Genetics of impulsive behaviour

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 368, Issue 1615, 2013, Pages

  Bevilacqua, Laura ^a   Goldman, David ^b  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM   (United States)

Author keywords

Genes; Heritability; HTR2B; Impulsivity; Sequencing

Indexed keywords

ALLELE; ETIOLOGY; FUNCTIONAL ROLE; GENE EXPRESSION; GENOME; HERITABILITY; HUMAN BEHAVIOR; MENTAL HEALTH; NEUROLOGY; PHENOTYPE; PSYCHOLOGY; RODENT;

AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; AMINE OXIDASE (FLAVIN CONTAINING); MONOAMINE OXIDASE A, HUMAN; SEROTONIN; SEROTONIN 2B RECEPTOR;

ALLELE; ANIMAL; ATTENTION; COGNITION; DRUG EFFECT; ENZYMOLOGY; GENETIC HETEROGENEITY; GENETICS; GENOTYPE; HIGH RISK BEHAVIOR; HUMAN; IMPULSIVENESS; INHERITANCE; KNOCKOUT MOUSE; METABOLISM; MOUSE; REVIEW; STOP CODON;

ALLELES; ANIMALS; ATTENTION; CODON, TERMINATOR; COGNITION; GENETIC HETEROGENEITY; GENOTYPE; HUMANS; IMPULSIVE BEHAVIOR; INHERITANCE PATTERNS; MICE; MICE, KNOCKOUT; MONOAMINE OXIDASE; NEUROTRANSMITTER AGENTS; RECEPTOR, SEROTONIN, 5-HT2B; RISK-TAKING; SEROTONIN;

EID: 84883885513     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2012.0380     Document Type: Review

References (146)

1. Evenden JL. 1999 Varieties of impulsivity. Psychopharmacology (Berl.) 146, 348-361.(doi:10.1007/PL00005481)
2. Dalley JW, Everitt BJ, Robbins TW. 2011 Impulsivity, compulsivity and top-down cognitive control. Neuron 69, 680-694.(doi:10.1016/j.neuron.2011.01.020)
3. Winstanley CA. 2011 The utility of rat models of impulsivity in developing pharmacotherapies for impulse control disorders. Br. J. Pharmacol. 164,1301-1321.(doi:10.1111/j.1476-5381.2011.01323.x)
4. Bickel WK, Odum AL, Madden GJ. 1999 Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers. Psychopharmacology (Berl.) 146, 447-454.(doi:10.1007/PL00005490)
5. Reynolds B, Leraas K, Collins C, Melanko S. 2009 Delay discounting by children of smokers and nonsmokers. Drug Alcohol Depend. 99, 350-353.(doi:10.1016/j.drugalcdep.2008.07.015)
6. Anokhin AP, Golosheykin S, Grant JD, Heath AC. 2011 Heritability of delay discounting in adolescence: a longitudinal twin study. Behav. Genet. 41, 175-183.(doi:10.1007/s10519-010-9384-7)
7. Reynolds B, Schiffbauer R. 2004 Measuring state changes in human delay discounting: an experiential discounting task. Behav. Process. 67, 343-356.
8. Schweitzer JB, Sulzer-Azaroff B. 1995 Self-control in boys with attention deficit hyperactivity disorder: effects of added stimulation and time. J. Child Psychol. Psychiat. Appl. Disciplines 36, 671-686.
