title: Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls.
abstract: BACKGROUND
  There is a decreased serotonergic function in impulsive aggression and borderline personality disorder (BPD), and genetic association studies suggest a role of serotonergic genes in impulsive aggression and BPD. Only one study has analyzed the association between the tryptophan-hydroxylase 2 (TPH2) gene and BPD. A TPH2 "risk" haplotype has been described that is associated with anxiety, depression and suicidal behavior.
  
  
  METHODS
  We assessed the relationship between the previously identified "risk" haplotype at the TPH2 locus and BPD diagnosis, impulsive aggression, affective lability, and suicidal/parasuicidal behaviors, in a well-characterized clinical sample of 103 healthy controls (HCs) and 251 patients with personality disorders (109 with BPD). A logistic regression including measures of depression, affective lability and aggression scores in predicting "risk" haplotype was conducted.
  
  
  RESULTS
  The prevalence of the "risk" haplotype was significantly higher in patients with BPD compared to HCs. Those with the "risk" haplotype have higher aggression and affect lability scores and more suicidal/parasuicidal behaviors than those without it. In the logistic regression model, affect lability was the only significant predictor and it correctly classified 83.1% of the subjects as "risk" or "non-risk" haplotype carriers.
  
  
  CONCLUSIONS
  We found an association between the previously described TPH2 "risk" haplotype and BPD diagnosis, affective lability, suicidal/parasuicidal behavior, and aggression scores.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, Psychiatry Box # 1230, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: M Mercedes
authors.initials: MM
authors.lastname: Perez-Rodriguez
authors.forename: Shauna
authors.initials: S
authors.lastname: Weinstein
authors.forename: Antonia S
authors.initials: AS
authors.lastname: New
authors.forename: Laura
authors.initials: L
authors.lastname: Bevilacqua
authors.forename: Qiaoping
authors.initials: Q
authors.lastname: Yuan
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Zhou
authors.forename: Colin
authors.initials: C
authors.lastname: Hodgkinson
authors.forename: Marianne
authors.initials: M
authors.lastname: Goodman
authors.forename: Harold W
authors.initials: HW
authors.lastname: Koenigsberg
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
mesh_terms: D000328:Adult; D000374:Aggression / Q000523:psychology*; D001883:Borderline Personality Disorder / Q000208:ethnology / Q000235:genetics* / Q000523:psychology*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012737:Sex Factors; D013406:Suicide, Attempted / Q000523:psychology; D011795:Surveys and Questionnaires; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D044465:White People / Q000208:ethnology
chemical_list: C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase
references.citation: Am J Psychiatry. 1997 Oct;154(10):1430-5
references.pmid: 9326827
references.citation: J Consult Psychol. 1957 Aug;21(4):343-9
references.pmid: 13463189
references.citation: Arch Gen Psychiatry. 1994 Jan;51(1):20-7
references.pmid: 7506515
references.citation: Alcohol Alcohol. 2008 Sep-Oct;43(5):505-15
references.pmid: 18477577
references.citation: Arch Gen Psychiatry. 1989 Jul;46(7):613-6
references.pmid: 2472125
references.citation: Acta Psychiatr Scand. 2000 May;101(5):395-402
references.pmid: 10823300
references.citation: Psychiatry Res. 2004 Apr 15;126(1):23-32
references.pmid: 15081624
references.citation: Arch Gen Psychiatry. 1961 Jun;4:561-71
references.pmid: 13688369
references.citation: Genet Epidemiol. 2004 Dec;27(4):321-33
references.pmid: 15368617
references.citation: J Pers Disord. 2001 Feb;15(1):33-40
references.pmid: 11236813
references.citation: Mol Psychiatry. 2005 Oct;10(10):944-9
references.pmid: 15940290
references.citation: Arch Gen Psychiatry. 2005 Oct;62(10):1109-18
references.pmid: 16203956
references.citation: Psychiatry Res. 2004 Jan 1;121(3):239-52
references.pmid: 14675743
references.citation: Am J Psychiatry. 2002 Dec;159(12):2048-54
references.pmid: 12450955
references.citation: Genes Brain Behav. 2005 Nov;4(8):482-5
references.pmid: 16268992
references.citation: Biochem Pharmacol. 2003 Nov 1;66(9):1673-80
references.pmid: 14563478
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Feb 1;33(1):128-33
references.pmid: 19032968
references.citation: J Psychiatr Res. 2004 May-Jun;38(3):223-30
references.pmid: 15003426
references.citation: CNS Spectr. 2003 Oct;8(10):737-54
references.pmid: 14712172
references.citation: Int J Neuropsychopharmacol. 2006 Aug;9(4):437-42
references.pmid: 16146581
references.citation: Am J Psychiatry. 2000 Apr;157(4):609-14
