Advertisement

Journal of Applied Genetics

, Volume 53, Issue 4, pp 389–413 | Cite as

Endophenotypes as a measure of suicidality

  • Dimitry A. ChistiakovEmail author
  • Zurab I. Kekelidze
  • Vladimir P. Chekhonin
Human Genetics • Review

Abstract

Suicide is thought to result from the harmful interaction of multiple factors that have social, environmental, neurobiological, and genetic backgrounds. Recent studies have suggested that genetic predisposition to suicidal behavior may be independent of the risk of suicide associated to mental disorders, such as affective disorders, schizophrenia, or alcohol dependence. Given the suicidal behavior heterogeneity and its hereditary complexity, the need to find demonstrable intermediate phenotypes that may make it possible to establish links between genes and suicide behaviors (endophenotypes) seems to be necessary. The main objective of this review was to consider the candidate endophenotypes of suicidal behaviors. Due to the recent advances in neuroimaging, we also characterize brain regions implicated in vulnerability to suicide behavior that are influenced by gene polymorphisms associated with suicidal behavior.

Keywords

Suicidal behavior Endophenotype Major depression Serotonergic system Genetic polymorphism Association 

References

  1. Albert PR, Le François B, Millar AM (2011) Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Mol Brain 4:21PubMedGoogle Scholar
  2. Alexander N, Osinsky R, Schmitz A, Mueller E, Kuepper Y, Hennig J (2010) The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress. Psychoneuroendocrinology 35:949–953PubMedGoogle Scholar
  3. Anguelova M, Benkelfat C, Turecki G (2003) A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Mol Psychiatry 8:574–591PubMedGoogle Scholar
  4. Anisman H, Grimmer L, Irwin J, Remington G, Sklar LS (1979) Escape performance after inescapable shock in selectively bred lines of mice: response maintenance and catecholamine activity. J Comp Physiol Psychol 93:229–241PubMedGoogle Scholar
  5. Arango V, Underwood MD, Gubbi AV, Mann JJ (1995) Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res 688:121–133PubMedGoogle Scholar
  6. Arango V, Underwood MD, Mann JJ (2002) Serotonin brain circuits involved in major depression and suicide. Prog Brain Res 136:443–453PubMedGoogle Scholar
  7. Arango V, Huang YY, Underwood MD, Mann JJ (2003) Genetics of the serotonergic system in suicidal behavior. J Psychiatr Res 37:375–386PubMedGoogle Scholar
  8. Armbruster D, Mueller A, Moser DA, Lesch KP, Brocke B, Kirschbaum C (2009) Interaction effect of D4 dopamine receptor gene and serotonin transporter promoter polymorphism on the cortisol stress response. Behav Neurosci 123:1288–1295PubMedGoogle Scholar
  9. Armbruster D, Mueller A, Strobel A, Lesch KP, Brocke B, Kirschbaum C (2011a) Predicting cortisol stress responses in older individuals: influence of serotonin receptor 1A gene (HTR1A) and stressful life events. Horm Behav 60:105–111PubMedGoogle Scholar
  10. Armbruster D, Mueller A, Strobel A, Lesch KP, Brocke B, Kirschbaum C (2011b) Children under stress—COMT genotype and stressful life events predict cortisol increase in an acute social stress paradigm. Int J Neuropsychopharmacol 12:1–11Google Scholar
  11. Asberg M (1997) Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies. Ann N Y Acad Sci 836:158–181PubMedGoogle Scholar
  12. Asberg M, Nordström P, Träskman-Bendz L (1986) Cerebrospinal fluid studies in suicide. An overview. Ann N Y Acad Sci 487:243–255PubMedGoogle Scholar
  13. Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65:1157–1165PubMedGoogle Scholar
  14. Audenaert K, Van Laere K, Dumont F, Slegers G, Mertens J, van Heeringen C, Dierckx RA (2001) Decreased frontal serotonin 5-HT 2a receptor binding index in deliberate self-harm patients. Eur J Nucl Med 28:175–182PubMedGoogle Scholar
  15. Bach-Mizrachi H, Underwood MD, Tin A, Ellis SP, Mann JJ, Arango V (2008) Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides. Mol Psychiatry 13:507–513PubMedGoogle Scholar
  16. Bäckman CM, Shan L, Zhang YJ, Hoffer BJ, Leonard S, Troncoso JC, Vonsatel P, Tomac AC (2006) Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson’s disease: a real-time PCR study. Mol Cel Endocrinol 252:160–166Google Scholar
  17. Baldessarini RJ, Tondo L, Hennen J (2003) Lithium treatment and suicide risk in major affective disorders: update and new findings. J Clin Psychiatry 64:44–52PubMedGoogle Scholar
  18. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837PubMedGoogle Scholar
  19. Bartels M, Van den Berg M, Sluyter F, Boomsma DI, de Geus EJ (2003) Heritability of cortisol levels: review and simultaneous analysis of twin studies. Psychoneuroendocrinology 28:121–137PubMedGoogle Scholar
  20. Bechara A, Damasio AR, Damasio H, Anderson SW (1994) Insensitivity to future consequences following damage to human prefrontal cortex. Cognition 50:7–15PubMedGoogle Scholar
  21. Bellivier F, Chaste P, Malafosse A (2004) Association between the TPH gene A218C polymorphism and suicidal behavior: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet 124B:87–91PubMedGoogle Scholar
  22. Benko A, Lazary J, Molnar E, Gonda X, Tothfalusi L, Pap D, Mirnics Z, Kurimay T, Chase D, Juhasz G, Anderson IM, Deakin JF, Bagdy G (2010) Significant association between the C(−1019)G functional polymorphism of the HTR1A gene and impulsivity. Am J Med Genet B Neuropsychiatr Genet 153B:592–599PubMedGoogle Scholar
  23. Bertolino A, Arciero G, Rubino V, Latorre V, De Candia M, Mazzola V, Blasi G, Caforio G, Hariri A, Kolachana B, Nardini M, Weinberger DR, Scarabino T (2005) Variation of human amygdala response during threatening stimuli as a function of 5′HTTLPR genotype and personality style. Biol Psychiatry 57:1517–1525PubMedGoogle Scholar
  24. Blanchard RJ, Wall PM, Blanchard DC (2003) Problems in the study of rodent aggression. Horm Behav 44:161–170PubMedGoogle Scholar
  25. Boldrini M, Underwood MD, Mann JJ, Arango V (2005) More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides. Brain Res 1041:19–28PubMedGoogle Scholar
  26. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L (1998) Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 95:9608–9613PubMedGoogle Scholar
  27. Bondy B, Erfurth A, de Jonge S, Krüger M, Meyer H (2000) Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide. Mol Psychiatry 5(2):193–195PubMedGoogle Scholar
  28. Bondy B, Buettner A, Zill P (2006) Genetics of suicide. Mol Psychiatry 11:336–351PubMedGoogle Scholar
  29. Bonkale WL, Murdock S, Janosky JE, Austin MC (2004) Normal levels of tryptophan hydroxylase immunoreactivity in the dorsal raphe of depressed suicide victims. J Neurochem 88:958–964PubMedGoogle Scholar
  30. Bonkale WL, Turecki G, Austin MC (2006) Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressed suicide subjects is restricted to the dorsal subnucleus. Synapse 60:81–85PubMedGoogle Scholar
  31. Bornovalova MA, Hicks BM, Iacono WG, McGue M (2009) Stability, change, and heritability of borderline personality disorder traits from adolescence to adulthood: a longitudinal twin study. Dev Psychopathol 21:1335–1353PubMedGoogle Scholar
  32. Brent DA, Oquendo M, Birmaher B, Greenhill L, Kolko D, Stanley B, Zelazny J, Brodsky B, Firinciogullari S, Ellis SP, Mann JJ (2003) Peripubertal suicide attempts in offspring of suicide attempters with siblings concordant for suicidal behavior. Am J Psychiatry 160:1486–1493PubMedGoogle Scholar