9. Kirby KN, Petri NM. 2004 Heroin and cocaine abusers have higher discount rates for delayed rewards than alcoholics or non-drug-using controls. Addiction 99, 461-471.(doi:10.1111/j.1360-0443.2003.00669.x)
10. de Wit H, Flory JD, Acheson A, McCloskey M, Manuch SB. 2007 IQ and nonplanning impulsivity are independently associated with delay discounting in middle-aged adults. Pers. Individual Differ. 42, 111-121.(doi:10.1016/j.paid.2006.06.026)
11. Barratt ES. 1965 Factor analysis of some psychometric measures of impulsiveness and anxiety. Psychol. Rep. 16, 547-554.(doi:10.2466/pr0.1965.16.2.547)
12. de Wit H. 2009 Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict. Biol. 14, 22-31.(doi:10.1111/j.1369-1600.2008.00129.x)
13. Perry JL, Carroll ME. 2008 The role of impulsive behavior in drug abuse. Psychopharmacology (Berl.) 200, 1-26.(doi:10.1007/s00213-008-1173-0)
14. Verdejo-Garcia A, Lawrence AJ, Clark L. 2008 Impulsivity as a vulnerability marker for substanceuse disorders: review of findings from high-risk research, problem gamblers and genetic association studies. Neurosci. Biobehav. Rev. 32, 777-810.(doi:10.1016/j.neubiorev.2007.11.003)
15. Cardinal RN, Pennicott DR, Sugathapala CL, Robbins TW, Everitt BJ. 2001 Impulsive choice induced in rats by lesions of the nucleus accumbens core. Science 292, 2499-2501.(doi:10.1126/science.1060818)
16. Winstanley CA, Theobald DE, Dalley JW, Cardinal RN, Robbins TW. 2006 Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice. Cereb. Cortex 16, 106-114.(doi:10.1093/cercor/bhi088)
17. Kable JW, Glimcher PW. 2009 The neurobiology of decision: consensus and controversy. Neuron 63, 733-745.(doi:10.1016/j.neuron.2009.09.003)
18. Hariri AR, Brown SM, Williamson DE, Flory JD, de Wit H, Manuck SB. 2006 Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity. J. Neurosci. 26, 13213-13217.(doi:10.1523/JNEUROSCI.3446-06.2006)
19. Lejuez CW, Read JP, Kahler CW, Richards JB, Ramsey SE, Stuart GL, Strong DR, Brown RA. 2002 Evaluation of a behavioral measure of risk-taking: The Balloon Analogue Risk Task (BART). J. Exp. Psychol. 8, 75-84.
20. Bechara A, Damasio AR, Damasio H, Anderson SW. 1994 Insensitivity to frontal cortex following damage to human prefrontal cortex. Cognition 50, 7-15.(doi:10.1016/0010-0277(94)90018-3)
21. Hopko DR, Lejuez CW, Daughters SB, Aklin WM, Osborne A, Simmons BL, Strong DR. 2006 Construct validity of the Balloon Analogue Risk Task (BART): relationship with MDMA use by inner-city drug users in residential treatment. J. Psychopathol. Behav. Assess. 28, 95-101.(doi:10.1007/s10862-006-7487-5)
22. Bornovalova MA, Cashman-Rolls A, O'Donnell JMM, Ettinger K, Richards JB, de Wit H, Lejuez CW. 2009 Risk taking differences on a behavioral task as a function of potential reward/loss magnitude and individual differences in impulsivity and sensation seeking. Pharmacol. Biochem. Behav. 93, 258-262.(doi:10.1016/j.pbb.2008.10.023)
23. Eysenck HJ, Eysenck SBG. 1985 Personality and individual differences: a natural science approach. New York, NY: Plenum Press.
24. Hunt MK, Hopko DR, Bare R, Lejuez CW, Robinson EV. 2005 Construct validity of the Balloon Analog Risk Task (BART): associations with psychopathy and impulsivity. Assessment 12, 416-428.(doi:10.1177/1073191105278740)
25. Bechara A. 2004 The role of emotion in decisionmaking: evidence from neurological patients with orbitofrontal damage. Brain Cognition 55, 30-40.(doi:10.1016/j.bandc.2003.04.001)
26. Li X, Lu ZL, D'Argembeau A, Ng M, Bechara A. 2010 The Iowa Gambling Task in fMRI images. Hum. Brain Mapp. 31, 410-423.
27. Rao H, Korczykowski M, Pluta J, Hoang A, Detre JA. 2008 Neural correlates of voluntary and involuntary risk taking in the human brain: an fMRI study of the Balloon Analog Risk Task (BART). Neuro Image 42, 902-910.(doi:10.1016/j.neuroimage. 2008.05.046)
28. Zeeb FD, Robbins TW, Winstanley CA. 2009 Serotonergic and dopaminergic modulation of gambling behavior as assessed using a novel rat gambling task. Neuropsychopharmacology 34, 2329-2343.(doi:10.1038/npp.2009.62)
29. Logan GD. 1994 On the ability to inhibit thought and action. A user's guide to the stop signal paradigm. In Inhibitory processes in attention, memory and language (eds D Dagenbach, TH Carr), pp. 189-239. San Diego, CA: Academic Press.
