPE; PRIORITY JOURNAL; QUESTIONNAIRE; RELIGION; RISK FACTOR; TEMPERAMENT;

ADULT; AGED; BIPOLAR DISORDER; CATECHOL O-METHYLTRANSFERASE; COHORT STUDIES; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; FAMILY; FEMALE; GENE FREQUENCY; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INHERITANCE PATTERNS; LINKAGE DISEQUILIBRIUM; MALE; MIDDLE AGED; PERSONALITY; PERSONALITY INVENTORY; PHENOTYPE; POLYMORPHISM, GENETIC; PRINCIPAL COMPONENT ANALYSIS; QUESTIONNAIRES; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; TEMPERAMENT;

EID: 56749102735     PISSN: 16011848     EISSN: 1601183X     Source Type: Journal    
DOI: 10.1111/j.1601-183X.2008.00426.x     Document Type: Article

References (72)

1. Abecasis, G.R., Cookson, W.O. Cardon, L.R. (2000a) Pedigree tests of transmission disequilibrium. Eur J Hum Genet 8, 545 551.
2. Abecasis, G.R., Cardon, L.R. Cookson, W.O. (2000b) A general test of association for quantitative traits in nuclear families. Am J Hum Genet 66, 279 292.
3. Akiskal, H.S., Downs, J., Jordan, P., Watson, S., Daugherty, D. Pruitt, D.B. (1985) Affective disorders in referred children and younger siblings of manic-depressives. Mode of onset and prospective course. Arch Gen Psychiatry 42, 996 1003.
4. Akiskal, H.S., Akiskal, K.K., Haykal, R.F., Manning, J.S. Connor, P.D. (2005a) TEMPS-A: progress towards validation of a self-rated clinical version of the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire. J Affect Disord 85, 3 16.
5. Akiskal, H.S., Mendlowicz, M.V., Jean-Louis, G., Rapaport, M.H., Kelsoe, J.R., Gillin, J.C. Smith, T.L. (2005b) TEMPS-A: validation of a short version of a self-rated instrument designed to measure variations in temperament. J Affect Disord 85, 45 52.
6. de Almeida, R.M., Ferrari, P.F., Parmigiani, S. Miczek, K.A. (2005) Escalated aggressive behavior: dopamine, serotonin and GABA. Eur J Pharmacol 526, 51 64.
7. Altman, E.G., Hedeker, D., Peterson, J.L. Davis, J.M. (1997) The Altman Self-Rating Mania Scale. Biol Psychiatry 42, 948 955.
8. Bagby, R.M., Bindseil, K.D., Schuller, D.R., Rector, N.A., Young, L.T., Cooke, R.G., Seeman, M.V., McCay, E.A. Joffe, R.T. (1997) Relationship between the five-factor model of personality and unipolar, bipolar and schizophrenic patients. Psychiatry Res 70, 83 94.
9. Beck, A.T. Steer, R.A. (1993) Manual for the Beck Depression Inventory. The Psychological Corporation, San Antonio, TX.
10. Benjamin, J., Osher, Y., Kotler, M., Gritsenko, I., Nemanov, L., Belmaker, R.H. Ebstein, R.P. Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT). Mol Psychiatry 5, 96 100.
11. Bienvenu, O.J., Hettema, J.M., Neale, M.C., Prescott, C.A. Kendler, K.S. (2007) Low extraversion and high neuroticism as indices of genetic and environmental risk for social phobia, agoraphobia, and animal phobia. Am J Psychiatry 164, 1714 1721.
12. Cassano, G.B., Akiskal, H.S., Savino, M., Musetti, L. Perugi, G. (1992) Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament. J Affect Disord 26, 127 140.
13. Cho, H.J., Meira-Lima, I., Cordeiro, Q., Michelon, L., Sham, P., Vallada, H. Collier, D.A. (2005) Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis. Mol Psychiatry 10, 771 781.
14. Cloninger, C.R., Svrakic, D.M. Przybeck, T.R. (1993) A psychobiological model of temperament and character. Arch Gen Psychiatry 50, 975 990.
15. Collier, D.A., Stöber, G., Li, T., Heils, A., Catalano, M., Di Bella, D., Arranz, M.J., Murray, R.M., Vallada, H.P., Bengel, D., Mũller, C.R., Roberts, G.W., Smeraldi, E., Kirov, G., Sham, P. Lesch, K.P. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1, 453 460.
16. Dannlowski, U., Ohrmann, P., Bauer, J., Deckert, J., Hohoff, C., Kugel, H., Arolt, V., Heindel, W., Kersting, A., Baune, B.T. Suslow, T. (2007) 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology 33, 418 424.