  33. Brezo J, Paris J, Tremblay R, Vitaro F, Zoccolillo M, Hébert M, Turecki G (2006) Personality traits as correlates of suicide attempts and suicidal ideation in young adults. Psychol Med 36:191–202PubMedGoogle Scholar
  34. Brezo J, Klempan T, Turecki G (2008) The genetics of suicide: a critical review of molecular studies. Psychiatr Clin North Am 31:179–203PubMedGoogle Scholar
  35. Bridge JA, McBee-Strayer SM, Cannon EA, Sheftall AH, Reynolds B, Campo JV, Pajer KA, Barbe RP, Brent DA (2012) Impaired decision making in adolescent suicide attempters. J Am Acad Child Adolesc Psychiatry 51:394–403PubMedGoogle Scholar
  36. Brodsky BS, Stanley B (2008) Adverse childhood experiences and suicidal behavior. Psychiatr Clin North Am 31:223–235PubMedGoogle Scholar
  37. Brown SM, Peet E, Manuck SB, Williamson DE, Dahl RE, Ferrell RE, Hariri AR (2005) A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Mol Psychiatry 10:884–888PubMedGoogle Scholar
  38. Butler AW, Breen G, Tozzi F, Craddock N, Gill M, Korszun A, Maier W, Middleton LT, Mors O, Owen MJ, Perry J, Preisig M, Rice JP, Rietschel M, Jones L, Farmer AE, Lewis CM, McGuffin P (2010) A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12. Am J Med Genet B Neuropsychiatr Genet 153B:1465–1473PubMedGoogle Scholar
  39. Calati R, Porcelli S, Giegling I, Hartmann AM, Möller HJ, De Ronchi D, Serretti A, Rujescu D (2011) Catechol-o-methyltransferase gene modulation on suicidal behavior and personality traits: review, meta-analysis and association study. J Psychiatr Res 45:309–321PubMedGoogle Scholar
  40. Canli T, Congdon E, Gutknecht L, Constable RT, Lesch KP (2005) Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation. J Neural Transm 112:1479–1485PubMedGoogle Scholar
  41. Caspi A, Moffitt TE, Newman DL, Silva PA (1996) Behavioral observations at age 3 years predict adult psychiatric disorders. Longitudinal evidence from a birth cohort. Arch Gen Psychiatry 53:1033–1039PubMedGoogle Scholar
  42. Cerasa A, Gioia MC, Labate A, Lanza P, Magariello A, Muglia M, Quattrone A (2008) MAO A VNTR polymorphism and variation in human morphology: a VBM study. Neuroreport 19:1107–1110PubMedGoogle Scholar
  43. Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24:4401–4411PubMedGoogle Scholar
  44. Cheng R, Juo SH, Loth JE, Nee J, Iossifov I, Blumenthal R, Sharpe L, Kanyas K, Lerer B, Lilliston B, Smith M, Trautman K, Gilliam TC, Endicott J, Baron M (2006) Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Mol Psychiatry 11:252–260PubMedGoogle Scholar
  45. Chong RY, Oswald L, Yang X, Uhart M, Lin PI, Wand GS (2006) The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. Neuropsychopharmacology 31:204–211PubMedGoogle Scholar
  46. Clark L, Dombrovski AY, Siegle GJ, Butters MA, Shollenberger CL, Sahakian BJ, Szanto K (2011) Impairment in risk-sensitive decision-making in older suicide attempters with depression. Psychol Aging 26:321–330PubMedGoogle Scholar
  47. Coccaro EF, Bergeman CS, Kavoussi RJ, Seroczynski AD (1997) Heritability of aggression and irritability: a twin study of the Buss–Durkee aggression scales in adult male subjects. Biol Psychiatry 41:273–284PubMedGoogle Scholar
  48. Coryell W, Schlesser M (2001) The dexamethasone suppression test and suicide prediction. Am J Psychiatry 158:748–753PubMedGoogle Scholar
  49. Courtet P, Baud P, Abbar M, Boulenger JP, Castelnau D, Mouthon D, Malafosse A, Buresi C (2001) Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene. Mol Psychiatry 6:338–341PubMedGoogle Scholar
  50. Courtet P, Jollant F, Buresi C, Castelnau D, Mouthon D, Malafosse A (2005) The monoamine oxidase A gene may influence the means used in suicide attempts. Psychiatr Genet 15:189–193PubMedGoogle Scholar
  51. Craig IW (2007) The importance of stress and genetic variation in human aggression. Bioessays 29:227–236PubMedGoogle Scholar
  52. Crawley JN (2000) What’s wrong with my mouse? Behavioral phenotyping of transgenic and knockout mice. Wiley-Liss, New YorkGoogle Scholar
  53. Crawley JN, Sutton ME, Pickar D (1985) Animal models of self-destructive behavior and suicide. Psychiatr Clin North Am 8:299–310PubMedGoogle Scholar
  54. Cremniter D, Jamain S, Kollenbach K, Alvarez JC, Lecrubier Y, Gilton A, Jullien P, Lesieur P, Bonnet F, Spreux-Varoquaux O (1999) CSF 5-HIAA levels are lower in impulsive as compared to nonimpulsive violent suicide attempters and control subjects. Biol Psychiatry 45:1572–1579PubMedGoogle Scholar
  55. Critchley HD, Elliott R, Mathias CJ, Dolan RJ (2000) Neural activity relating to generation and representation of galvanic skin conductance responses: a functional magnetic resonance imaging study. J Neurosci 20:3033–3040PubMedGoogle Scholar
  56. Cryan JF, Mombereau C (2004) In search of a depressed mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol Psychiatry 9:326–357PubMedGoogle Scholar
  57. Czesak M, Lemonde S, Peterson EA, Rogaeva A, Albert PR (2006) Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism. J Neurosci 26:1864–1871PubMedGoogle Scholar
  58. Dannlowski U, Ohrmann P, Konrad C, Domschke K, Bauer J, Kugel H, Hohoff C, Schöning S, Kersting A, Baune BT, Mortensen LS, Arolt V, Zwitserlood P, Deckert J, Heindel W, Suslow T (2009) Reduced amygdala–prefrontal coupling in major depression: association with MAOA genotype and illness severity. Int J Neuropsychopharmacol 12:11–22PubMedGoogle Scholar
  59. De Luca V, Likhodi O, Kennedy JL, Wong AH (2007) Differential expression and parent-of-origin effect of the 5-HT2A receptor gene C102T polymorphism: analysis of suicidality in schizophrenia and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 144B:370–374PubMedGoogle Scholar
  60. De Luca V, Viggiano E, Dhoot R, Kennedy JL, Wong AH (2009) Methylation and QTDT analysis of the 5-HT2A receptor 102C allele: analysis of suicidality in major psychosis. J Psychiatr Res 43:532–537PubMedGoogle Scholar
  61. DeRijk RH, Wüst S, Meijer OC, Zennaro MC, Federenko IS, Hellhammer DH, Giacchetti G, Vreugdenhil E, Zitman FG, de Kloet ER (2006) A common polymorphism in the mineralocorticoid receptor modulates stress responsiveness. J Clin Endocrinol Metab 91:5083–5089PubMedGoogle Scholar
  62. Detera-Wadleigh SD (2001) Lithium-related genetics of bipolar disorder. Ann Med 33:272–285PubMedGoogle Scholar
  63. Distel MA, Trull TJ, Derom CA, Thiery EW, Grimmer MA, Martin NG, Willemsen G, Boomsma DI (2008) Heritability of borderline personality disorder features is similar across three countries. Psychol Med 38:1219–1229PubMedGoogle Scholar
  64. Dombrovski AY, Butters MA, Reynolds CF 3rd, Houck PR, Clark L, Mazumdar S, Szanto K (2008) Cognitive performance in suicidal depressed elderly: preliminary report. Am J Geriatr Psychiatry 16(2):109–115PubMedGoogle Scholar
  65. Dorus E, Pandey GN, Frazer A, Mendels J (1974) Genetic determinant of lithium ion distribution. I. An in vitro monozygotic-dizygotic twin study. Arch Gen Psychiatry 31:463–465PubMedGoogle Scholar
  66. Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD (2002) High activity-related allele of MAO-A gene associated with depressed suicide in males. Neuroreport 13:1195–1198PubMedGoogle Scholar
  67. Dwivedi Y (2009) Brain-derived neurotrophic factor: role in depression and suicide. Neuropsychiatr Dis Treat 5:433–449PubMedGoogle Scholar
  68. Edman G, Asberg M, Levander S, Schalling D (1986) Skin conductance habituation and cerebrospinal fluid 5-hydroxyindoleacetic acid in suicidal patients. Arch Gen Psychiatry 43:586–592PubMedGoogle Scholar
  69. Einat H (2006) Modelling facets of mania—new directions related to the notion of endophenotypes. J Psychopharmacol 20:714–722PubMedGoogle Scholar