30. Logan GD, Schachar RJ, Tannock R. 1997 Impulsivity and inhibitory control. Psychol. Sci. 8, 60-64.(doi:10.1111/j.1467-9280.1997.tb00545.x)
31. Tannock R, Schachar RJ, Carr RP, Chajczyk D, Logan GD. 1989 Effects of methylphenidate on inhibitory control in hyperactive children. J. Abnorm. Child Psychol. 17, 473-491.(doi:10.1007/BF00916508)
32. Newman JP, Widom CS, Nathan S. 1985 Passive avoidance in syndromes of disinhibition: psychopathology and extraversion. J. Pers. Soc. Psychol. 48, 1316-1327.(doi:10.1037/0022-3514.48.5.1316)
33. Dom G, De Wilde B, Hulstijn W, van den Brink W, Sabbe B. 2006 Behavioural aspects of impulsivity in alcoholics with and without a cluster-B personality disorder. Alcohol Alcohol. 41, 412-420.(doi:10.1093/alcalc/agl030)
34. Horn NR, Dolan M, Elliott R, Deakin JF, Woodruff PW. 2003 Response inhibition and impulsivity: an fMRI study. Neuropsychologia 41, 1959-1966.(doi:10.1016/S0028-3932(03)00077-0)
35. Reynolds B, Ortengren A, Richards JB, de Wit H. 2006 Dimensions of impulsive behavior: personality and behavioral measures. Pers. Individual Differ. 40, 305-315.(doi:10.1016/j.paid.2005.03.024)
36. Cheung AM, Mitsis EM, Halperin JM. 2004 The relationship of behavioral inhibition to executive function in young adults. J. Clin. Exp. Neuropsychol. 26, 393-404.(doi:10.1080/13803390490510103)
37. Berlin L, Bohlin G. 2002 Response inhibition, hyperactivity, and conduct problems among preschool children. J. Clin. Child Adolesc. Psychol. 31, 242-251.
38. Casey BJ et al. 2007 Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD. Am. J. Psychiat. 164, 1729-1736.(doi:10.1176/appi.ajp.2007.06101754)
39. Aron AR. 2010 From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses. Biol. Psychiat. 69, e55-e68.(doi:10.1016/j.biopsych.2010.07.024)
40. Dodds CM, Morein-Zamir S, Robbins TW. 2010 Dissociating inhibition, attention, and response control in the frontoparietal network using functional magnetic resonance imaging. Cereb. Cortex 21, 1155-1165.(doi:10.1093/cercor/bhq187)
41. Robbins TW. 2002 The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl.) 163, 362-380.(doi:10.1007/s00213-002-1154-7)
42. Rosvold HE, Mirsky A, Sarason L, Bransome Jr ED, Beck LH. 1956 A continuous performance test of brain damage. J. Consult. Psychol. 20, 334-350.(doi:10.1037/h0043220)
43. Krishnan-Sarin S, Reynolds B, Duhig AM, Smith A, Liss T, McFetridge A, Cavallo DA, Carroll KM, Potenza MN. 2007 Behavioral impulsivity predicts treatment outcome in a smoking cessation program for adolescent smokers. Drug Alcohol Depend. 88, 79-82.(doi:10.1016/j.drugalcdep.2006.09.006)
44. Swann AC, Bjork JM, Moeller FG, Doughetry DM. 2002 Two models of impulsivity: relationship to personality traits and psychopathology. Biol. Psychiat. 51, 988-994.(doi:10.1016/S0006-3223(01)01357-9)
45. Epstein JN, Erkanli A, Conners CK, Klaric J, Costello JE, Angold A. 2003 Relations between continuous performance test performance measures and ADHD behaviors. J. Abnorm. Child Psychol. 31, 543-554.(doi:10.1023/A:1025405216339)
46. Murphy ER, Robinson ES, Theobald DE, Dalley JW, Robbins TW. 2008 Contrasting effects of selective lesions of nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behaviour. Eur. J. Neurosci. 28, 353-363.(doi:10.1111/j.1460-9568.2008.06309.x)
47. Stanford MS, Mathias CW, Dougherty DM, Lake SL, Anderson NE, Patton JH. 2009 Fifty years of the Barratt Impulsiveness Scale: an update and review. Pers. Individual Differ. 47, 385-395.(doi:10.1016/j.paid.2009.04.008)
48. Whiteside SP, Lynam DR. 2001 The Five Factor Model and impulsivity: using a structural model of personality to understand impulsivity. Pers. Individual Differ. 30, 669-689.(doi:10.1016/S0191-8869(00)00064-7)
49. Lecrubier Y, Braconnier A, Said S, Payan C. 1995 The impulsivity rating scale (IRS): preliminary results. Eur. Psychiat. 10, 331-338.(doi:10.1016/0924-9338(96)80333-6)
50. Gustavsson JP. 2000 Swedish universities Scales of Personality (SSP): construction, internal consistency and normative data. Acta Psychiat. Scand. 102, 217-225.(doi:10.1034/j.1600-0447.2000. 102003217.x)
51. Cloninger CR, Przybeck TR, Svrakic DM. 1991 The tridimensional personality questionnaire: U.S. normative data. Psychol. Rep. 69, 1047-1057.
