Experimental Brain Research

, Volume 230, Issue 4, pp 605–624 | Cite as

Serotonergic modulation of suicidal behaviour: integrating preclinical data with clinical practice and psychotherapy

  • Vasileios Boulougouris
  • Ioannis Malogiannis
  • George Lockwood
  • Iannis Zervas
  • Giuseppe Di Giovanni
Serotonin

Abstract

Many studies have provided important information regarding the anatomy, development and functional organization of the 5-HT system and the alterations in this system that are present within the brain of the suicidal patient. There is also a growing interest in genetic factors associated with suicide, since these may lead to the emergence of personality traits that prove to be long-term predictors of suicidal behaviour. This review will focus on presenting the scientific literature on the role of the serotonergic system in suicidal behaviour as well as dysfunctional attitudes and personality traits associated with the suicidal patient. The association of the serotonin transporter gene, the 5-HT2 receptors and its metabolite 5-hydroxyindoleacetic acid with suicidal behaviour and animal models that may capture the complexity of suicidal behaviour will be discussed. Finally, the relationship between neurobiological models and psychotherapeutic interventions for suicide prevention will be considered with a focus on Schema Therapy (an approach that has shown particular promise in the treatment of suicidal individuals with personality disorders), aiming to invite the reader to integrate some aspects of the neurobiology of human suicidal behaviour into a model of suicide that can be used in a clinical encounter.

Keywords

Suicide Serotonin 5-HT2 receptors 5-HTTLP Serotonin transporter Schema therapy Borderline personality disorder 

References

  1. Afifi TO, Boman J, Fleisher W, Sareen J (2009) The relationship between child abuse, parental divorce, and lifetime mental disorders and suicidality in a nationally representative adult sample. Child Abuse Negl 33:139–147PubMedCrossRefGoogle Scholar
  2. Agerbo E, Nordentoft M, Mortensen PB (2002) Familial, psychiatric, and socioeconomic risk factors for suicide in young people: nested case–control study. BMJ 13:325–374Google Scholar
  3. Angst J, Angst F, Gerber-Werder R, Gamma A (2005) Suicide in 406 mood-disorder patients with and without long-term medication: a 40–44 years’ follow-up. Arch Suicide Res 9:279–300PubMedCrossRefGoogle Scholar
  4. Antypa N, Van der Does W (2010) Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression. Genes Brain Behav 9:615–620PubMedGoogle Scholar
  5. Arango V, Ernsberger P, Marzuk PM et al (1990) Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 47:1038–1047PubMedCrossRefGoogle Scholar
  6. Arango V, Underwood M, Mann J (1992) Alterations in monoamine receptors in the brain of suicide victims. J Clin Psychopharm 12:8S–12SCrossRefGoogle Scholar
  7. 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 688:121–133PubMedCrossRefGoogle Scholar
  8. Arias B, Collier DA, Gasto C, Pintor L, Gutierrez B, Valles V, Fananas L (2001) Genetic variation in the 5-HT5A receptor gene in patients with bipolar disorder and major depression. Neurosci Lett 303:111–114PubMedCrossRefGoogle Scholar
  9. Arora RC, Meltzer HY (1989) Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 146:730–736PubMedGoogle Scholar
  10. Asberg M (1997) Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies. Ann N Y Acad Sci 836:158–181PubMedCrossRefGoogle Scholar