  70. Ernst C, Deleva V, Deng X, Sequeira A, Pomarenski A, Klempan T, Ernst N, Quirion R, Gratton A, Szyf M, Turecki G (2009a) Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers. Arch Gen Psychiatry 66:22–32PubMedGoogle Scholar
  71. Ernst C, Chen ES, Turecki G (2009b) Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers. Mol Psychiatry 14:830–832PubMedGoogle Scholar
  72. Escribá PV, Ozaita A, García-Sevilla JA (2004) Increased mRNA expression of alpha2A-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims. Neuropsychopharmacology 29:1512–1521PubMedGoogle Scholar
  73. Federenko IS, Nagamine M, Hellhammer DH, Wadhwa PD, Wüst S (2004) The heritability of hypothalamus pituitary adrenal axis responses to psychosocial stress is context dependent. J Clin Endocrinol Metab 89:6244–6250PubMedGoogle Scholar
  74. Fiori LM, Turecki G (2011) Epigenetic regulation of spermidine/spermine N1-acetyltransferase (SAT1) in suicide. J Psychiatr Res 45:1229–1235PubMedGoogle Scholar
  75. Flint J, Munafò MR (2008) Forum: Interactions between gene and environment. Curr Opin Psychiatry 21:315–317PubMedGoogle Scholar
  76. Friedel E, Schlagenhauf F, Sterzer P, Park SQ, Bermpohl F, Ströhle A, Stoy M, Puls I, Hägele C, Wrase J, Büchel C, Heinz A (2009) 5-HTT genotype effect on prefrontal-amygdala coupling differs between major depression and controls. Psychopharmacology (Berl) 205:261–271Google Scholar
  77. Frodl T, Schüle C, Schmitt G, Born C, Baghai T, Zill P, Bottlender R, Rupprecht R, Bondy B, Reiser M, Möller HJ, Meisenzahl EM (2007) Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch Gen Psychiatry 64:410–416PubMedGoogle Scholar
  78. Galfalvy H, Zalsman G, Huang YY, Murphy L, Rosoklija G, Dwork AJ, Haghighi F, Arango V, Mann JJ (2011) A pilot genome wide association and gene expression array study of suicide with and without major depression. World J Biol Psychiatry. doi: 10.3109/15622975.2011.597875
  79. Gaspar P, Cases O, Maroteaux L (2003) The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 4:1002–1012PubMedGoogle Scholar
  80. Gatzke-Kopp LM, Raine A, Loeber R, Stouthamer-Loeber M, Steinhauer SR (2002) Serious delinquent behavior, sensation seeking, and electrodermal arousal. J Abnorm Child Psychol 30:477–486PubMedGoogle Scholar
  81. Gilissen R, Bakermans-Kranenburg MJ, van Ijzendoorn MH, Linting M (2008) Electrodermal reactivity during the Trier Social Stress Test for children: interaction between the serotonin transporter polymorphism and children’s attachment representation. Dev Psychobiol 50:615–625PubMedGoogle Scholar
  82. Goethals I, Audenaert K, Jacobs F, Van den Eynde F, Bernagie K, Kolindou A, Vervaet M, Dierckx R, Van Heeringen C (2005) Brain perfusion SPECT in impulsivity-related personality disorders. Behav Brain Res 157:187–192PubMedGoogle Scholar
  83. Gonda X, Fountoulakis KN, Csukly G, Bagdy G, Pap D, Molnár E, Laszik A, Lazary J, Sarosi A, Faludi G, Sasvari-Szekely M, Szekely A, Rihmer Z (2011a) Interaction of 5-HTTLPR genotype and unipolar major depression in the emergence of aggressive/hostile traits. J Affect Disord 132:432–437PubMedGoogle Scholar
  84. Gonda X, Fountoulakis KN, Harro J, Pompili M, Akiskal HS, Bagdy G, Rihmer Z (2011b) The possible contributory role of the S allele of 5-HTTLPR in the emergence of suicidality. J Psychopharmacol 25:857–866PubMedGoogle Scholar
  85. Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedGoogle Scholar
  86. Gottesman II, Shields J (1972) Schizophrenia and genetics: a twin study vantage point. Academic Press, New YorkGoogle Scholar
  87. Grah M, Mihanović M, Svrdlin P, Pisk SV, Restek-Petrović B (2010) Serotonin and cortisol as suicidogenic factors in patients with PTSD. Coll Antropol 34:1433–1439PubMedGoogle Scholar
  88. Grayson DR, Jia X, Chen Y, Sharma RP, Mitchell CP, Guidotti A, Costa E (2005) Reelin promoter hypermethylation in schizophrenia. Proc Natl Acad Sci USA 102:9341–9346PubMedGoogle Scholar
  89. Guillaume S, Jollant F, Jaussent I, Lawrence N, Malafosse A, Courtet P (2009) Somatic markers and explicit knowledge are both involved in decision-making. Neuropsychologia 47:2120–2124PubMedGoogle Scholar
  90. Guo G, Ou XM, Roettger M, Shih JC (2008) The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity. Eur J Hum Genet 16:626–634PubMedGoogle Scholar
  91. Hanna GL, Himle JA, Curtis GC, Koram DQ, Veenstra-VanderWeele J, Leventhal BL, Cook EH Jr (1998) Serotonin transporter and seasonal variation in blood serotonin in families with obsessive-compulsive disorder. Neuropsychopharmacology 18:102–111PubMedGoogle Scholar
  92. Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, Egan MF, Weinberger DR (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297:400–403PubMedGoogle Scholar
  93. Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR (2005) A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62:146–152PubMedGoogle Scholar
  94. Heinz A, Smolka MN, Braus DF, Wrase J, Beck A, Flor H, Mann K, Schumann G, Büchel C, Hariri AR, Weinberger DR (2007) Serotonin transporter genotype (5-HTTLPR): effects of neutral and undefined conditions on amygdala activation. Biol Psychiatry 61:1011–1014PubMedGoogle Scholar
  95. Hesselbrock V, Dick D, Hesselbrock M, Foroud T, Schuckit M, Edenberg H, Bucholz K, Kramer J, Reich T, Goate A, Bierut L, Rice JP, Nurnberger JI Jr (2004) The search for genetic risk factors associated with suicidal behavior. Alcohol Clin Exp Res 28:70S–76SPubMedGoogle Scholar
  96. 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 Psychiatry 50:615–623PubMedGoogle Scholar
  97. Holmans P, Weissman MM, Zubenko GS, Scheftner WA, Crowe RR, Depaulo JR Jr, Knowles JA, Zubenko WN, Murphy-Eberenz K, Marta DH, Boutelle S, McInnis MG, Adams P, Gladis M, Steele J, Miller EB, Potash JB, Mackinnon DF, Levinson DF (2007) Genetics of recurrent early-onset major depression (GenRED): final genome scan report. Am J Psychiatry 164:248–258PubMedGoogle Scholar
  98. Huang YY, Battistuzzi C, Oquendo MA, Harkavy-Friedman J, Greenhill L, Zalsman G, Brodsky B, Arango V, Brent DA, Mann JJ (2004) Human 5-HT1A receptor C(−1019)G polymorphism and psychopathology. Int J Neuropsychopharmacol 7(4):441–451PubMedGoogle Scholar
  99. Huizenga NA, Koper JW, De Lange P, Pols HA, Stolk RP, Burger H, Grobbee DE, Brinkmann AO, De Jong FH, Lamberts SW (1998) A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 83(1):144–151PubMedGoogle Scholar
  100. Hung CF, Lung FW, Hung TH, Chong MY, Wu CK, Wen JK, Lin PY (2012) Monoamine oxidase A gene polymorphism and suicide: an association study and meta-analysis. J Affect Disord 136:643–649PubMedGoogle Scholar
  101. Inoue H, Yamasue H, Tochigi M, Takei K, Suga M, Abe O, Yamada H, Rogers MA, Aoki S, Sasaki T, Kasai K (2010) Effect of tryptophan hydroxylase-2 gene variants on amygdalar and hippocampal volumes. Brain Res 1331:51–57PubMedGoogle Scholar
  102. Isles AR, Humby T, Wilkinson LS (2003) Measuring impulsivity in mice using a novel operant delayed reinforcement task: effects of behavioural manipulations and d-amphetamine. Psychopharmacology (Berl) 170:376–382Google Scholar
  103. Jabbi M, Korf J, Ormel J, Kema IP, den Boer JA (2008) Investigating the molecular basis of major depressive disorder etiology: a functional convergent genetic approach. Ann N Y Acad Sci 1148:42–56PubMedGoogle Scholar
  104. Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM (1997) GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family. J Biol Chem 272:33111–33117PubMedGoogle Scholar