52. Tellegen A, Waller NG. 1994 Exploring personality through test construction: development of the multidimensional personality questionnaire. Greenwich, CT: JAI Press.
53. Buss AH, Durkee A. 1957 An inventory for assessing different kinds of hostility. J. Consult. Psychol. 21, 343-349.(doi:10.1037/h0046900)
54. Asahi S, Okamoto Y, Okada G, Yamawaki S, Yokota N. 2004 Negative correlation between right prefrontal activity during response inhibition and impulsiveness: a fMRI study. Eur. Arch. Psychiat. Clin. Neurosci. 254, 245-251.(doi:10.1007/s00406-004-0488-z)
55. Brown SM, Manuck SB, Flory JD, Hariri AR. 2006 Neural basis of individual differences in impulsivity: contributions of corticolimbic circuits for behavioral arousal and control. Emotion 6, 239-245.(doi:10.1037/1528-3542.6.2.239)
56. Sripada CS, Gonzalez R, Phan KL, Liberzon I. 2011 The neural correlates of intertemporal decisionmaking: contributions of subjective value, stimulus type, and trait impulsivity. Hum. Brain Mapp. 32, 1637-1648.(doi:10.1002/hbm.21136)
57. de Quervain DJ, Fischbacher U, Treyer V, Schellhammer M, Schnyder U, Buck A, Fehr E. 2004 The neural basis of altruistic punishment. Science 305, 1254-1258.(doi:10.1126/science.1100735)
58. Moll J, Krueger F, Zahn R, Pardini M, de Oliveira-Souza R, Grafman J. 2006 Human fronto-mesolimbic networks guide decisions about charitable donation. Proc. Natl Acad. Sci. USA 103, 15623-15628.(doi:10.1073/pnas.0604475103)
59. Lee B et al. 2009 Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. J. Neurosci. 29, 14734-14740.(doi:10.1523/JNEUROSCI.3765-09.2009)
60. Nelson RJ, Trainor BC. 2007 Neural mechanisms of aggression. Nature 8, 536-546.(doi:10.1038/nrn2174)
61. Seroczynski AD, Bergeman CS, Coccaro EF. 1999 Etiology of the impulsivity/aggression relationship: genes or environment? Psychiat. Res. 86, 41-57.(doi:10.1016/S0165-1781(99)00013-X)
62. Kendler KS, Aggen SH, Czajkowski N, Røysamb E, Tambs K, Torgersen S, Neale MC, Reichborn-Kjennerud T. 2008 The structure of genetic and environmental risk factors for DSMIV personality disorders: a multivariate twin study. Arch. Gen. Psychiat. 65, 1438-1446.(doi:10.1001/archpsyc.65.12.1438)
63. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF. 1979 Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychol.Res. 1, 131-139.