  11. Asberg M, Traskman L, Thoren P (1976) 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry 33:1193–1197PubMedCrossRefGoogle Scholar
  12. Attar-Levy D, Martinot J-L, Blin J et al (1999) The cortical serotonin2 receptors studied with positron emission tomography and [18F]-setoperone during depressive illness and anti-depressant treatment with clomipramine. Biol Psychiatry 45:180–186PubMedCrossRefGoogle Scholar
  13. Audenaert K, Van Laere K, Dumont F et al (2001) Decreased frontal serotonin 5-HT 2a receptor binding index in deliberate self-harm patients. Eur J Nucl Med 28:175–182PubMedCrossRefGoogle Scholar
  14. Auerbach JG, Faroy M, Ebstein R, Kahana M, Levine J (2001) The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants. J Child Psychol Psychiatry 42:777–783PubMedCrossRefGoogle Scholar
  15. Banki CM, Arato M, Papp Z, Kurcz M (1984) Biochemical markers in suicidal patients. Investigations with cerebrospinal fluid amine metabolites and neuroendocrine tests. J Affect Disord 6:341–350PubMedCrossRefGoogle Scholar
  16. Barraclough B, Bunch J, Nelson B, Sainsbury P (1974) A hundred cases of suicide: clinical aspects. Br J Psychiatry 125:355–373PubMedCrossRefGoogle Scholar
  17. Bayle FJ, Leroy S, Gourion D, Millet B, Olié JP, Poirier MF, Krebs MO (2003) 5HTTLPR polymorphism in schizophrenic patients: further support for association with violent suicide attempts. Am J Med Genet B Neuropsychiatr Genet 119:13–17CrossRefGoogle Scholar
  18. Beck A, Steer R, Kovacs M, Garrison B (1985) Hopelessness and eventual suicide: a 10-year prospective study of patients hospitalized with suicidal ideation. Am J Psychiatry 142:559–563PubMedGoogle Scholar
  19. Beck AT, Brown G, Steer RA (1989) Prediction of eventual suicide in psychiatric inpatients by clinical ratings of hopelessness. J Consult Clin Psychol 57:309–310PubMedCrossRefGoogle Scholar
  20. Bellivier F, Szöke A, Henry C, Lacoste J, Bottos C, Nosten-Bertrand M, Hardy P, Rouillon F, Launay JM, Laplanche JL, Leboyer M (2000) Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders. Biol Psychiatry 48:319–322PubMedCrossRefGoogle Scholar
  21. Belsky J, Pluess M (2009) Beyond diathesis stress: differential susceptibility to environmental influences. Psychol Bull 135:885–908PubMedCrossRefGoogle Scholar
  22. Berlie HD, Hurren KM (2013) Evaluation of lorcaserin for the treatment of obesity. Expert Opin Drug Metab Toxicol 9:1053–1059Google Scholar
  23. Biver F, Wikler D, Lotstra F, Damhaut P, Goldman S, Mendlewicz J (1997) Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex. Br J Psychiatry 171:444–448PubMedCrossRefGoogle Scholar
  24. Bondy B, Erfurth A, de Jonge S, Kruger M, Meyer H (2000) Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide. Mol Psychiatry 5:193–195PubMedCrossRefGoogle Scholar
  25. Bondy B, Buettner A, Zill P (2006) Genetics of suicide. Mol Psychiatry 11:336–351PubMedCrossRefGoogle Scholar
  26. Boothman L, Raley J, Denk F, Hirani E, Sharp T (2006) In vivo evidence that 5-HT(2C) receptors inhibit 5-HT neuronal activity via a GABAergic mechanism. Br J Pharmacol 149:861–869PubMedCrossRefGoogle Scholar
  27. Bortolato M, Pivac N, Muck Seler D, Nikolac Perkovic M, Pessia M, Di Giovanni G (2013) The role of the serotonergic system at the interface of aggression and suicide. Neuroscience 236:160–185PubMedCrossRefGoogle Scholar
  28. Boulougouris V, Chamberlain SR, Robbins TW (2009) Cross-species models of OC-spectrum disorders. Psychiatry Res 170:15–21PubMedCrossRefGoogle Scholar
  29. Bowlby J (1969) Attachment. Basic Books, New YorkGoogle Scholar