  105. Joensuu M, Lehto SM, Tolmunen T, Saarinen PI, Valkonen-Korhonen M, Vanninen R, Ahola P, Tiihonen J, Kuikka J, Pesonen U, Lehtonen J (2010) Serotonin-transporter-linked promoter region polymorphism and serotonin transporter binding in drug-naïve patients with major depression. Psychiatry Clin Neurosci 64:387–393PubMedGoogle Scholar
  106. Jokinen J, Nordström P (2008) HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients. Psychoneuroendocrinology 33:1387–1393PubMedGoogle Scholar
  107. Jokinen J, Nordström P (2009) HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients. J Affect Disord 116:117–120PubMedGoogle Scholar
  108. 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 Neuropsychiatr Genet 144B:615–624PubMedGoogle Scholar
  109. Jönsson EG, Norton N, Gustavsson JP, Oreland L, Owen MJ, Sedvall GC (2000) A promoter polymorphism in the monoamine oxidase A gene and its relationships to monoamine metabolite concentrations in CSF of healthy volunteers. J Psychiatric Res 34:239–244Google Scholar
  110. Kamali M, Saunders EF, Prossin AR, Brucksch CB, Harrington GJ, Langenecker SA, McInnis MG (2012) Associations between suicide attempts and elevated bedtime salivary cortisol levels in bipolar disorder. J Affect Disord 136:350–358PubMedGoogle Scholar
  111. Keilp JG, Gorlyn M, Oquendo MA, Burke AK, Mann JJ (2008) Attention deficit in depressed suicide attempters. Psychiatry Res 159:7–17PubMedGoogle Scholar
  112. Keller S, Sarchiapone M, Zarrilli F, Videtic A, Ferraro A, Carli V, Sacchetti S, Lembo F, Angiolillo A, Jovanovic N, Pisanti F, Tomaiuolo R, Monticelli A, Balazic J, Roy A, Marusic A, Cocozza S, Fusco A, Bruni CB, Castaldo G, Chiariotti L (2010) Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch Gen Psychiatry 67:258–267PubMedGoogle Scholar
  113. Kendler KS, Neale MC (2010) Endophenotype: a conceptual analysis. Mol Psychiatry 15:789–797PubMedGoogle Scholar
  114. Klempan TA, Ernst C, Deleva V, Labonte B, Turecki G (2009) Characterization of QKI gene expression, genetics, and epigenetics in suicide victims with major depressive disorder. Biol Psychiatry 66:824–831PubMedGoogle Scholar
  115. Kohli MA, Salyakina D, Pfennig A, Lucae S, Horstmann S, Menke A, Kloiber S, Hennings J, Bradley BB, Ressler KJ, Uhr M, Müller-Myhsok B, Holsboer F, Binder EB (2010) Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients. Arch Gen Psychiatry 67:348–359PubMedGoogle Scholar
  116. Kumsta R, Entringer S, Koper JW, van Rossum EF, Hellhammer DH, Wüst S (2007) Sex specific associations between common glucocorticoid receptor gene variants and hypothalamus-pituitary-adrenal axis responses to psychosocial stress. Biol Psychiatry 62:863–869PubMedGoogle Scholar
  117. Laje G, Allen AS, Akula N, Manji H, John Rush A, McMahon FJ (2009) Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients. Pharmacogenet Genomics 19(9):666–674PubMedGoogle Scholar
  118. Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, Sequeira A, Kushwaha N, Morris SJ, Basak A, Ou XM, Albert PR (2003) Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 23:8788–8799PubMedGoogle Scholar
  119. Lenzenweger MF, Pastore RE (2007) On determining sensitivity to pain in borderline personality disorder. Arch Gen Psychiatry 64:747–748PubMedGoogle Scholar
  120. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531PubMedGoogle Scholar
  121. Li D, He L (2006) Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses. Hum Genet 119:233–240PubMedGoogle Scholar
  122. Li D, He L (2007) Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Mol Psychiatry 12:47–54PubMedGoogle Scholar
  123. Li D, Duan Y, He L (2006) Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis. Biochem Biophys Res Commun 340:1006–1015PubMedGoogle Scholar
  124. Lidberg L, Tuck JR, Asberg M, Scalia-Tomba GP, Bertilsson L (1985) Homicide, suicide and CSF 5-HIAA. Acta Psychiatr Scand 71:230–236PubMedGoogle Scholar
  125. Lin PY, Tsai G (2004) Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis. Biol Psychiatry 55:1023–1030PubMedGoogle Scholar
  126. Lis E, Greenfield B, Henry M, Guilé JM, Dougherty G (2007) Neuroimaging and genetics of borderline personality disorder: a review. J Psychiatry Neurosci 32:162–173PubMedGoogle Scholar
  127. Liu X, Li H, Qin W, He G, Li D, Shen Y, Shen J, Gu N, Feng G, He L (2006) Association of TPH1 with suicidal behaviour and psychiatric disorders in the Chinese population. J Med Genet 43(2):e4PubMedGoogle Scholar
  128. Lopez de Lara C, Brezo J, Rouleau G, Lesage A, Dumont M, Alda M, Benkelfat C, Turecki G (2007) Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression. Biol Psychiatry 62:72–80PubMedGoogle Scholar
  129. Lopez VA, Detera-Wadleigh S, Cardona I; National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium, Kassem L, McMahon FJ (2007) Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts. Biol Psychiatry 61:181–186PubMedGoogle Scholar
  130. López JF, Vázquez DM, Chalmers DT, Watson SJ (1997) Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide. Ann N Y Acad Sci 836:106–134PubMedGoogle Scholar
  131. Lopez-Duran NL, Kovacs M, George CJ (2009) Hypothalamic–pituitary–adrenal axis dysregulation in depressed children and adolescents: a meta-analysis. Psychoneuroendocrinology 34:1272–1283PubMedGoogle Scholar
  132. Lothe A, Boni C, Costes N, Gorwood P, Bouvard S, Le Bars D, Lavenne F, Ryvlin P (2009) Association between triallelic polymorphism of the serotonin transporter and [18F]MPPF binding potential at 5-HT1A receptors in healthy subjects. Neuroimage 47:482–492PubMedGoogle Scholar
  133. Lothe A, Boni C, Costes N, Bouvard S, Gorwood P, Lavenne F, Alvarez M, Ryvlin P (2010) 5-HT1A gene promoter polymorphism and [18F]MPPF binding potential in healthy subjects: a PET study. Behav Brain Funct 6:37PubMedGoogle Scholar
  134. Lundberg J, Borg J, Halldin C, Farde L (2007) A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain. Psychopharmacology (Berl) 195:425–433Google Scholar
  135. Lung FW, Tzeng DS, Huang MF, Lee MB (2011) Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder. BMC Med Genet 12:74PubMedGoogle Scholar
  136. Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA (2010) Whole-genome sequencing in a patient with Charcot–Marie–Tooth neuropathy. N Engl J Med 362:1181–1191PubMedGoogle Scholar
  137. Lykken DT, Iacono WG, Haroian K, McGue M, Bouchard TJ Jr (1988) Habituation of the skin conductance response to strong stimuli: a twin study. Psychophysiology 25:4–15PubMedGoogle Scholar
  138. Lyons MJ, Eisen SA, Goldberg J, True W, Lin N, Meyer JM, Toomey R, Faraone SV, Merla-Ramos M, Tsuang MT (1998) A registry-based twin study of depression in men. Arch Gen Psychiatry 55:468–472PubMedGoogle Scholar
  139. Malone KM, Ellis SP, Currier D, John Mann J (2007) Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in depressed in-patients. Int J Neuropharmacol 10:335–343Google Scholar
  140. Mann JJ (2003) Neurobiology of suicidal behaviour. Nat Rev Neurosci 4:819–828PubMedGoogle Scholar
  141. Mann JJ, Currier DM (2010) Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression. Eur Psychiatry 25:268–271PubMedGoogle Scholar
  142. Mann JJ, Waternaux C, Haas GL, Malone KM (1999) Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry 156:181–189PubMedGoogle Scholar
  143. Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM, Dwork AJ, Arango V (2000) A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry 57:729–738PubMedGoogle Scholar
  144. Mann JJ, Bortinger J, Oquendo MA, Currier D, Li S, Brent DA (2005) Family history of suicidal behavior and mood disorders in probands with mood disorders. Am J Psychiatry 162:1672–1679PubMedGoogle Scholar