64. Virkkunen M et al. 1994 CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch. Gen. Psychiat. 51, 20-27.(doi:10.1001/archpsyc.1994.03950010020003)
65. Sjoberg RL, Ducci F, Barr CS, Newman TK, Dell'osso L, Virkkunen M, Goldman D. 2008 A non-additive interaction of a functional MAO-A VNTR and testosterone predicts antisocial behavior. Neuropsychopharmacology 33, 425-430.(doi:10.1038/sj.npp.1301417)
66. Bevilacqua L, Carli V, Sarchiapone M, George DK, Goldman D, Roy A, Enoch MA. 2012 Interaction between FKBP5 and childhood trauma increases risk for aggressive behavior. Arch. Gen. Psychiat. 69, 62-70.(doi:10.1001/archgenpsychiatry.2011.152)
67. Coccaro EF, Bergeman CS, McClearn GE. 1993 Heritability of irritable impulsiveness: a study of twins reared together and apart. Psychiat. Res. 48, 229-242.(doi:10.1016/0165-1781(93)90074-Q)
68. Hicks BM, Krueger RF, Iacono WG, McGue M, Patrick CJ. 2004 Family transmission and heritability of externalizing disorders. Arch. Gen. Psychiat. 61, 922-928.(doi:10.1001/archpsyc.61.9.922)
69. Hur YM, Bouchard Jr TJ. 1997 The genetic correlation between impulsivity and sensation seeking traits. Behav. Genet. 27, 455-463.(doi:10.1023/A:1025674417078)
70. Pedersen NL, Plomin R, McClearn GE, Friberg L. 1988 Neuroticism, extraversion, and related traits in adult twins reared apart and reared together. J. Pers. Soc. Psychol. 55, 950-957.(doi:10.1037/ 0022-3514.55.6.950)
71. Keller MC, Coventry WL, Heath AC, Martin NG. 2005 Widespread evidence for non-additive genetic variation in Cloninger's and Eysenck's personality dimensions using a twin plus sibling design. Behav. Genetics 35, 707-721.(doi:10.1007/s10519-005-6041-7)
72. Zietsch BP, Verweij KJH, Bailey JM, Wright MJ, Martin NG. 2010 Genetic and environmental influences on risky sexual behavior and its relationship with personality. Behav. Genetics 40, 12-21.(doi:10.1007/s10519-009-9300-1)
73. Ersche KD, Turton AJ, Pradhan S, Bullmore ET, Robbins TW. 2010 Drug addiction endophenotypes: impulsive versus sensation-seeking personality traits. Biol. Psychiat. 68, 770-773.(doi:10.1016/j. biopsych.2010.06.015)
74. Anokhin AP, Golosheykin S, Grant J, Heath AC. 2009 Heritability of risk-taking in adolescence: a longitudinal twin study. Twin Res. Hum. Genet. 12, 366-371.(doi:10.1375/twin.12.4.366)
75. Higley JD, Thompson WW, Champoux M, Goldman D, Hasert MF, Kraemer GW, Scanlan JM, Suomi SJ, Linnoila M. 1993 Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in rhesus monkeys (Macaca mulatta). Arch. Gen. Psychiat. 50, 615-623.(doi:10. 1001/archpsyc.1993.01820200025003)
76. Limson R, Goldman D, Roy A, Lamparski D, Ravitz B, Adinoff B, Linnoila M. 1991 Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls. Arch. Gen. Psychiat. 48, 437-441.(doi:10.1001/archpsyc.1991.01810290049010)
77. Bevilacqua L et al. 2010 A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature 468, 1061-1066.(doi:10.1038/nature09629)
78. Juhasz G et al. 2010 Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders. Neuropsychopharmacology 35,1109-1119.(doi:10.1038/npp.2009.216)
79. Jollant F, Buresi C, Guillaume S, Jaussent I, Bellivier F, Leboyer M, Castelnau D, Malafosse A, Courtet P. 2007 The influence of four serotonin-related genes on decision-making in suicide attempters. Am. J. Med. Genet. B Neuropsychiat. Genet. 144B, 615-624.(doi:10.1002/ajmg.b.30467)
80. Stoltenberg SF, Glass JM, Chermack ST, Flynn HA, Li S, Weston ME, Burmeister M. 2006 Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene. Psychiat. Genet. 16, 35-38.(doi:10.1097/01.ypg.0000176528.30362.34)
81. Walderhaug E, Herman AI, Magnusson A, Morgan MJ, Landrø NI. 2010 The short (S) allele of the serotonin transporter polymorphism and acute tryptophan depletion both increase impulsivity in me. Nneurosci. Lett. 473, 208-211.(doi:10.1016/j.neulet.2010.02.048)
82. Roiser JP, Rogers RD, Cook LJ, Sahakian BJ. 2006 The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controls. Psychopharmacology (Berl.) 188, 213-227.(doi:10.1007/s00213-006-0495-z)
83. Lage GM, Malloy-Diniz LF, Matos LO, Bastos MA, Abrantes SS, Correéa H. 2011 Impulsivity and the 5-HTTLPR polymorphism in a non-clinical sample. PLoS ONE 6, e16927.(doi:10.1371/journal.pone.0016927)
84. Sonuga-Barke EJ et al. 2011 A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings. Biol. Psychiat. 70, 230-236.(doi:10.1016/j.biopsych.2011.01.040)
85. Cummins TD, Hawi Z, Hocking J, Strudwick M, Hester R, Garavan H, Wagner J, Chambers CD, Bellgrove MA. 2011 Dopamine transporter genotype predicts behavioural and neural measures of response inhibition. Mol. Psychiat. 17, 1086-1092.(doi:10.1038/mp.2011.104)
86. Paloyelis Y, Asherson P, Mehta MA, Faraone SV, Kuntsi J. 2010 DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls. Neuropsychopharmacology 35, 2414-2426. (doi:10.1038/npp.2010.124)
87. Chiavegatto S, Dawson VL, Mamounas LA, Koliatsos VE, Dawson TM, Nelson RJ. 2001 Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nictric oxide synthase. Proc. Natl Acad. Sci. USA 98, 1277-1281.(doi:10.1073/pnas.98.3.1277)
88. Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK. 1983 Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci. 33, 2609-2614.(doi:10.1016/0024-3205(83)90344-2)
89. Virkkunen M, Linnoila M. 1993 Brain serotonin, type II alcoholism and impulsive violence. J. Stud. Alcohol Suppl. 11, 163-169.