  30. Brezo J, Paris J, Turecki G (2006) Personality traits as correlates of suicidal ideation, suicide attempts, and suicide completions: a systematic review. Acta Psychiatr Scand 113:180–206PubMedCrossRefGoogle Scholar
  31. Brodsky BS, Stanley B (2008) Adverse childhood experiences and suicidal behavior. Psychiatr Clin North Am 31:223–235PubMedCrossRefGoogle Scholar
  32. Brodsky BS, Malone KM, Ellis SP, Dulit RA, Mann JJ (1997) Characteristics of borderline personality disorder associated with suicidal behavior. Am J Psychiatry 154:1715–1719PubMedGoogle Scholar
  33. Brown GL, Goodwin FK (1986) Cerebrospinal fluid correlates of suicide attempts and aggression. Ann N Y Acad Sci 487:175–188PubMedCrossRefGoogle Scholar
  34. Bubar MJ, Cunningham KA (2008) Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. Prog Brain Res 172:319–346PubMedCrossRefGoogle Scholar
  35. Canli T (2008) Toward a neurogenetic theory of neuroticism. Ann N Y Acad Sci 1129:153–174. doi:10.1196/annals.1417.022 PubMedCrossRefGoogle Scholar
  36. Canli T, Lesch KP (2007) Long story short: the serotonin transporter in emotion regulation and social cognition. Nat Neurosci 10:1103–1109PubMedCrossRefGoogle Scholar
  37. Cannon B, Mulroy R, Otto MW, Rosenbaum JF, Fava M, Nierenberg AA (1999) Dysfunctional attitudes and poor problem solving skills predict hopelessness in major depression. J Affect Disord 55:45–49PubMedCrossRefGoogle Scholar
  38. Carlsson A, Svennerholm L, Winblad B (1980) Seasonal and circadian monoamine variations in human brains examined post mortem. Acta Psychiatr Scand Suppl 280:75–85PubMedGoogle Scholar
  39. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389PubMedCrossRefGoogle Scholar
  40. Champoux M, Bennett A, Shannon C, Higley JD, Lesch KP, Suomi SJ (2002) Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Mol Psychiatry 7:1058–1063PubMedCrossRefGoogle Scholar
  41. Charney DS, Woods SW, Goodman WK, Heninger GR (1987) Serotonin function in anxiety. II. Effects of the serotonin agonist MCPP in panic disorder patients and healthy subjects. Psychopharmacology 92:14–24PubMedCrossRefGoogle Scholar
  42. Cirulli F, Francia N, Brachi I, Antonucci M, Aloe L, Suomi SJ, Alleva E (2009) Changes in plasma levels of BDNF and NGF reveal a gender-selective vulnerability to early adversity in rhesus macaques. Psychoneuroendocrinology 34:172–180PubMedCrossRefGoogle Scholar
  43. Clayden RC, Zaruk A, Meyre D, Thabane L, Samaan Z (2012) The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis. Transl Psychiatry 2:e166PubMedCrossRefGoogle Scholar
  44. Coccaro EF, Siever LJ, Klar HM, Mauer G, Cochrane K, Cooper TB et al (1989) Serotonin studies in patients with affective and personality disorders. Arch Gen Psychiatry 46:587–599PubMedCrossRefGoogle Scholar
  45. Coccaro EF, Kavoussi RJ, Hauger RL (1995) Physiological responses to d-fenfluramine and ipsapirone challenge correlate with indices of aggression in males with personality disorder. Int Clin Psychopharmacol 10:177–179Google Scholar
  46. Cole SW, Arevalo JM, Ruggiero AM, Heckman JJ, Suomi SJ (2012) Transcriptional modulation of the developing immune system by early life adversity. Proc Natl Acad Sci USA 109:20578–20583PubMedCrossRefGoogle Scholar
  47. Collado M, Serrano M (2010) Senescence in tumours: evidence from mice and humans. Nat Rev Cancer 10:51–57PubMedCrossRefGoogle Scholar
  48. Congdon E, Lesch KP, Canli T (2008) Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: implications for impulsivity. Am J Med Genet B Neuropsychiatr Genet 147B:27–32PubMedCrossRefGoogle Scholar