  145. Mann JJ, Currier D, Stanley B, Oquendo MA, Amsel LV, Ellis SP (2006) Can biological tests assist prediction of suicide in mood disorders? Int J Neuropsychopharmacol 9:465–474PubMedGoogle Scholar
  146. Mann JJ, Arango VA, Avenevoli S, Brent DA, Champagne FA, Clayton P, Currier D, Dougherty DM, Haghighi F, Hodge SE, Kleinman J, Lehner T, McMahon F, Mościcki EK, Oquendo MA, Pandey GN, Pearson J, Stanley B, Terwilliger J, Wenzel A (2009) Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry 65:556–563PubMedGoogle Scholar
  147. Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF (2000) A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res 95:9–23PubMedGoogle Scholar
  148. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, Fulton LA, Locke DP, Magrini VJ, Abbott RM, Vickery TL, Reed JS, Robinson JS, Wylie T, Smith SM, Carmichael L, Eldred JM, Harris CC, Walker J, Peck JB, Du F, Dukes AF, Sanderson GE, Brummett AM, Clark E, McMichael JF, Meyer RJ, Schindler JK, Pohl CS, Wallis JW, Shi X, Lin L, Schmidt H, Tang Y, Haipek C, Wiechert ME, Ivy JV, Kalicki J, Elliott G, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson MA, Baty J, Heath S, Shannon WD, Nagarajan R, Link DC, Walter MJ, Graubert TA, DiPersio JF, Wilson RK, Ley TJ (2009) Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 361:1058–1066PubMedGoogle Scholar
  149. Markett S, Montag C, Walter NT, Plieger T, Reuter M (2011) On the molecular genetics of flexibility: the case of task-switching, inhibitory control and genetic variants. Cogn Affect Behav Neurosci 11:644–651PubMedGoogle Scholar
  150. Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998) Rodent data and general hypothesis: antipsychotic action exerted through 5-Ht2A receptor antagonism is dependent on increased serotonergic tone. J Neural Transm 105:365–396PubMedGoogle Scholar
  151. McGee R, Williams S, Nada-Raja S (2001) Low self-esteem and hopelessness in childhood and suicidal ideation in early adulthood. J Abnorm Child Psychol 29:281–291PubMedGoogle Scholar
  152. McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Meaney MJ, Turecki G, Szyf M (2008) Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One 3:e2085PubMedGoogle Scholar
  153. McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348PubMedGoogle Scholar
  154. Mejia JM, Ervin FR, Baker GB, Palmour RM (2002) Monoamine oxidase inhibition during brain development induces pathological aggressive behavior in mice. Biol Psychiatry 52:811–821PubMedGoogle Scholar
  155. Melhem NM, Brent DA, Ziegler M, Iyengar S, Kolko D, Oquendo M, Birmaher B, Burke A, Zelazny J, Stanley B, Mann JJ (2007) Familial pathways to early-onset suicidal behavior: familial and individual antecedents of suicidal behavior. Am J Psychiatry 164:1364–1370PubMedGoogle Scholar
  156. Mendlewicz J, Verbanck P, Linkowski P, Wilmotte J (1978) Lithium accumulation in erythrocytes of manic-depressive patients: an in vivo twin study. Br J Psychiatry 133:436–444PubMedGoogle Scholar
  157. Mestek A, Hurley JH, Bye LS, Campbell AD, Chen Y, Tian M, Liu J, Schulman H, Yu L (1995) The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C. J Neurosci 15:2396–2406PubMedGoogle Scholar
  158. Meyer TD, Hautzinger M (2003) The structure of affective symptoms in a sample of young adults. Compr Psychiatry 44:110–116PubMedGoogle Scholar
  159. Meyer RE, Salzman C, Youngstrom EA, Clayton PJ, Goodwin FK, Mann JJ, Alphs LD, Broich K, Goodman WK, Greden JF, Meltzer HY, Normand SL, Posner K, Shaffer D, Oquendo MA, Stanley B, Trivedi MH, Turecki G, Beasley CM Jr, Beautrais AL, Bridge JA, Brown GK, Revicki DA, Ryan ND, Sheehan DV (2010) Suicidality and risk of suicide—definition, drug safety concerns, and a necessary target for drug development: a consensus statement. J Clin Psychiatry 71:e1–e21PubMedGoogle Scholar
  160. Mueller A, Armbruster D, Moser DA, Canli T, Lesch KP, Brocke B, Kirschbaum C (2011) Interaction of serotonin transporter gene-linked polymorphic region and stressful life events predicts cortisol stress response. Neuropsychopharmacology 36:1332–1339PubMedGoogle Scholar
  161. Mueller A, Strahler J, Armbruster D, Lesch KP, Brocke B, Kirschbaum C (2012) Genetic contributions to acute autonomic stress responsiveness in children. Int J Psychophysiol 83:302–308PubMedGoogle Scholar
  162. Murphy TM, Ryan M, Foster T, Kelly C, McClelland R, O’Grady J, Corcoran E, Brady J, Reilly M, Jeffers A, Brown K, Maher A, Bannan N, Casement A, Lynch D, Bolger S, Tewari P, Buckley A, Quinlivan L, Daly L, Kelleher C, Malone KM (2011) Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms. Behav Brain Funct 7:22PubMedGoogle Scholar
  163. Neves FS, Malloy-Diniz LF, Romano-Silva MA, Aguiar GC, de Matos LO, Correa H (2010) Is the serotonin transporter polymorphism (5-HTTLPR) a potential marker for suicidal behavior in bipolar disorder patients? J Affect Disord 125:98–102PubMedGoogle Scholar
  164. Nierenberg AA, Alpert JE, Gaynes BN, Warden D, Wisniewski SR, Biggs MM, Trivedi MH, Barkin JL, Rush AJ (2008) Family history of completed suicide and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study. J Affect Disord 108:129–134PubMedGoogle Scholar
  165. Nordström P, Samuelsson M, Asberg M, Träskman-Bendz L, Aberg-Wistedt A, Nordin C, Bertilsson L (1994) CSF 5-HIAA predicts suicide risk after attempted suicide. Suicide Life Threat Behav 24:1–9PubMedGoogle Scholar
  166. Ono H, Shirakawa O, Kitamura N, Hashimoto T, Nishiguchi N, Nishimura A, Nushida H, Ueno Y, Maeda K (2002) Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls. Mol Psychiatry 7:1127–1132PubMedGoogle Scholar
  167. Oquendo MA, Placidi GP, Malone KM, Campbell C, Keilp J, Brodsky B, Kegeles LS, Cooper TB, Parsey RV, van Heertum RL, Mann JJ (2003) Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression. Arch Gen Psychiatry 60:14–22PubMedGoogle Scholar
  168. Oquendo MA, Galfalvy H, Russo S, Ellis SP, Grunebaum MF, Burke A, Mann JJ (2004) Prospective study of clinical predictors of suicidal acts after a major depressive episode in patients with major depressive disorder or bipolar disorder. Am J Psychiatry 161:1433–1441PubMedGoogle Scholar
  169. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Pandey SC, Pesold C, Roberts RC, Conley RR, Tamminga CA (2002) Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiatry 159:419–429PubMedGoogle Scholar
  170. Pattij T, Vanderschuren LJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29:192–199PubMedGoogle Scholar
  171. Pavlov KA, Chistiakov DA, Chekhonin VP (2012) Genetic determinants of aggression and impulsivity in humans. J Appl Genet 53:61–82PubMedGoogle Scholar
  172. Pearson TA, Manolio TA (2008) How to interpret a genome-wide association study. JAMA 299:1335–1344PubMedGoogle Scholar
  173. Perlis RH, Huang J, Purcell S, Fava M, Rush AJ, Sullivan PF, Hamilton SP, McMahon FJ, Schulze TG, Potash JB, Zandi PP, Willour VL, Penninx BW, Boomsma DI, Vogelzangs N, Middeldorp CM, Rietschel M, Nöthen M, Cichon S, Gurling H, Bass N, McQuillin A, Hamshere M; Wellcome Trust Case Control Consortium Bipolar Disorder Group, Craddock N, Sklar P, Smoller JW (2010) Genome-wide association study of suicide attempts in mood disorder patients. Am J Psychiatry 167:1499–1507PubMedGoogle Scholar
  174. Perroud N, Aitchison KJ, Uher R, Smith R, Huezo-Diaz P, Marusic A, Maier W, Mors O, Placentino A, Henigsberg N, Rietschel M, Hauser J, Souery D, Kapelski P, Bonvicini C, Zobel A, Jorgensen L, Petrovic A, Kalember P, Schulze TG, Gupta B, Gray J, Lewis CM, Farmer AE, McGuffin P, Craig I (2009) Genetic predictors of increase in suicidal ideation during antidepressant treatment in the GENDEP project. Neuropsychopharmacology 34:2517–2528PubMedGoogle Scholar