90. Miczek KA, de Almeida RM. 2001 Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT1B agonist anpirtoline. Psychopharmacology (Berl.) 157, 421-429.(doi:10.1007/s002130100831)
91. Zhou Z, Roy A, Lipsky R, Kuchipudi K, Zhu G, Taubman J, Enoch MA, Virkkunen M, Goldman D. 2005 Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Arch. Gen. Psychiat. 62, 1109-1118.(doi:10.1001/archpsyc.62.10.1109)
92. Brunner HG, Nelen M, Breakefield XO, Ropers HH, vanOost BA. 1993 Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262, 578-580.(doi:10.1126/science.8211186)
93. Cases O, Lebrand C, Giros B, Vitalis T, De Maeyer E, Caron MG, Price DJ, Gaspar P, Seif I. 1998 Plasma membrane transporters of serotonin, dopamine, and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs. J. Neurosci. 18, 6914-6927.
94. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R. 2002 Role of genotype in the cycle of violence in maltreated children. Science 297, 851-854.(doi:10.1126/science.1072290)
95. Ducci FMA, Hodgkinson C, Xu K, Catena M, Robin RW, Goldman D. 2007 Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women. Mol. Psychiat. 13, 334-347.(doi:10.1038/sj.mp.4002034)
96. Parsey RV, Oquendo MA, Simpson NR, Ogden RT, Van Heertum R, Arango V, Mann JJ. 2002 Effects of sex, age, and aggressive traits in man on brain serotonin 5-HT1A receptor binding potential measured by PET using [C-11]WAY-100635. Brain Res. 954, 173-182.(doi:10.1016/S0006-8993(02)03243-2)
97. Benko A et al. 2010 Significant association between the C(-1019)G functional polymorphism of the HTR1A gene and impulsivity. Am. J. Med. Genet. B Neuropsychiat.Genet. 153B, 592-599.(doi:10.1002/ajmg.b.31025)
98. Crabbe JC, Phillips TJ, Feller DJ, Hen R, Wenger CD, Lessov CN, Schafer GL. 1996 Elevated alcohol consumption in null mutant mice lacking 5-HT1B serotonin receptors. Nat. Genet. 14, 98-101.(doi:10.1038/ng0996-98)
99. Soyka M, Preuss UW, Koller G, Zill P, Bondy B. 2004 Association of 5-HT1B receptor gene and antisocial behavior and alcoholism. J. Neural. Transm. 111, 101-109.(doi:10.1007/s00702-003-0064-0)
100. Lappalainen J et al. 1998 Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch. Gen. Psychiat. 55, 989-994.(doi:10.1001/archpsyc.55.11.989)
101. Talpos JC, Wilkinson LS, Robbins TW. 2006 A comparison of multiple 5-HT receptors in two tasks measuring impulsivity. J. Psychopharmacol. 20, 47-58.(doi:10.1177/0269881105056639)
102. Ducci F, Enoch MA, Yuan Q, Shen PH, White KV, Hodgkinson C, Albaugh B, Virkkunen M, Goldman D. 2009 HTR3B is associated with alcoholism, with antisocial behavior and alpha EEG power-an intermediate phenotype for alcoholism and comorbid behaviors. Alcohol 43, 73-84.(doi:10.1016/j.alcohol.2008.09.005)
103. Hu XZ et al. 2006 Serotonin transporter promoter gain-of-function genotypes are linked to obsessivecompulsive disorder. Am. J. Hum. Genet. 78, 815-826.(doi:10.1086/503850)
104. Caspi A et al. 2003 Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386-389.(doi:10.1126/science.1083968)
105. Roy A, Hu XZ, Janal MN, Goldman D. 2007 Interaction between childhood trauma and serotonin transporter gene variation in suicide. Neuropsychopharmacology 32, 2046-2052.(doi:10.1038/sj.npp.1301331)
