The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males

Bipolar Disorders

Volumn 13, Issue 3, 2011, Pages 250-259

  Roussos, Panos ^a,b   Giakoumaki, Stella G ^a   Georgakopoulos, Anastasios ^b   Robakis, Nikolaos K ^b   Bitsios, Panos ^a  

^a UNIVERSITY OF CRETE   (Greece)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Bipolar disorder; Endophenotypes; Genetics; Prepulse inhibition; Schizophrenia; Startle

Indexed keywords

ADULT; ANK3 GENE; ANXIETY; ARTICLE; CACNA1C GENE; COGNITION; COHORT ANALYSIS; GENE; GENETIC RISK; HUMAN; HUMAN EXPERIMENT; MALE; NEUROPSYCHOLOGY; NORMAL HUMAN; PARANOIA; PERSONALITY; PHENOTYPE; PREPULSE INHIBITION; PRIORITY JOURNAL; STARTLE REFLEX;

ADOLESCENT; ADULT; ALLELES; ANALYSIS OF VARIANCE; ANKYRINS; CALCIUM CHANNELS, L-TYPE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; GREECE; HUMANS; MALE; MILITARY PERSONNEL; MOOD DISORDERS; NEUROPSYCHOLOGICAL TESTS; PERSONALITY; PERSONALITY INVENTORY; POLYMORPHISM, SINGLE NUCLEOTIDE; RISK FACTORS; SENSORY GATING; STARTLE REACTION; YOUNG ADULT;

EID: 79959249145     PISSN: 13985647     EISSN: 13995618     Source Type: Journal    
DOI: 10.1111/j.1399-5618.2011.00924.x     Document Type: Article

References (102)