  49. Costa PT Jr, McCrae RR (1995) Domains and facets: hierarchical personality assessment using the revised NEO personality inventory. J Pers Assess 64:21–50PubMedCrossRefGoogle Scholar
  50. Costanza A, D’Orta I, Perroud N, Burkhardt S, Malafosse A, Mangin P, La Harpe R (2013) Neurobiology of suicide: do biomarkers exist? Int J Legal Med. doi:10.1007/s00414-013-0835-6
  51. 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 6:338–341PubMedCrossRefGoogle Scholar
  52. Courtet P, Picot MC, Bellivier F, Torres S, Jollant F, Michelon C, Castelnau D, Astruc B, Buresi C, Malafosse A (2004) Serotonin transporter gene may be involved in short-term risk of subsequent suicide attempts. Biol Psychiatry 55:46–51PubMedCrossRefGoogle 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. Crişan L, Pană S, Vulturar R, Heilman RM, Szekely R, Drugă B, Dragod N, Miu AC (2009) Genetic contributions of the serotonin transporter to social learning of fear and economic decision making. Soc Cogn Affect Neurosci 4:399–408PubMedCrossRefGoogle Scholar
  55. De Luca V, Tharmaligam S, Strauss J, Kennedy JL (2008) 5-ht2c receptor and mao-a interaction analysis: no association with suicidal behaviour in bipolar patients. Eur Arch Psychiatry Clin Neurosci 258:428–433PubMedCrossRefGoogle Scholar
  56. Dekeyne A, Brocco M, Loiseau F, Gobert A, Rivet JM, Di Cara B, Cremers TI, Flik G, Fone KC, Watson DJ, Papp M, Sharp T, Serres F, Cespuglio R, Olivier B, Chan JS, Lavielle G, Millan MJ (2012) S32212, a novel serotonin type 2C receptor inverse agonist/alpha2-adrenoceptor antagonist and potential antidepressant: II. A behavioral, neurochemical, and electrophysiological characterization. J Pharmacol Exp Ther 340:765–780PubMedCrossRefGoogle Scholar
  57. Dettmer AM, Novak MA, Suomi SDJ, Meyer JS (2012) Physiological and behavioral adaptations to relocation stress in differentially reared rhesus monkeys: hair cortisol as a biomarker for anxiety-related responses. Psychoneuroendocrinology 37:191–199PubMedCrossRefGoogle Scholar
  58. Dhaenen H, Bossuyt A, Mertens J, Bossuyt-Piron C, Gijesmans M, Kaufman L (1992) SPECT imaging of serotonin2 receptors in depression. Psychiatry Res Neuroimaging 45:227–237CrossRefGoogle Scholar
  59. Di Giovanni G, Di Matteo V, Di Mascio M, Esposito E (2000) Preferential modulation of mesolimbic vs. nigrostriatal dopaminergic function by serotonin(2C/2B) receptor agonists: a combined in vivo electrophysiological and microdialysis study. Synapse 35:53–61PubMedCrossRefGoogle Scholar
  60. Di Giovanni G, Di Matteo V, La Grutta V, Esposito E (2001) m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors. Neuroscience 103:111–116PubMedCrossRefGoogle Scholar
  61. Di Giovanni G, Di Matteo V, Pierucci M, Benigno A, Esposito E (2006) Central serotonin2C receptor: from physiology to pathology. Curr Top Med Chem 6:1909–1925PubMedCrossRefGoogle Scholar
  62. Di Giovanni G, Di Matteo V, Esposito E (eds) (2008) Serotonin–dopamine interaction: experimental evidence and therapeutic relevance. Elsevier, AmsterdamGoogle Scholar
  63. Di Giovanni G, Esposito E, Di Matteo V (eds) (2011) 5-HT2C receptors in the pathophysiology of CNS disease. Springer, New YorkGoogle Scholar
  64. Doudet D, Hommer D, Higley JD, Andreason PJ, Moneman R, Suomi SJ, Linnoila M (1995) Cerebral glucose metabolism, CSF 5-HIAA, and aggressive behavior in rhesus monkeys. Am J Psychiatry 152:1782–1787PubMedGoogle Scholar