106. Sakado K, Sakado M, Muratake T, Mundt C, Someya T. 2003 A psychometrically derived impulsive trait related to a polymorphism in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in a Japanese nonclinical population: assessment by the Barratt impulsiveness scale (BIS). Am. J. Med. Genet. B Neuropsychiat. Genet. 121B, 71-75.(doi:10.1002/ajmg.b.20063)
107. Everitt BJ, Belin D, Economidou D, Pelloux Y, Dalley JW, Robbins TW. 2008 Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Phil. Trans. R. Soc. B 363, 3125-3135.(doi:10.1098/rstb.2008.0089)
108. Faraone SV, Mick E. 2005 Molecular genetics of attention deficit hyperactivity disorder. Psychiat. Clin. North Am. 33, 159-180.(doi:10.1016/j.psc.2009.12.004)
109. Aron AR, Dowson JH, Sahakian BJ, Robbins TW. 2003 Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder. Biol. Psychiat. 54, 1465-1468.(doi:10.1016/S0006-3223(03)00609-7)
110. Nandam LS et al. 2011 Methylphenidate but not atomoxetine or citalopram modulates inhibitory control and response time variability. Biol. Psychiat. 69, 902-904.(doi:10.1016/j.biopsych.2010.11.014)
111. Neale BM et al. 2010 Case-control genome-wide association study of attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiat. 49, 906-920.(doi:10.1016/j.jaac.2010.06.007)
112. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. 2001 Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl Acad. Sci. USA 98, 6917-6922.(doi:10.1073/pnas.111134598)
113. Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D. 2003 COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science 299, 1240-1243.(doi:10.1126/science.1078546)
114. Diatchenko L et al. 2005 Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum. Mol. Genet. 14, 135-143.(doi:10.1093/hmg/ddi013)
115. Goldman D, Orszi G, Ducci F. 2005 The genetics of addictions: uncovering the genes. Nat. Rev. Genet. 6, 521-532.(doi:10.1038/nrg1635)
116. Cirulli ET, Goldstein DB. 2010 Uncovering the roles of rare variants in common disease through wholegenome sequencing. Nature 11, 415-425.(doi:10.1038/nrg2779)
117. Maher B. 2008 Personal genomes: the case of the missing heritability. Nature 456, 18-21.(doi:10.1038/456018a)
118. Manolio TA et al. 2009 Finding the missing heritability of complex diseases. Nature 461, 747-753.(doi:10.1038/nature08494)
119. Schork NJ, Murray SS, Frazer KA, Topol EJ. 2009 Common vs rare allele hypotheses for complex disease. Curr. Opin. Genet. Dev. 19, 212-219.(doi:10.1016/j.gde.2009.04.010)
120. Gudbjartsson DF et al. 2008 Many sequence variants affecting diversity of adult human height. Nat. Genet. 40, 609-615.(doi:10.1038/ng.122)
121. Zeggini E et al. 2008 Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638-645.(doi:10.1038/ng.120)
122. Verweij KJ et al. 2010 A genome-wide association study of Cloninger's temperament scales: implications for the evolutionary genetics of personality. Biol. Psychol. 85, 306-317.(doi:10.1016/j.biopsycho.2010.07.018)
123. McCrae RR, Costa Jr PT. 2003 Personality in adulthood: a five factor theory perspective. New York, NY: Guilford Press.