17. Davis, K.L., Panksepp, J. Normansell, L. (2003) The affective neuroscience personality scales: normative data and implications. Neuro-Psychoanalysis 5, 57 69.
18. Ebstein, R.P. (2006) The molecular genetic architecture of human personality: beyond self-report questionnaires. Mol Psychiatry 11, 427 445.
19. Ebstein, R.P., Novick, O., Umansky, R., Priel, B., Osher, Y., Blaine, D., Bennett, E.R., Nemanov, L., Katz, M. Belmaker, R.H. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 12, 78 80.
20. Eckblad, M. Chapman, L.J. (1986) Development and validation of a scale for hypomanic personality. J Abnorm Psychol 95, 214 222.
21. Evans, L., Akiskal, H.S., Keck, P.E. Jr., McElroy, S.L., Sadovnick, A.D., Remick, R.A. Kelsoe, J.R. (2005) Familiality of temperament in bipolar disorder: support for a genetic spectrum. J Affect Disord 85, 153 168.
22. Filipenko, M.L., Alekseyenko, O.V., Beilina, A.G., Kamynina, T.P. Kudryavtseva, N.N. (2001) Increase of tyrosine hydroxylase and dopamine transporter mRNA levels in ventral tegmental area of male mice under influence of repeated aggression experience. Brain Res Mol Brain Res 96, 77 81.
23. Gerra, G., Garofano, L., Pellegrini, C., Bosari, S., Zaimovic, A., Moi, G., Avanzini, P., Talarico, E., Gardini, F. Donnini, C. (2005) Allelic association of a dopamine transporter gene polymorphism with antisocial behaviour in heroin-dependent patients. Addict Biol 10, 275 281.
24. Gottesman, II Gould, T.D. (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160, 636 645.
25. Greenwood, T.A., Alexander, M., Keck, P.E., McElroy, S., Sadovnick, A.D., Remick, R.A. Kelsoe, J.R. (2001) Evidence for linkage disequilibrium between the dopamine transporter and bipolar disorder. Am J Med Genet 105, 145 151.
26. Greenwood, T.A., Schork, N.J., Eskin, E. Kelsoe, J.R. (2006) Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples. Mol Psychiatry 11, 115.
27. Guo, G., Roettger, M.E. Shih, J.C. (2007) Contributions of the DAT1 and DRD2 genes to serious and violent delinquency among adolescents and young adults. Hum Genet 121, 125 136.
28. Hamer, D. (2004) The God Gene: How Faith is Hard-Wired into our Genes. Doubleday, New York, NY.
29. Hansenne, M., Delhez, M. Cloninger, C.R. (2005) Psychometric properties of the temperament and character inventory-revised (TCI-R) in a Belgian sample. J Pers Assess 85, 40 49.
30. Hantouche, E.G., Akiskal, H.S., Lancrenon, S., Allilaire, J.F., Sechter, D., Azorin, J.M., Bourgeois, M., Fraud, J.P. Chatenet-Duchene, L. (1998) Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP). J Affect Disord 50, 163 173.
31. Hariri, A.R., Mattay, V.S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M.F. Weinberger, D.R. (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400 403.
32. Hecht, H., van Calker, D., Berger, M. von Zerssen, D. (1998) Personality in patients with affective disorders and their relatives. J Affect Disord 51, 33 43.
33. Heinz, A., Braus, D.F., Smolka, M.N., Wrase, J., Puls, I., Hermann, D., Klein, S., Grusser, S.M., Flor, H., Schumann, G., Mann, K. Buchel, C. (2005) Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 8, 20 21.
34. Hunnerkopf, R., Strobel, A., Gutknecht, L., Brocke, B. Lesch, K.P. (2007) Interaction between BDNF Val66Met and dopamine transporter gene variation influences anxiety-related traits. Neuropsychopharmacology 32, 2552 2560.
35. Itoh, K., Hashimoto, K., Kumakiri, C., Shimizu, E. Iyo, M. (2004) Association between brain-derived neurotrophic factor 196 G/A polymorphism and personality traits in healthy subjects. Am J Med Genet B Neuropsychiatr Genet 124, 61 63.
36. Jorm, A.F., Prior, M., Sanson, A., Smart, D., Zhang, Y. Easteal, S. (2001) Association of a polymorphism of the dopamine transporter gene with externalizing behavior problems and associated temperament traits: a longitudinal study from infancy to the mid-teens. Am J Med Genet 105, 346 350.