  175. Perroud N, Neidhart E, Petit B, Vessaz M, Laforge T, Relecom C, La Harpe R, Malafosse A, Guipponi M (2010) Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims. Am J Med Genet B Neuropsychiatr Genet 153B:909–918PubMedGoogle Scholar
  176. Perroud N, Uher R, Ng MY, Guipponi M, Hauser J, Henigsberg N, Maier W, Mors O, Gennarelli M, Rietschel M, Souery D, Dernovsek MZ, Stamp AS, Lathrop M, Farmer A, Breen G, Aitchison KJ, Lewis CM, Craig IW, McGuffin P (2012) Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project. Pharmacogenomics J 12:68–77PubMedGoogle Scholar
  177. Peterson E, Møller A, Doudet DJ, Bailey CJ, Hansen KV, Rodell A, Linnet J, Gjedde A (2010) Pathological gambling: relation of skin conductance response to dopaminergic neurotransmission and sensation-seeking. Eur Neuropsychopharmacol 20:766–775PubMedGoogle Scholar
  178. Pine DS, Coplan JD, Wasserman GA, Miller LS, Fried JE, Davies M, Cooper TB, Greenhill L, Shaffer D, Parsons B (1997) Neuroendocrine response to fenfluramine challenge in boys. Associations with aggressive behavior and adverse rearing. Arch Gen Psychiatry 54:839–846PubMedGoogle Scholar
  179. Placidi GP, Oquendo MA, Malone KM, Huang YY, Ellis SP, Mann JJ (2001) Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels. Biol Psychiatry 50:783–791PubMedGoogle Scholar
  180. Płocka-Lewandowska M, Araszkiewicz A, Rybakowski JK (2001) Dexamethasone suppression test and suicide attempts in schizophrenic patients. Eur Psychiatry 16:428–431PubMedGoogle Scholar
  181. Poulter MO, Du L, Weaver IC, Palkovits M, Faludi G, Merali Z, Szyf M, Anisman H (2008) GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry 64:645–652PubMedGoogle Scholar
  182. Premkumar P, Ettinger U, Inchley-Mort S, Sumich A, Williams SC, Kuipers E, Kumari V (2012) Neural processing of social rejection: the role of schizotypal personality traits. Hum Brain Mapp 33:695–706PubMedGoogle Scholar
  183. Preti A (2005) Suicide among animals: clues from folklore that may prevent suicidal behaviour in human beings. Psychol Rep 97:547–558PubMedGoogle Scholar
  184. Raz N, Rodrigue KM, Kennedy KM, Land S (2009) Genetic and vascular modifiers of age-sensitive cognitive skills: effects of COMT, BDNF, ApoE, and hypertension. Neuropsychology 23:105–116PubMedGoogle Scholar
  185. Reppermund S, Ising M, Lucae S, Zihl J (2009) Cognitive impairment in unipolar depression is persistent and non-specific: further evidence for the final common pathway disorder hypothesis. Psychol Med 39:603–614PubMedGoogle Scholar
  186. Reuter M, Peters K, Schroeter K, Koebke W, Lenardon D, Bloch B, Hennig J (2005) The influence of the dopaminergic system on cognitive functioning: a molecular genetic approach. Behav Brain Res 164:93–99PubMedGoogle Scholar
  187. Rogers J, Martin LJ, Comuzzie AG, Mann JJ, Manuck SB, Leland M, Kaplan JR (2004) Genetics of monoamine metabolites in baboons: overlapping sets of genes influence levels of 5-hydroxyindolacetic acid, 3-hydroxy-4-methoxyphenylglycol, and homovanillic acid. Biol Psychiatry 55:739–744PubMedGoogle Scholar
  188. Romero L, Artigas F (1997) Preferential potentiation of the effects of serotonin uptake inhibitors by 5-HT1A receptor antagonists in the dorsal raphe pathway: role of somatodendritic autoreceptors. J Neurochem 68:2593–2603PubMedGoogle Scholar
  189. Rosel P, Arranz B, Vallejo J, Oros M, Crespo JM, Menchon JM, Navarro MA (1998) Variations in [3H]imipramine and 5-HT2A but not [3H]paroxetine binding sites in suicide brains. Psychiatry Res 82:161–170PubMedGoogle Scholar
  190. Rosel P, Arranz B, Urretavizcaya M, Oros M, San L, Navarro MA (2004) Altered 5-HT2A and 5-HT4 postsynaptic receptors and their intracellular signalling systems IP3 and cAMP in brains from depressed violent suicide victims. Neuropsychobiology 49:189–195PubMedGoogle Scholar
  191. Rotondo A, Schuebel K, Bergen A, Aragon R, Virkkunen M, Linnoila M, Goldman D, Nielsen D (1999) Identification of four variants in the tryptophan hydroxylase promoter and association to behavior. Mol Psychiatry 4:360–368PubMedGoogle Scholar
  192. Roy A (1993) Genetic and biologic risk factors for suicide in depressive disorders. Psychiatr Q 64:345–358PubMedGoogle Scholar
  193. Rujescu D, Giegling I, Sato T, Hartmann AM, Möller HJ (2003) Genetic variations in tryptophan hydroxylase in suicidal behavior: analysis and meta-analysis. Biol Psychiatry 54:465–473PubMedGoogle Scholar
  194. Rushton JP, Fulker DW, Neale MC, Nias DK, Eysenck HJ (1986) Altruism and aggression: the heritability of individual differences. J Pers Soc Psychol 50:1192–1198PubMedGoogle Scholar
  195. Russcher H, van Rossum EF, de Jong FH, Brinkmann AO, Lamberts SW, Koper JW (2005) Increased expression of the glucocorticoid receptor-A translational isoform as a result of the ER22/23EK polymorphism. Mol Endocrinol 19:1687–1696PubMedGoogle Scholar
  196. Sabol SZ, Hu S, Hamer D (1998) A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103:273–279PubMedGoogle Scholar
  197. Saetre P, Lundmark P, Wang A, Hansen T, Rasmussen HB, Djurovic S, Melle I, Andreassen OA, Werge T, Agartz I, Hall H, Terenius L, Jönsson EG (2010) The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case–control study and meta-analysis. Am J Med Genet B Neuropsychiatr Genet 153B:387–396PubMedGoogle Scholar
  198. Saiz PA, García-Portilla MP, Paredes B, Arango C, Morales B, Alvarez V, Coto E, Bascaran MT, Bousoño M, Bobes J (2008) Association between the A-1438G polymorphism of the serotonin 2A receptor gene and nonimpulsive suicide attempts. Psychiatr Genet 18:213–218PubMedGoogle Scholar
  199. Samuelsson M, Jokinen J, Nordström AL, Nordström P (2006) CSF 5-HIAA, suicide intent and hopelessness in the prediction of early suicide in male high-risk suicide attempters. Acta Psychiatr Scand 113:44–47PubMedGoogle Scholar
  200. Sarosi A, Gonda X, Balogh G, Domotor E, Szekely A, Hejjas K, Sasvari-Szekely M, Faludi G (2008) Association of the STin2 polymorphism of the serotonin transporter gene with a neurocognitive endophenotype in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32:1667–1772PubMedGoogle Scholar
  201. Sawiniec J, Borkowski K, Ginalska G, Lewandowska-Stanek H (2007) Association between 5-hydroxytryptamine 1A receptor gene polymorphism and suicidal behavior. Przegl Lek 64:208–211PubMedGoogle Scholar
  202. Scherk H, Gruber O, Menzel P, Schneider-Axmann T, Kemmer C, Usher J, Reith W, Meyer J, Falkai P (2009) 5-HTTLPR genotype influences amygdala volume. Eur Arch Psychiatry Clin Neurosci 259(4):212–217PubMedGoogle Scholar
  203. Schosser A, Butler AW, Ising M, Perroud N, Uher R, Ng MY, Cohen-Woods S, Craddock N, Owen MJ, Korszun A, Jones L, Jones I, Gill M, Rice JP, Maier W, Mors O, Rietschel M, Lucae S, Binder EB, Preisig M, Perry J, Tozzi F, Muglia P, Aitchison KJ, Breen G, Craig IW, Farmer AE, Müller-Myhsok B, McGuffin P, Lewis CM (2011) Genomewide association scan of suicidal thoughts and behaviour in major depression. PLoS One 6:e20690PubMedGoogle Scholar
  204. Schug RA, Raine A, Wilcox RR (2007) Psychophysiological and behavioural characteristics of individuals comorbid for antisocial personality disorder and schizophrenia-spectrum personality disorder. Br J Psychiatry 191:408–414PubMedGoogle Scholar
  205. Schüle C, Zill P, Baghai TC, Eser D, Zwanzger P, Wenig N, Rupprecht R, Bondy B (2006) Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients. Psychoneuroendocrinology 31:1019–1025PubMedGoogle Scholar