124. Terracciano A et al. 2010 Genome-wide association scan for five major dimensions of personality. Mol. Psychiat. 15, 647-656.(doi:10.1038/mp.2008.113)
125. Goldman D. 2010 Gene x environment interactions in complex behavior: first, build a telescope. Biol. Psychiat. 67, 295-296.(doi:10.1016/j.biopsych.2009.12.005)
126. Hodgkinson CA et al. 2010 Genome-wide association identifies candidate genes that influence the human electroencephalogram. Proc. Natl Acad. Sci. USA 107, 8695-8700.(doi:10.1073/pnas.0908134107)
127. Yang J et al. 2010 Common SNPs explain a large proportion of the heritability for human height. Nat. Genet. 47, 565-569.(doi:10.1038/ng.608)
128. Kong A et al. 2009 Parental origin of sequence variants associated with complex diseases. Nature 462, 868-874.(doi:10.1038/nature08625)
129. Bobadilla JL, Macek Jr M, Finem JP, Farrellm PM. 2002 Cystic fibrosis: a worldwide analysis of CFTRmutations-correlation with incidence data and application to screening. Hum. Mutat. 19, 575-606.(doi:10.1002/humu.10041)
130. Szabo C, Masiello A, Ryan JF, Brody LC. 2000 The breast cancer information core: database design, structure, and scope. Hum. Mutat. 16, 123-131.(doi:10.1002/1098-1004(200008)16:2,123::AIDHUMU4.3.0. CO;2-Y)
131. Ng SB et al. 2009 Targeted capture and massivelyparallel sequencing of 12 human exomes. Nature 461, 272-276.(doi:10.1038/nature08250)
132. Ng SB et al. 2010 Exome sequencing identifies the cause of a Mendelian disorder. Nat. Genet. 42, 30-35.(doi:10.1038/ng.499)
133. O'Roak BJ et al. 2011 Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat. Genet. 43, 585-589.(doi:10.1038/ng.835)
134. Vissers LE et al. 2010 A de novo paradigm for mental retardation. Nat. Genet. 42, 1109-1112.(doi:10.1038/ng.712)
135. Peltonen L, Jalanko A, Varilo T. 1999 Molecular genetics of the Finnish disease heritage. Hum. Mol. Genet. 8, 1913-1923.(doi:10.1093/hmg/8.10.1913)
136. Baxter GS, Murphy OE, Blackburn TP. 1994 Further characterization of 5-hydroxytryptamine receptors (putative 5-HT2B) in rat stomach fundus longitudinal muscle. Br. J. Pharmacol. 112, 323-333.(doi:10.1111/j.1476-5381.1994.tb13072.x)
137. Bonaventure P et al. 2002 Nuclei and subnuclei gene expression profiling in mammalian brain. Brain Res. 943, 38-47.(doi:10.1016/S0006-8993(02)02504-0)
138. Choi DS, Maroteaux L. 1996 Immunohistochemical localisation of the serotonin 5-HT2B receptor in mouse gut, cardiovascular system, and brain. FEBS Lett. 391, 45-51.(doi:10.1016/0014-5793(96)00695-3)
139. Doly S, Valjent E, Setola V, Callebert J, Hervé D, Launay JM, Maroteaux L. 2008 Serotonin 5-HT2B receptors are required for 3,4-methylenedi oxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro. J. Neurosci. 28, 2933-2940.(doi:10.1523/JNEUROSCI.5723-07.2008)
140. Kennett GA, Trail B, Bright F. 1998 Anxiolytic-like actions of BW 723C86 in the rat Vogel conflict test are 5-HT2B receptor mediated. Neuropharmacology 37, 1603-1610.(doi:10.1016/S0028- 3908(98)00115-4)
141. Yadav VK et al. 2009 A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138, 976-989.(doi:10.1016/j.cell.2009.06.051)
142. Launay JM, Schneider B, Loric S, Da Prada M, Kellermann O. 2006 Serotonin transport and serotonin transporter-mediated antidepressant recognition are controlled by 5-HT2B receptor signaling in serotonergic neuronal cells. FASEB J. 20, 1843-1854.(doi:10.1096/fj.06-5724com)
143. Hayes DJ, Greenshaw AJ. 2011 5-HT receptors and reward-related behaviour: a review. Neurosci. Biobehav. Rev. 35, 1419-1449.(doi:10.1016/j.neubiorev.2011.03.005)
144. Rothman RB, Baumann MH. 2006 Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs. Ann. NY Acad. Sci. 1074, 245-260.(doi:10.1196/annals.1369.064)
145. Doly S et al. 2009 Role of serotonin via 5-HT2B receptors in the reinforcing effects of MDMA in mice. PLoS ONE 4, e7952.(doi:10.1371/journal. pone.0007952)
146. Auclair AL, Cathala A, Depoortere R, Piazza PV, Newman-Tancredi A, Spampinato U. 2010 The central serotonin 2B receptor: a new pharmacological target to modulate the mesoaccumbens dopaminergic pathway activity. J. Neurochem. 114, 1323-1332.