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Press, 1994.
2. McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry 2003; 60: 497-502.
3. Berrettini WH. Are schizophrenic and bipolar disorders related? A review of family and molecular studies. Biol Psychiatry 2000; 48: 531-538.
4. Craddock N, Owen MJ. The beginning of the end for the Kraepelinian dichotomy. Br J Psychiatry 2005; 186: 364-366.
5. Lichtenstein P, Yip BH, Björk C et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 2009; 373: 234-239.
6. Ferreira MA, O'Donovan MC, Meng YA et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40: 1056-1058.
7. Wellcome Trust Case Control Consortium. Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. Nature 2007; 447: 661-678.
8. Sklar P, Smoller JW, Fan J et al. Whole-genome association study of bipolar disorder. Mol Psychiatry 2008; 13: 558-569.
9. Green EK, Grozeva D, Jones I et al. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 2010; 15: 1016-1022.
10. Splawski I, Timothy KW, Priori SG, Napolitano C, Bloise R. Timothy Syndrome. In: Pagon RA, Bird TD, Dolan CR, Stephens K eds. GeneReviews [Internet]. Seattle: University of Washington, Seattle, 1993.
11. Kordeli E, Lambert S, Bennett V. Ankyrin G. A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J Biol Chem 1995; 270: 2352-2359.
12. Zhou D, Lambert S, Malen PL, Carpenter S, Boland LM, Bennett V. AnkyrinG is required for clustering of voltage-gated Na channels at axon initial segments and for normal action potential firing. J Cell Biol 1998; 143: 1295-1304.
13. Barnett JH, Smoller JW. The genetics of bipolar disorder. Neuroscience 2009; 164: 331-343.
14. Krug A, Nieratschker V, Markov V et al. Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals. Neuroimage 2010; 49: 1831-1836.
15. Erk S, Meyer-Lindenberg A, Schnell K et al. Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry 2010; 67: 803-811.
16. Bigos K, Mattay V, Callicott J et al. Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 2010; 67: 939-945.
17. Stefanopoulou E, Manoharan A, Landau S, Geddes JR, Goodwin G, Frangou S. Cognitive functioning in patients with affective disorders and schizophrenia: a meta-analysis. Int Rev Psychiatry 2009; 21: 336-356.
18. Thaker GK. Neurophysiological endophenotypes across bipolar and schizophrenia psychosis. Schizophr Bull 2008; 34: 760-773.
19. Giakoumaki SG, Roussos P, Rogdaki M, Karli C, Bitsios P, Frangou S. Evidence of disrupted prepulse inhibition in unaffected siblings of bipolar disorder patients. Biol Psychiatry 2007; 62: 1418-1422.
20. Savitz JB, Ramesar RS. Personality: is it a viable endophenotype for genetic studies of bipolar affective disorder? Bipolar Disord 2006; 8: 322-337.
21. Smith MJ, Cloninger CR, Harms MP, Csernansky JG. Temperament and character as schizophrenia-related endophenotypes in non-psychotic siblings. Schizophr Res 2008; 104: 198-205.
22. Roussos P, Giakoumaki S, Adamaki E, Bitsios P. The influence of schizophrenia-related neuregulin-1 polymorphisms on sensorimotor gating in healthy males. Biol Psychiatry 2011; 69: 479-486.
23. Sheehan DV, Lecrubier Y, Sheehan KH et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59 (Suppl. 20): 22-33.
24. Sahakian BJ, Owen AM. Computerized assessment in neuropsychiatry using CANTAB: discussion paper. J R Soc Med 1992; 85: 399-402.
25. Cohen JD, Perlstein WM, Braver TS et al. Temporal dynamics of brain activation during a working memory task. Nature 1997; 386: 604-608.
26. Wechsler D. WAIS-III WMS-III: Technical Manual. San Antonio: Psychological Corporation, 1997.
27. Eysenck H, Eysenck S. Manual for Eysenck Personality Questionnaire. San Diego: Digits, 1975.
28. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry 1993; 50: 975-990.
29. Spielberger C. Manual for the State-Trait Anxiety Inventory. Palo Alto: Consulting Psychologists Press, 1983.
30. Carver CS, White TL. Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS Scales. J Pers Soc Psychol 1994; 67: 319-333.
31. Claridge G, Broks P. Schizotypy and hemisphere function.-I: Theoretical considerations and the measurement of schizotypy. Pers Individ Dif 1984; 5: 633-648.
32. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263-265.
33. Dudbridge F. Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 2003; 25: 115-121.
34. Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics 2000; 155: 945-959.
35. Markon KE. Modeling psychopathology structure: a symptom-level analysis of Axis I and II disorders. Psychol Med 2010; 40: 273-288.
36. Mendlowicz MV, Jean-Louis G, Kelsoe JR, Akiskal HS. A comparison of recovered bipolar patients, healthy relatives of bipolar probands, and normal controls using the short TEMPS-A. J Affect Disord 2005; 85: 147-151.
37. Miklowitz DJ, Johnson SL. Social and familial factors in the course of bipolar disorder: basic processes and relevant interventions. Clin Psychol 2009; 16: 281-296.
38. Bijl RV, van Zessen G, Ravelli A. Psychiatric morbidity among adults in The Netherlands: the NEMESIS-Study. II. Prevalence of psychiatric disorders. Netherlands Mental Health Survey and Incidence Study. Ned Tijdschr Geneeskd 1997; 141: 2453-2460.