  206. Seligman ME, Maier SF (1967) Failure to escape traumatic shock. J Exp Psychol 74(1):1–9PubMedGoogle Scholar
  207. Serretti A (2002) Lithium long-term treatment in mood disorders: clinical and genetic predictors. Pharmacogenomics 3:117–129PubMedGoogle Scholar
  208. Serretti A, Mandelli L, Giegling I, Schneider B, Hartmann AM, Schnabel A, Maurer K, Möller HJ, Rujescu D (2007) HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers. Am J Med Genet B Neuropsychiatr Genet 144B:291–299PubMedGoogle Scholar
  209. Shalev I, Lerer E, Israel S, Uzefovsky F, Gritsenko I, Mankuta D, Ebstein RP, Kaitz M (2009) BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions. Psychoneuroendocrinology 34:382–388PubMedGoogle Scholar
  210. Shelton RC, Sanders-Bush E, Manier DH, Lewis DA (2009) Elevated 5-HT 2A receptors in postmortem prefrontal cortex in major depression is associated with reduced activity of protein kinase A. Neuroscience 158:1406–1415PubMedGoogle Scholar
  211. Sher L (2007) The role of the hypothalamic–pituitary–adrenal axis dysfunction in the pathophysiology of alcohol misuse and suicidal behavior in adolescents. Int J Adolesc Med Health 19:3–9PubMedGoogle Scholar
  212. Shih JC, Grimsby J, Chen K, Zhu QS (1993) Structure and promoter organization of the human monoamine oxidase A and B genes. J Psychiatry Neurosci 18:25–32PubMedGoogle Scholar
  213. Siever LJ (2005) Endophenotypes in the personality disorders. Dialogues Clin Neurosci 7:139–151PubMedGoogle Scholar
  214. Simeon D, Knutelska M, Smith L, Baker BR, Hollander E (2007) A preliminary study of cortisol and norepinephrine reactivity to psychosocial stress in borderline personality disorder with high and low dissociation. Psychiatry Res 149:177–184PubMedGoogle Scholar
  215. Skodol AE, Siever LJ, Livesley WJ, Gunderson JG, Pfohl B, Widiger TA (2002) The borderline diagnosis II: biology, genetics, and clinical course. Biol Psychiatry 51:951–963PubMedGoogle Scholar
  216. Solís-Ortiz S, Pérez-Luque E, Morado-Crespo L, Gutiérrez-Muñoz M (2010) Executive functions and selective attention are favored in middle-aged healthy women carriers of the Val/Val genotype of the catechol-o-methyltransferase gene: a behavioral genetic study. Behav Brain Funct 6:67PubMedGoogle Scholar
  217. Souza RP, Romano-Silva MA, Lieberman JA, Meltzer HY, MacNeil LT, Culotti JG, Kennedy JL, Wong AH (2010) Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response. J Psychiatr Res 44:700–706PubMedGoogle Scholar
  218. Speed M, Ruxton GD (2002) Animal behaviour: evolution of suicidal signals. Nature 416(6879):375PubMedGoogle Scholar
  219. Statham DJ, Heath AC, Madden PA, Bucholz KK, Bierut L, Dinwiddie SH, Slutske WS, Dunne MP, Martin NG (1998) Suicidal behaviour: an epidemiological and genetic study. Psychol Med 28(4):839–855PubMedGoogle Scholar
  220. Stins JF, van Baal GC, Polderman TJ, Verhulst FC, Boomsma DI (2004) Heritability of Stroop and flanker performance in 12-year old children. BMC Neurosci 5:49PubMedGoogle Scholar
  221. Stockmeier CA, Shapiro LA, Dilley GE, Kolli TN, Friedman L, Rajkowska G (1998) Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci 18:7394–7401PubMedGoogle Scholar
  222. Storrie MC, Doerr HO, Johnson MH (1981) Skin conductance characteristics of depressed subjects before and after therapeutic intervention. J Nerv Ment Dis 169:176–179PubMedGoogle Scholar
  223. Strous RD, Ritsner MS, Adler S, Ratner Y, Maayan R, Kotler M, Lachman H, Weizman A (2009) Improvement of aggressive behavior and quality of life impairment following S-adenosyl-methionine (SAM-e) augmentation in schizophrenia. Eur Neuropsychopharmacol 19:14–22PubMedGoogle Scholar
  224. Sublette ME, Baca-Garcia E, Parsey RV, Oquendo MA, Rodrigues SM, Galfalvy H, Huang YY, Arango V, Mann JJ (2008) Effect of BDNF val66met polymorphism on age-related amygdala volume changes in healthy subjects. Prog Neuropsychopharmacol Biol Psychiatry 32:1652–1655PubMedGoogle Scholar
  225. Suzuki T, Lu MS, Motegi H, Yoshii T, Misawa M (1992) Genetic differences in the development of physical dependence upon diazepam in Lewis and Fischer 344 inbred rat strains. Pharmacol Biochem Behav 43:387–393PubMedGoogle Scholar
  226. Swan GE, Carmelli D (2002) Evidence for genetic mediation of executive control: a study of aging male twins. J Gerontol B Psychol Sci Soc Sci 57:P133–P143PubMedGoogle Scholar
  227. Tamura Y, Kunugi H, Ohashi J, Hohjoh H (2007) Epigenetic aberration of the human REELIN gene in psychiatric disorders. Mol Psychiatry 12:519, 593–600PubMedGoogle Scholar
  228. Thompson AH (2008) Younger onset of depression is associated with greater suicidal intent. Soc Psychiatry Psychiatr Epidemiol 43:538–544PubMedGoogle Scholar
  229. Thorell LH (1987) Electrodermal activity in suicidal and nonsuicidal depressive patients and in matched healthy subjects. Acta Psychiatr Scand 76:420–430PubMedGoogle Scholar
  230. Thorell LH (2009) Valid electrodermal hyporeactivity for depressive suicidal propensity offers links to cognitive theory. Acta Psychiatr Scand 119:338–349PubMedGoogle Scholar
  231. Thorell LH, Kjellman BF, d’Elia G, Kågedal B (1988) Electrodermal activity in relation to cortisol dysregulation in depressive patients. Acta Psychiatr Scand 78:743–753PubMedGoogle Scholar
  232. Tidemalm D, Runeson B, Waern M, Frisell T, Carlström E, Lichtenstein P, Långström N (2011) Familial clustering of suicide risk: a total population study of 11.4 million individuals. Psychol Med 1:1–8Google Scholar
  233. Tiihonen J, Kuikka JT, Bergström KA, Karhu J, Viinamäki H, Lehtonen J, Hallikainen T, Yang J, Hakola P (1997) Single-photon emission tomography imaging of monoamine transporters in impulsive violent behaviour. Eur J Nucl Med 24:1253–1260PubMedGoogle Scholar
  234. Torgersen S, Czajkowski N, Jacobson K, Reichborn-Kjennerud T, Røysamb E, Neale MC, Kendler KS (2008) Dimensional representations of DSM-IV cluster B personality disorders in a population-based sample of Norwegian twins: a multivariate study. Psychol Med 38(11):1617–1625PubMedGoogle Scholar
  235. Turecki G, Brière R, Dewar K, Antonetti T, Lesage AD, Séguin M, Chawky N, Vanier C, Alda M, Joober R, Benkelfat C, Rouleau GA (1999) Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry 156:1456–1458PubMedGoogle Scholar
  236. Turecki G, Zhu Z, Tzenova J, Lesage A, Séguin M, Tousignant M, Chawky N, Vanier C, Lipp O, Alda M, Joober R, Benkelfat C, Rouleau GA (2001) TPH and suicidal behavior: a study in suicide completers. Mol Psychiatry 6:98–102PubMedGoogle Scholar
  237. Turecki G, Sequeira A, Gingras Y, Séguin M, Lesage A, Tousignant M, Chawky N, Vanier C, Lipp O, Benkelfat C, Rouleau GA (2003) Suicide and serotonin: study of variation at seven serotonin receptor genes in suicide completers. Am J Med Genet B Neuropsychiatr Genet 118:36–40Google Scholar
  238. Uhart M, McCaul ME, Oswald LM, Choi L, Wand GS (2004) GABRA6 gene polymorphism and an attenuated stress response. Mol Psychiatry 9:998–1006PubMedGoogle Scholar
  239. Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Mann JJ, Arango V (2012) Neuron density and serotonin receptor binding in prefrontal cortex in suicide. Int J Neuropsychopharmacol 15:435–447PubMedGoogle Scholar
  240. van den Akker EL, Russcher H, van Rossum EF, Brinkmann AO, de Jong FH, Hokken A, Pols HA, Koper JW, Lamberts SW (2006) Glucocorticoid receptor polymorphism affects transrepression but not transactivation. J Clin Endocrinol Metab 91:2800–2803PubMedGoogle Scholar