references.pmid: 10739421
references.citation: Pharmacogenomics J. 2003;3(2):101-4
references.pmid: 12746735
references.citation: Arch Gen Psychiatry. 1982 Jul;39(7):795-9
references.pmid: 7165479
references.citation: Compr Psychiatry. 2000 Nov-Dec;41(6):416-25
references.pmid: 11086146
references.citation: Behav Brain Funct. 2008 Oct 20;4:48
references.pmid: 18937842
references.citation: J Psychiatr Res. 2006 Aug;40(5):448-53
references.pmid: 16690085
references.citation: J Neuropsychiatry Clin Neurosci. 1991 Spring;3(2):S52-6
references.pmid: 1687961
references.citation: Psychiatr Genet. 2007 Jun;17(3):153-7
references.pmid: 17417058
references.citation: Zhonghua Liu Xing Bing Xue Za Zhi. 2006 Feb;27(2):137-41
references.pmid: 16749995
references.citation: Biol Psychiatry. 2002 Jun 15;51(12):951-63
references.pmid: 12062878
references.citation: Neuropsychopharmacology. 2002 May;26(5):660-71
references.pmid: 11927191
references.citation: Br J Psychiatry. 1992 May;160:643-6
references.pmid: 1591573
references.citation: Psychiatry Res. 1997 Nov 14;73(1-2):1-14
references.pmid: 9463834
references.citation: Neuropsychopharmacology. 2006 Sep;31(9):1982-90
references.pmid: 16495936
references.citation: Am J Psychiatry. 2001 May;158(5):775-82
references.pmid: 11329401
references.citation: Psychiatry Res. 2005 Apr 15;134(2):195-8
references.pmid: 15840421
references.citation: Neuropsychopharmacology. 2007 Jul;32(7):1629-40
references.pmid: 17203018
references.citation: Mol Psychiatry. 2005 Dec;10(12):1126-32
references.pmid: 16116490
references.citation: Am J Med Genet. 1998 Feb 7;81(1):13-7
references.pmid: 9514581
references.citation: Psychiatry Res. 2003 Aug 1;119(3):205-16
references.pmid: 12914892
references.citation: Psychopharmacol Bull. 1990;26(3):393-405
references.pmid: 2274641
references.citation: Biol Psychiatry. 1996 Aug 1;40(3):157-64
references.pmid: 8830948
references.citation: J Clin Psychol. 1989 Sep;45(5):786-93
references.pmid: 2808736
references.citation: Child Abuse Negl. 2003 Feb;27(2):169-90
references.pmid: 12615092
references.citation: Psychopharmacology (Berl). 2004 Nov;176(3-4):451-8
references.pmid: 15160265
references.citation: J Pers Soc Psychol. 1992 Sep;63(3):452-9
references.pmid: 1403624
references.citation: J Clin Psychopharmacol. 1991 Apr;11(2):116-20
references.pmid: 2056138
references.citation: J Clin Psychopharmacol. 1990 Oct;10(5):373-5
references.pmid: 2258454
references.citation: Biol Psychiatry. 2007 Jul 1;62(1):72-80
references.pmid: 17217922
references.citation: Mol Psychiatry. 2004 Oct;9(10):896-7
references.pmid: 15197398
references.citation: Am J Psychiatry. 1991 Oct;148(10):1378-85
references.pmid: 1897620
references.citation: Arch Gen Psychiatry. 2008 Dec;65(12):1438-46
references.pmid: 19047531
references.citation: Psychiatry Res. 1988 May;24(2):187-94
references.pmid: 2457227
references.citation: Mol Psychiatry. 2004 Nov;9(11):1030-6
references.pmid: 15124006
references.citation: Psychiatry Res. 1996 Mar 29;60(2-3):177-84
references.pmid: 8723308
references.citation: Biol Psychiatry. 2004 Oct 15;56(8):581-6
references.pmid: 15476687
references.citation: Am J Psychiatry. 2008 Apr;165(4):429-42
references.pmid: 18346997
references.citation: Psychiatr Genet. 2007 Dec;17(6):339-43
references.pmid: 18075474
references.citation: Int J Eat Disord. 2005 Jan;37(1):57-60
references.pmid: 15690467
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(5):663-74
references.pmid: 1981394
references.citation: Psychoneuroendocrinology. 2003 May;28(4):559-73
references.pmid: 12689612
references.citation: Int Clin Psychopharmacol. 1995 Sep;10(3):177-9
references.pmid: 8675971
references.citation: Am J Psychiatry. 2005 May;162(5):883-9
references.pmid: 15863789
references.citation: Psychiatr Clin North Am. 2008 Sep;31(3):441-61, vii
references.pmid: 18638645
references.citation: J Psychiatr Pract. 2002 May;8(3):133-42
references.pmid: 15985870
references.citation: Neurosci Lett. 2006 Nov 20;408(3):214-9
references.pmid: 17000047
references.citation: Biol Psychiatry. 2002 Jun 15;51(12):964-8
references.pmid: 12062879
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2005 May 5;135B(1):42-6
references.pmid: 15768392
references.citation: Arch Gen Psychiatry. 1989 Jul;46(7):587-99
references.pmid: 2735812
references.citation: Am J Psychiatry. 2006 Jan;163(1):20-6
references.pmid: 16390884
references.citation: Arch Gen Psychiatry. 1978 Jul;35(7):837-44
references.pmid: 678037
references.citation: Ann N Y Acad Sci. 2004 Dec;1032:104-16
references.pmid: 15677398
references.citation: Psychiatr Clin North Am. 2000 Mar;23(1):27-40, vi
references.pmid: 10729929
references.citation: Harv Rev Psychiatry. 2003 Jan-Feb;11(1):8-19
references.pmid: 12866737