39. Brown TA, Barlow DH. Comorbidity among anxiety disorders: implications for treatment and DSM-IV. J Consult Clin Psychol 1992; 60: 835-844.
40. Pirkola SP, Isometsä E, Suvisaari J et al. DSM-IV mood-, anxiety- and alcohol use disorders and their comorbidity in the Finnish general population--results from the Health 2000 Study. Soc Psychiatry Psychiatr Epidemiol 2005; 40: 1-10.
41. van Balkom AJ, Beekman AT, de Beurs E, Deeg DJ, van Dyck R, van Tilburg W. Comorbidity of the anxiety disorders in a community-based older population in The Netherlands. Acta Psychiatr Scand 2000; 101: 37-45.
42. Fava M, Rankin MA, Wright EC et al. Anxiety disorders in major depression. Compr Psychiatry 2000; 41: 97-102.
43. Hazlett H, Dawson ME, Schell AM, Nuechterlein KH. Electrodermal activity as a prodromal sign in schizophrenia. Biol Psychiatry 1997; 41: 111-113.
44. Sariusz-Skapska M, Czabala C, Dudek D, Zieba A, Rduch S. Personality traits in patients with unipolar and bipolar disorder. Psychiatr Pol 2003; 37: 225-233.
45. Smillie LD, Bhairo Y, Gray J et al. Personality and the bipolar spectrum: normative and classification data for the Eysenck Personality Questionnaire-Revised. Compr Psychiatry 2009; 50: 48-53.
46. Van Os J, Jones PB. Neuroticism as a risk factor for schizophrenia. Psychol Med 2001; 31: 1129-1134.
47. Costa PT Jr, McCrae RR. Influence of extraversion and neuroticism on subjective well-being: happy and unhappy people. J Pers Soc Psychol 1980; 38: 668-678.
48. Larsen RJ, Ketelaar T. Personality and susceptibility to positive and negative emotional states. J Pers Soc Psychol 1991; 61: 132-140.
49. Watson D, Clark L, Carey G. Positive and negative affectivity and their relation to anxiety and depressive disorders. J Abnorm Psychol 1998; 97: 346-353.
50. Cloninger CR. A systematic method for clinical description and classification of personality variants. A proposal. Arch Gen Psychiatry 1987; 44: 573-588.
51. Fowles DC. Psychophysiology and psychopathology: a motivational approach. Psychophysiology 1988; 25: 373-391.
52. Mineka S, Watson D, Clark LA. Comorbidity of anxiety and unipolar mood disorders. Annu Rev Psychol 1998; 49: 377-412.
53. Kasch KL, Rottenberg J, Arnow BA, Gotlib IH. Behavioral activation and inhibition systems and the severity and course of depression. J Abnorm Psychol 2002; 111: 589-597.
54. Carlson GA, Goodwin FK. The stages of mania. A longitudinal analysis of the manic episode. Arch Gen Psychiatry 1973; 28: 221-228.
55. Akiskal HS, Hantouche EG, Bourgeois ML et al. Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN). J Affect Disord 1998; 50: 175-186.
56. Cassidy F, Murry E, Forest K, Carroll BJ. Signs and symptoms of mania in pure and mixed episodes. J Affect Disord 1998; 50: 187-201.
57. Bauer MS, Whybrow PC, Gyulai L, Gonnel J, Yeh HS. Testing definitions of dysphoric mania and hypomania: prevalence, clinical characteristics and inter-episode stability. J Affect Disord 1994; 32: 201-211.
58. McElroy SL, Strakowski SM, Keck PE Jr, Tugrul KL, West SA, Lonczak HS. Differences and similarities in mixed and pure mania. Compr Psychiatry 1995; 36: 187-194.
59. Benazzi F, Akiskal HS. Delineating bipolar II mixed states in the Ravenna-San Diego collaborative study: the relative prevalence and diagnostic significance of hypomanic features during major depressive episodes. J Affect Disord 2001; 67: 115-122.
60. Perugi G, Akiskal HS, Ramacciotti S et al. Depressive comorbidity of panic, social phobic, and obsessive-compulsive disorders re-examined: is there a bipolar II connection? J Psychiatr Res 1999; 33: 53-61.
61. Lish JD, Dime-Meenan S, Whybrow PC, Price RA, Hirschfeld RM. The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord 1994; 31: 281-294.
62. Egeland JA, Hostetter AM, Pauls DL, Sussex JN. Prodromal symptoms before onset of manic-depressive disorder suggested by first hospital admission histories. J Am Acad Child Adolesc Psychiatry 2000; 39: 1245-1252.
63. Egeland JA, Shaw JA, Endicott J et al. Prospective study of prodromal features for bipolarity in well Amish children. J Am Acad Child Adolesc Psychiatry 2003; 42: 786-796.
64. Haro G, Calabrese JR, Larsson C et al. The relationship of personality traits to substance abuse in patients with bipolar disorder. Eur Psychiatry 2007; 22: 305-308.
65. Nery FG, Hatch JP, Glahn DC et al. Temperament and character traits in patients with bipolar disorder and associations with comorbid alcoholism or anxiety disorders. J Psychiatr Res 2008; 42: 569-577.
66. Olvera RL, Fonseca M, Caetano SC et al. Assessment of personality dimensions in children and adolescents with bipolar disorder using the Junior Temperament and Character Inventory. J Child Adolesc Psychopharmacol 2009; 19: 13-21.
67. Tillman R, Geller B, Craney JL et al. Temperament and character factors in a prepubertal and early adolescent bipolar disorder phenotype compared to attention deficit hyperactive and normal controls. J Child Adolesc Psychopharmacol 2003; 13: 531-543.
68. Young LT, Bagby RM, Cooke RG, Parker JD, Levitt AJ, Joffe RT. A comparison of Tridimensional Personality Questionnaire dimensions in bipolar disorder and unipolar depression. Psychiatry Res 1995; 58: 139-143.