37. Joyce, P.R., McHugh, P.C., McKenzie, J.M., Sullivan, P.F., Mulder, R.T., Luty, S.E., Carter, J.D., Frampton, C.M., Robert Cloninger, C., Miller, A.M. Kennedy, M.A. (2006) A dopamine transporter polymorphism is a risk factor for borderline personality disorder in depressed patients. Psychol Med 36, 807 813.
38. Kelsoe, J.R. (2003) Arguments for the genetic basis of the bipolar spectrum. J Affect Disord 73, 183 197.
39. Kelsoe, J.R., Sadovnick, A.D., Kristbjarnarson, H., Bergesch, P., Mroczkowski-Parker, Z., Drennan, M., Rapaport, M.H., Flodman, P., Spence, M.A. Remick, R.A. (1996) Possible locus for bipolar disorder near the dopamine transporter on chromosome 5. Am J Med Genet 67, 533 540.
40. Kieseppa, T., Partonen, T., Haukka, J., Kaprio, J. Lonnqvist, J. (2004) High concordance of bipolar I disorder in a nationwide sample of twins. Am J Psychiatry 161, 1814 1821.
41. Klein, D.N., Depue, R.A. Slater, J.F. (1986) Inventory identification of cyclothymia. IX. Validation in offspring of bipolar I patients. Arch Gen Psychiatry 43, 441 445.
42. Kuikka, J.T., Tiihonen, J., Bergstrom, K.A., Karhu, J., Rasanen, P. Eronen, M. (1998) Abnormal structure of human striatal dopamine re-uptake sites in habitually violent alcoholic offenders: a fractal analysis. Neurosci Lett 253, 195 197.
43. Lang, U.E., Hellweg, R., Kalus, P., Bajbouj, M., Lenzen, K.P., Sander, T., Kunz, D. Gallinat, J. (2005) Association of a functional BDNF polymorphism and anxiety-related personality traits. Psychopharmacology 180, 95 99.
44. Laucht, M., Skowronek, M.H., Becker, K., Schmidt, M.H., Esser, G., Schulze, T.G. Rietschel, M. (2007) Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample. Arch Gen Psychiatry 64, 585 590.
45. Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., Benjamin, J., Muller, C.R., Hamer, D.H. Murphy, D.L. (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527 1531.
46. Loftus, S.T., Garno, J.L., Jaeger, J. Malhotra, A.K. (2008) Temperament and character dimensions in bipolar I disorder: a comparison to healthy controls. J Psychiatr Res 42, 1131 1136.
47. López León, S., Croes, E.A., Sayed-Tabatabaei, F.A., Claes, S., Van Broeckhoven, C. van Duijn, C.M. The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysis. Biol Psychiatry 57, 999 1003.
48. Maier, W., Minges, J., Lichtermann, D., Franke, P. Gansicke, M. (1995) Personality patterns in subjects at risk for affective disorders. Psychopathology 28 (Suppl. 1 59 72.
49. Mansour, H.A., Talkowski, M.E., Wood, J. et al 2005) Serotonin gene polymorphisms and bipolar I disorder: focus on the serotonin transporter. Ann Med 37, 590 602.
50. Massat, I., Souery, D., Del-Favero, J., Nothen, M., Blackwood, D., Muir, W., Kaneva, R., Serretti, A., Lorenzi, C., Rietschel, M., Milanova, V., Papadimitriou, G.N., Dikeos, D., Van Broekhoven, C. Mendlewicz, J. (2005) Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in a European multicenter genetic association study. Mol Psychiatry 10, 598 605.
51. McGuffin, P., Rijsdijk, F., Andrew, M., Sham, P., Katz, R. Cardno, A. (2003) The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 60, 497 502.
52. Munafo, M.R., Bowes, L., Clark, T.G. Flint, J. (2005) Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol Psychiatry 10, 765 770.
53. Nery, F.G., Hatch, J.P., Glahn, D.C., Nicoletti, M.A., Serap Monkul, E., Najt, P., Fonseca, M., Bowden, C.L., Robert Cloninger, C. Soares, J.C. (2008) Temperament and character traits in patients with bipolar disorder and associations with comorbid alcoholism or anxiety disorders. J Psychiatr Res 42, 569 577.
54. Nowakowska, C., Strong, C.M., Santosa, C.M., Wang, P.W. Ketter, T.A. (2005) Temperamental commonalities and differences in euthymic mood disorder patients, creative controls, and healthy controls. J Affect Disord 85, 207 215.
55. Osher, Y., Cloninger, C.R. Belmaker, R.H. (1996) TPQ in euthymic manic-depressive patients. J Psychiatr Res 30, 353 357.