  65. Dracheva S, Chin B, Haroutunian V (2008) Altered serotonin 2C receptor RNA splicing in suicide: association with editing. NeuroReport 19:379–382PubMedCrossRefGoogle Scholar
  66. Dulchin MC, Oquendo MA, Malone KM, Ellis SP, Li S, Mann JJ (2001) Prolactin response to DL-fenfluramine challenge before and after treatment with paroxetine. Neuropsychopharmacology 25:395–401PubMedCrossRefGoogle Scholar
  67. Dumais A, Lesage AD, Alda M, Rouleau G, Dumont M, Chawky N et al (2005a) Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men. Am J Psychiatry 162:2116–2124PubMedCrossRefGoogle Scholar
  68. Dumais A, Lesage AD, Lalovic A et al (2005b) Is violent method of suicide a behavioral marker of lifetime aggression? Am J Psychiatry 162:1375–1378PubMedCrossRefGoogle Scholar
  69. Duval F, Mokrani MC, Correa H, Bailey P, Valdebenito M, Monreal J, Crocq MA, Macher JP (2001) Lack of effect of HPA axis hyperactivity on hormonal responses to D-fenfluramine in major depressed patients: implications for pathogenesis of suicidal behaviour. Psychoneuroendocrinology 26:521–537PubMedCrossRefGoogle Scholar
  70. Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ (2002) The neural basis of mood-congruent processing biases in depression. Arch Gen Psychiatry 59:597–604PubMedCrossRefGoogle Scholar
  71. Evans E, Hawton K, Rodham K (2005) Suicidal phenomena and abuse in adolescents: a review of epidemiological studies. Child Abuse Negl 29:45–58PubMedCrossRefGoogle Scholar
  72. Fahlke C, Lorenz J, Long J, Champoux M, Suomi S, Higley J (2002) Rearing experiences and stress-induced plasma cortisol as early risk factors for excessive alcohol consumption in nonhuman primates. Alcohol Clin Exp Res 24:644–650CrossRefGoogle Scholar
  73. Farrell J, Shaw I, Webber M (2009) A schema-focused approach to group psychotherapy for outpatients with borderline personality disorder: a randomized controlled trial. J Behav Ther Exp Psychiatry 40:317–328PubMedCrossRefGoogle Scholar
  74. Fava M, Bless E, Otto M, Pava J, Rosenbaum J (1994) Dysfunctional attitudes in major depression changes with pharmacotherapy. J Nerv Ment Dis 182:45–49PubMedGoogle Scholar
  75. Frankle WG, Lombardo I, New AS et al (2005) Brain serotonin transporter distribution in subjects with impulsive aggressivity: A positron emission study with [11C]McN 5652. Am J Psychiatry 162:915–923PubMedCrossRefGoogle Scholar
  76. Frokjaer VG, Mortensen EL, Nielsen FA et al (2008) Frontolimbic serotonin 2A receptor binding in healthy subjects is associated with personality risk factors for affective disorder. Biol Psychiatry 63:569–576PubMedCrossRefGoogle Scholar
  77. Geyer MA, Markou A (1995) Animal models of psychiatric disorders. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation of progress. Raven Press, Ltd., New York, pp 787–798Google Scholar
  78. Ghaziuddin N, King CA, Welch KB, Zaccagnini J, Weidmer-Mikhail E, Mellow AM, Ghaziuddin M, Greden JF (2000) Serotonin dysregulation in adolescents with major depression: hormone response to meta-chlorophenylpiperazine (mCPP) infusion. Psychiatry Res 95:183–194PubMedCrossRefGoogle Scholar
  79. Giesen-Bloo J, van Dyck R, Spinhoven P, van Tilburg W, Carmen Dirksen C, van Asselt T, Kremers I, Nadort M, Arntz A (2006) Outpatient psychotherapy for borderline personality disorder: a randomized trial of schema focused therapy versus transference focused therapy. Arch Gen Psychiatry 63:649–658PubMedCrossRefGoogle Scholar
  80. Gonda X, Fountoulakis KN, Juhasz G, Rihmer Z, Lazary J, Laszik A, Akiskal HS, Bagdy G (2009) Association of the s allele of the 5-HTTLPR with neuroticism-related traits and temperaments in a psychiatrically healthy population. Eur Arch Psychiatry Clin Neurosci 259:106–113PubMedCrossRefGoogle Scholar