  241. van Heeringen K, Audenaert K, Van de Wiele L, Verstraete A (2000) Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity. J Affect Disord 60(3):181–189PubMedGoogle Scholar
  242. van Heeringen C, Audenaert K, Van Laere K, Dumont F, Slegers G, Mertens J, Dierckx RA (2003) Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide. J Affect Disord 74:149–158PubMedGoogle Scholar
  243. van Leeuwen N, Kumsta R, Entringer S, de Kloet ER, Zitman FG, DeRijk RH, Wüst S (2010) Functional mineralocorticoid receptor (MR) gene variation influences the cortisol awakening response after dexamethasone. Psychoneuroendocrinology 35(3):339–349PubMedGoogle Scholar
  244. van Leeuwen N, Bellingrath S, de Kloet ER, Zitman FG, DeRijk RH, Kudielka BM, Wüst S (2011) Human mineralocorticoid receptor (MR) gene haplotypes modulate MR expression and transactivation: implication for the stress response. Psychoneuroendocrinology 36:699–709PubMedGoogle Scholar
  245. van Rossum EF, Lamberts SW (2004) Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res 59:333–357PubMedGoogle Scholar
  246. van Rossum EF, Koper JW, van den Beld AW, Uitterlinden AG, Arp P, Ester W, Janssen JA, Brinkmann AO, de Jong FH, Grobbee DE, Pols HA, Lamberts SW (2003) Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf) 59:585–592Google Scholar
  247. Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V (1992) Multiple dopamine D4 receptor variants in the human population. Nature 358:149–152PubMedGoogle Scholar
  248. Verma R, Holmans P, Knowles JA, Grover D, Evgrafov OV, Crowe RR, Scheftner WA, Weissman MM, DePaulo JR Jr, Potash JB, Levinson DF (2008) Linkage disequilibrium mapping of a chromosome 15q25-26 major depression linkage region and sequencing of NTRK3. Biol Psychiatry 63:1185–1189PubMedGoogle Scholar
  249. Videtic A, Zupanc T, Pregelj P, Balazic J, Tomori M, Komel R (2009) Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C>G in Slovenian suicide victims. Eur Arch Psychiatry Clin Neurosci 259(4):234–238PubMedGoogle Scholar
  250. Volavka J, Bilder R, Nolan K (2004) Catecholamines and aggression: the role of COMT and MAO polymorphisms. Ann N Y Acad Sci 1036:393–398PubMedGoogle Scholar
  251. Voracek M, Loibl LM (2007) Genetics of suicide: a systematic review of twin studies. Wien Klin Wochenschr 119:463–475PubMedGoogle Scholar
  252. Walther DJ, Bader M (2003) A unique central tryptophan hydroxylase isoform. Biochem Pharmacol 66:1673–1680PubMedGoogle Scholar
  253. Walther DJ, Peter JU, Bashammakh S, Hörtnagl H, Voits M, Fink H, Bader M (2003) Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299:76PubMedGoogle Scholar
  254. Way BM, Taylor SE, Eisenberger NI (2009) Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. Proc Natl Acad Sci USA 106:15079–15084PubMedGoogle Scholar
  255. Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann J, Lunde I (1986) Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry 43:923–929PubMedGoogle Scholar
  256. Williams RB, Marchuk DA, Gadde KM, Barefoot JC, Grichnik K, Helms MJ, Kuhn CM, Lewis JG, Schanberg SM, Stafford-Smith M, Suarez EC, Clary GL, Svenson IK, Siegler IC (2003) Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology 28:533–541PubMedGoogle Scholar
  257. Willour VL, Zandi PP, Badner JA, Steele J, Miao K, Lopez V, MacKinnon DF, Mondimore FM, Schweizer B, McInnis MG, Miller EB, Depaulo JR Jr, Gershon ES, McMahon FJ, Potash JB (2007) Attempted suicide in bipolar disorder pedigrees: evidence for linkage to 2p12. Biol Psychiatry 61:725–727PubMedGoogle Scholar
  258. Willour VL, Seifuddin F, Mahon PB, Jancic D, Pirooznia M, Steele J, Schweizer B, Goes FS, Mondimore FM, Mackinnon DF; Bipolar Genome Study Consortium, Perlis RH, Lee PH, Huang J, Kelsoe JR, Shilling PD, Rietschel M, Nöthen M, Cichon S, Gurling H, Purcell S, Smoller JW, Craddock N, DePaulo JR Jr, Schulze TG, McMahon FJ, Zandi PP, Potash JB (2012) A genome-wide association study of attempted suicide. Mol Psychiatry 17:433–444PubMedGoogle Scholar
  259. Wolfersdorf M, Straub R (1994) Electrodermal reactivity in male and female depressive patients who later died by suicide. Acta Psychiatr Scand 89:279–284PubMedGoogle Scholar
  260. Wrzosek M, Łukaszkiewicz J, Wrzosek M, Serafin P, Jakubczyk A, Klimkiewicz A, Matsumoto H, Brower KJ, Wojnar M (2011) Association of polymorphisms in HTR2A, HTR1A and TPH2 genes with suicide attempts in alcohol dependence: a preliminary report. Psychiatry Res 190:149–151PubMedGoogle Scholar
  261. Wüst S, Van Rossum EF, Federenko IS, Koper JW, Kumsta R, Hellhammer DH (2004) Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress. J Clin Endocrinol Metab 89:565–573PubMedGoogle Scholar
  262. Zalsman G, Huang YY, Harkavy-Friedman JM, Oquendo MA, Ellis SP, Mann JJ (2005) Relationship of MAO-A promoter (u-VNTR) and COMT (V158M) gene polymorphisms to CSF monoamine metabolites levels in a psychiatric sample of caucasians: a preliminary report. Am J Med Genet B Neuropsychiatr Genet 132B:100–103PubMedGoogle Scholar
  263. Zalsman G, Patya M, Frisch A, Ofek H, Schapir L, Blum I, Harell D, Apter A, Weizman A, Tyano S (2011) Association of polymorphisms of the serotonergic pathways with clinical traits of impulsive-aggression and suicidality in adolescents: a multi-center study. World J Biol Psychiatry 12:33–41PubMedGoogle Scholar
  264. Zhang Y, Damjanoska KJ, Carrasco GA, Dudas B, D’Souza DN, Tetzlaff J, Garcia F, Hanley NR, Scripathirathan K, Petersen BR, Gray TS, Battaglia G, Muma NA, Van de Kar LD (2002) Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (−)DOI. J Neurosci 22:9635–9642PubMedGoogle Scholar
  265. 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 Psychiatry 62:1109–1118PubMedGoogle Scholar
  266. Zill P, Büttner A, Eisenmenger W, Bondy B, Ackenheil M (2004a) Regional mRNA expression of a second tryptophan hydroxylase isoform in postmortem tissue samples of two human brains. Eur Neuropsychopharmacol 14:282–284PubMedGoogle Scholar
  267. Zill P, Büttner A, Eisenmenger W, Möller HJ, Bondy B, Ackenheil M (2004b) Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims. Biol Psychiatry 56:581–586PubMedGoogle Scholar
  268. Zill P, Büttner A, Eisenmenger W, Möller HJ, Ackenheil M, Bondy B (2005) Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study. J Psychiatr Res 41:168–173PubMedGoogle Scholar
  269. Zill P, Büttner A, Eisenmenger W, Müller J, Möller HJ, Bondy B (2009) Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain. Neuroscience 159:1274–1282PubMedGoogle Scholar
  270. Zisook S, Rush AJ, Lesser I, Wisniewski SR, Trivedi M, Husain MM, Balasubramani GK, Alpert JE, Fava M (2007) Preadult onset vs. adult onset of major depressive disorder: a replication study. Acta Psychiatr Scand 115:196–205PubMedGoogle Scholar
  271. Zubenko GS, Maher BS, Hughes HB 3rd, Zubenko WN, Scott Stiffler J, Marazita ML (2004) Genome-wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet 129B:47–54PubMedGoogle Scholar
  272. Zupanc T, Pregelj P, Tomori M, Komel R, Paska AV (2010) No association between polymorphisms in four serotonin receptor genes, serotonin transporter gene and alcohol-related suicide. Psychiatr Danub 22:522–527PubMedGoogle Scholar

Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2012

Authors and Affiliations

  • Dimitry A. Chistiakov
    • 1
    Email author
  • Zurab I. Kekelidze
    • 2
  • Vladimir P. Chekhonin
    • 1
    • 2
  1. 1.Department of Medical NanobiotechnologyPirogov Russian State Medical UniversityMoscowRussia
  2. 2.Serbsky State Research Center of Forensic and Social PsychiatryMoscowRussia

Personalised recommendations