56. Pelissolo, A., Mallet, L., Baleyte, J.M., Michel, G., Cloninger, C.R., Allilaire, J.F. Jouvent, R. (2005) The temperament and character inventory-revised (TCI-R): psychometric characteristics of the French version. Acta Psychiatr Scand 112, 126 133.
57. Perugi, G., Akiskal, H.S., Lattanzi, L., Cecconi, D., Mastrocinque, C., Patronelli, A., Vignoli, S. Bemi, E. (1998) The high prevalence of "soft" bipolar (II) features in atypical depression. Compr Psychiatry 39, 63 71.
58. Pezawas, L., Meyer-Lindenberg, A., Drabant, E.M., Verchinski, B.A., Munoz, K.E., Kolachana, B.S., Egan, M.F., Mattay, V.S., Hariri, A.R. Weinberger, D.R. (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8, 828 834.
59. Rodriguiz, R.M., Chu, R., Caron, M.G. Wetsel, W.C. (2004) Aberrant responses in social interaction of dopamine transporter knockout mice. Behav Brain Res 148, 185 198.
60. Rowe, D.C., Stever, C., Gard, J.M., Cleveland, H.H., Sanders, M.L., Abramowitz, A., Kozol, S.T., Mohr, J.H., Sherman, S.L. Waldman, I.D. The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children. Behav Genet 28, 215 225.
61. Rozsa, S., Rihmer, Z., Gonda, X., Szili, I., Rihmer, A., Ko, N., Nemeth, A., Pestality, P., Bagdy, G., Alhassoon, O., Akiskal, K.K. Akiskal, H.S. (2008) A study of affective temperaments in Hungary: internal consistency and concurrent validity of the TEMPS-A against the TCI and NEO-PI-R. J Affect Disord 106, 45 53.
62. Savitz, J.B. Ramesar, R.S. (2004) Genetic variants implicated in personality: a review of the more promising candidates. Am J Med Genet B Neuropsychiatr Genet 131, 20 32.
63. Savitz, J.B. Ramesar, R.S. (2006) Personality: is it a viable endophenotype for genetic studies of bipolar affective disorder? Bipolar Disord 8, 322 337.
64. Savitz, J., Solms, M. Ramesar, R. (2005) Neuropsychological dysfunction in bipolar affective disorder: a critical opinion. Bipolar Disord 7, 216 235.
65. Savitz, J., Van der Merwe L. Ramesar R. (2008a) Dysthymic and anxiety-related personality traits in bipolar spectrum illness. J Affect Disord 109, 305 311.
66. Savitz, J., Van der Merwe, L. Ramesar, R. (2008b) Hypomanic, cyclothymic and hostile personality traits in bipolar spectrum illness: a family based study. J Psychiatr Res 42, 920 929.
67. Sen, S., Nesse, R.M., Stoltenberg, S.F., Li, S., Gleiberman, L., Chakravarti, A., Weder, A.B. Burmeister, M. (2003) A BDNF coding variant is associated with the NEO personality inventory domain neuroticism, a risk factor for depression. Neuropsychopharmacology 28, 397 401.
68. Shifman, S., Bronstein, M., Sternfeld, M., Pisante, A., Weizman, A., Reznik, I., Spivak, B., Grisaru, N., Karp, L., Schiffer, R., Kotler, M., Strous, R.D., Swartz-Vanetik, M., Knobler, H.Y., Shinar, E., Yakir, B., Zak, N.B. Darvasi, A. (2004) COMT: a common susceptibility gene in bipolar disorder and schizophrenia. Am J Med Genet B Neuropsychiatr Genet 128, 61 64.
69. Sklar, P., Gabriel, S.B., McInnis, M.G., Bennett, P., Lim, Y.M., Tsan, G., Schaffner, S., Kirov, G., Jones, I., Owen, M., Craddock, N., DePaulo, J.R. Lander, E.S. Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. Mol Psychiatry 7, 579 593.
70. Terwilliger, J.D. Goring, H.H. (2000) Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design. Hum Biol 72, 63 132.
71. Wigginton, J.E. Abecasis, G.R. (2005) PEDSTATS: descriptive statistics, graphics and quality assessment for gene mapping data. Bioinformatics 21, 3445 3447.
72. Young, S.E., Smolen, A., Corley, R.P., Krauter, K.S., DeFries, J.C., Crowley, T.J. Hewitt, J.K. (2002) Dopamine transporter polymorphism associated with externalizing behavior problems in children. Am J Med Genet 114, 144 149.