  81. Gonda X, Fountoulakis KN, Harro J, Pompili M, Akiskal HS, Bagdy G, Rihmer Z (2011) The possible contributory role of the S allele of 5-HTTLPR in the emergence of suicidality. J Psychopharmacol 25:857–866PubMedCrossRefGoogle Scholar
  82. Gonzalez A, Lovic V, Ward G, Wainwright P, Fleming A (2001) Intergenerational effects of complete maternal deprivation and replacement stimulation on maternal behavior and emotionality in female rats. Dev Psychobiol 38:11–32PubMedCrossRefGoogle Scholar
  83. Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645PubMedCrossRefGoogle Scholar
  84. Grant BF, Harford TC (1995) Comorbidity between DSM-IV alcohol use disorders and major depression: results of a national survey. Drug Alcohol Depend 39:197–206PubMedCrossRefGoogle Scholar
  85. Gunderson J, Lyons-Ruth K (2008) BPD’s interpersonal hypersensitivity phenotype: a gene-environment-developmental model. J Pers Disord 22:22–41PubMedCrossRefGoogle Scholar
  86. Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C (2002) Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 34:349–356PubMedCrossRefGoogle Scholar
  87. Hariri AR (2006) Genetically driven variation in serotonin function: impact on amygdale reactivity and individual differences in fearful and anxious personality. In: Canli T (ed) Biology of personality and individual differences. Guilford Press, New York, pp 295–316Google Scholar
  88. Harvey ML, Swallows CL, Cooper MA (2012) A double dissociation in the effects of 5-HT2A and 5-HT2C receptors on the acquisition and expression of conditioned defeat in Syrian hamsters. Behav Neurosci 126:530–537PubMedCrossRefGoogle Scholar
  89. Hawton K, van Heeringen K (2009) Suicide. Lancet 373:1372–1381PubMedCrossRefGoogle Scholar
  90. Higley JD, Suomi SJ (2011) Impulsivity and aggression as personality traits in nonhuman primates. In: Weiss A, King J, Murray L (eds) Personality and temperament in nonhuman primates. Springer, New York, NY, pp 257–284CrossRefGoogle Scholar
  91. Higley JD, Hasert ML, Suomi SJ, Linnoila M (1991) A new nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. Proc Natl Acad Sci USA 88:7261–7265PubMedCrossRefGoogle Scholar
  92. Hitzemann R (2000) Animal models of psychiatric disorders and their relevance to alcoholism. Alcohol Res Health 24:149–158PubMedGoogle Scholar
  93. Homberg JR, Lesch KP (2011) Looking on the bright side of serotonin transporter gene variation. Biol Psychiatry 69:513–519PubMedCrossRefGoogle Scholar
  94. Hoyer D, Pazos A, Probst A, Palacios JM (1986) Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res 376:97–107PubMedCrossRefGoogle Scholar
  95. Hrdina PD, Demeter E, Vu TB, Sotonyi P, Palkovits M (1993) 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala. Brain Res 614:37–44PubMedCrossRefGoogle Scholar
  96. Ichise M, Vines DC, Gura T, Anderson GM, Suomi SJ, Higley JD, Innis RB (2006) Effects of early life stress on [11C] DABS PET imaging of serotonin transporters in adolescent peer- and mother-reared rhesus monkeys. J Neurosci 26:4538–4543CrossRefGoogle Scholar
  97. Ingram RE, Luxton DD (2005) Vulnerability–stress models. In: Hankin BL, Abela JRZ (eds) Development of psychopathology: a vulnerability–stress perspective. Sage Publications, Thousand Oaks CA. Int Clin Psychopharmacol 10:177–179Google Scholar
  98. Jacobs B, Driscoll L, Schall M (1997) Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study. J Comp Neurol 386:661–680PubMedCrossRefGoogle Scholar