69. Chatterjee S, Sunitha TA, Velayudhan A, Khanna S. An investigation into the psychobiology of social phobia: personality domains and serotonergic function. Acta Psychiatr Scand 1997; 95: 544-550.
70. Mörtberg E, Bejerot S, Aberg Wistedt A. Temperament and character dimensions in patients with social phobia: patterns of change following treatments? Psychiatry Res 2007; 152: 81-90.
71. Schneier FR, Blanco C, Antia SX, Liebowitz MR. The social anxiety spectrum. Psychiatr Clin North Am 2002; 25: 757-774.
72. Perugi G, Akiskal HS, Toni C, Simonini E, Gemignani A. The temporal relationship between anxiety disorders and (hypo)mania: a retrospective examination of 63 panic, social phobic and obsessive-compulsive patients with comorbid bipolar disorder. J Affect Disord 2001; 67: 199-206.
73. Arts B, Jabben N, Krabbendam L, van Os J. Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychol Med 2008; 38: 771-785.
74. Bora E, Yucel M, Pantelis C. Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord 2009; 113: 1-20.
75. Bast T, Feldon J. Hippocampal modulation of sensorimotor processes. Prog Neurobiol 2003; 70: 319-345.
76. Macedo CE, Angst MJ, Guiberteau T, Brasse D, O'Brien TJ, Sandner G. Acoustic hypersensitivity in adult rats after neonatal ventral hippocampus lesions. Behav Brain Res 2010; 207: 161-168.
77. Angst MJ, Macedo CE, Guiberteau T, Sandner G. Alteration of conditioned emotional response and conditioned taste aversion after neonatal ventral hippocampus lesions in rats. Brain Res 2007; 1143: 183-192.
78. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 2000; 23: 155-184.
79. Hahn T, Dresler T, Plichta MM et al. Functional amygdala-hippocampus connectivity during anticipation of aversive events is associated with Gray's trait "sensitivity to punishment". Biol Psychiatry 2010; 68: 459-464.
80. Oler JA, Fox AS, Shelton SE et al. Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature 2010; 466: 864-868.
81. McEwen BS. Effects of adverse experiences for brain structure and function. Biol Psychiatry 2000; 48: 721-731.
82. McLaughlin KJ, Baran SE, Conrad CD. Chronic stress- and sex-specific neuromorphological and functional changes in limbic structures. Mol Neurobiol 2009; 40: 166-182.
83. Haldane M, Frangou S. New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 943-960.
84. Strakowski SM, DelBello MP, Sax KW et al. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999; 56: 254-260.
85. Frodl T, Meisenzahl E, Zetzsche T et al. Enlargement of the amygdala in patients with a first episode of major depression. Biol Psychiatry 2002; 51: 708-714.
86. Ramel W, Goldin PR, Eyler LT, Brown GG, Gotlib IH, McQuaid JR. Amygdala reactivity and mood-congruent memory in individuals at risk for depressive relapse. Biol Psychiatry 2007; 61: 231-239.
87. Lange C, Irle E. Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med 2004; 34: 1059-1064.
88. Davis M. Neural systems involved in fear-potentiated startle. Ann N Y Acad Sci 1989; 563: 165-183.
89. Wessa M, Linke J, Witt SH et al. The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol Psychiatry 2010; 15: 1126-1127.
90. de Kloet ER, Joëls M, Holsboer F. Stress and the brain: from adaptation to disease. Nat Rev Neurosci 2005; 6: 463-475.
91. Willour VL, Chen H, Toolan J et al. Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry 2009; 14: 261-268.
92. Pezawas L, Meyer-Lindenberg A, Drabant EM et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 2005; 8: 828-834.
93. McGorry PD, Hickie IB, Yung AR, Pantelis C, Jackson HJ. Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry 2006; 40: 616-622.
94. McGorry PD, Killackey E, Yung A. Early intervention in psychosis: concepts, evidence and future directions. World Psychiatry 2008; 7: 148-156.
95. Insel TR. Translating scientific opportunity into public health impact: a strategic plan for research on mental illness. Arch Gen Psychiatry 2009; 66: 128-133.
96. McGorry PD. Risk syndromes, clinical staging and DSM V: new diagnostic infrastructure for early intervention in psychiatry. Schizophr Res 2010; 120: 49-53.
97. Berk M, Hallam KT, McGorry PD. The potential utility of a staging model as a course specifier: a bipolar disorder perspective. J Affect Disord 2007; 100: 279-281.
98. Eaton WW, Badawi M, Melton B. Prodromes and precursors: epidemiologic data for primary prevention of disorders with slow onset. Am J Psychiatry 1995; 152: 967-972.
99. Harrington R, Clark A. Prevention and early intervention for depression in adolescence and early adult life. Eur Arch Psychiatry Clin Neurosci 1998; 248: 32-45.
100. Yung AR, Phillips LJ, Yuen HP, McGorry PD. Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophr Res 2004; 67: 131-142.
101. Hetrick SE, Parker AG, Hickie IB, Purcell R, Yung AR, McGorry PD. Early identification and intervention in depressive disorders: towards a clinical staging model. Psychother Psychosom 2008; 77: 263-270.
102. Seeley JR, Stice E, Rohde P. Screening for depression prevention: identifying adolescent girls at high risk for future depression. J Abnorm Psychol 2009; 118: 161-170.