  99. Jahn AL, Fox AS, Abercrombie HC, Shelton SE, Oakes TR, Davidson RJ, Kalin NH (2010) Subgenual prefrontal cortex activity predicts individual differences in hypothalamic-pituitary-adrenal activity across different contexts. Biol Psychiatry 67:175–181PubMedCrossRefGoogle Scholar
  100. Jakab R, Goldman-Rakic P (1998) 5-Hydroxytryptamine2A serotonin receptors in the primate cerebral cortex: possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc Natl Acad Sci USA 95:735–740PubMedCrossRefGoogle Scholar
  101. Kalbitzer J, Frokjaer VG, Erritzoe D et al (2009) The personality trait openness is related to cerebral 5-HTT levels. Neuroimage 45:280–285PubMedCrossRefGoogle Scholar
  102. Koch W, Schaaff N, Popperl G et al (2007) [I-123]ADAM and SPECT in patients with borderline personality disorder and healthy control subjects. J Psychiatry Neurosci 32:234–240PubMedGoogle Scholar
  103. Kraemer GW, Clarke AS (1990) The behavioral neurobiology of self-injurious behavior in rhesus monkeys. Prog Neuropsychopharmacol Biol Psychiatry 14:S141–S168PubMedCrossRefGoogle Scholar
  104. Kraemer G, Ebert M, Schmidt D, McKinney W (1991) Strangers in a strange land: a psychobiological study of infant monkeys before and after separation from real or inanimate mothers. Child Dev 62:548–566PubMedCrossRefGoogle Scholar
  105. Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902PubMedCrossRefGoogle Scholar
  106. Kuhn KU, Joe AY, Meyer K, Reichmann K, Maier W, Rao ML, Reinhardt MJ, Biersack HJ, Quednow BB (2004) Neuroimaging and 5-HT2C receptor polymorphism: a HMPAO-SPECT study in healthy male probands using mCPP-challenge of the 5-HT2C receptor. Pharmacopsychiatry 37:286–291PubMedCrossRefGoogle Scholar
  107. Lanzas C, Ayscue P, Ivanek R, Gröhn YT (2010) Model or meal? Farm animal populations as models for infectious diseases of humans. Nat Rev Microbiol 8:139–148PubMedGoogle Scholar
  108. Lesch KP, Bengel D, Heils A et al (1996) Association of anxiety related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274:1527–1531PubMedCrossRefGoogle Scholar
  109. Lester D (1995) The concentration of neurotransmitter metabolites in the cerebrospinal fluid of suicidal individuals: a meta-analysis. Pharmacopsychiatry 28:45–50PubMedCrossRefGoogle Scholar
  110. Linehan MM, Armstrong HE, Suarez A, Allmon D, Heard HL (1991) Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Arch Gen Psychiatry 48:1060–1064PubMedCrossRefGoogle Scholar
  111. Linehan MM, Heard HL, Armstrong HE (1993) Naturalistic follow-up of a behavioral treatment for chronically parasuicidal borderline patients. Arch Gen Psych 50:971–974CrossRefGoogle Scholar
  112. Liu S, Bubar MJ, Lanfranco MF, Hillman GR, Cunningham KA (2007) Serotonin2C receptor localization in GABA neurons of the rat medial prefrontal cortex: implications for understanding the neurobiology of addiction. Neuroscience 146:1677–1688PubMedCrossRefGoogle Scholar
  113. Lockwood G, Perris P (2012) A new look at core emotional needs. In: van Vreeswijk M, Broerson J, Nadort M (eds) The Wiley-Blackwell handbook of schema therapy: theory Research and Practice. Wiley-Blackwell, Malden, MA, pp 41–66CrossRefGoogle Scholar
  114. Lovic V, Gonzalez A, Fleming A (2001) Maternally separated rats show deficits in maternal care in adulthood. Dev Psychobiol 39:19–33PubMedCrossRefGoogle Scholar
  115. Lu W, Mueser KT, Rosenberg SD, Jankowski MK (2008) Correlates of adverse childhood experiences among adults with severe mood disorders. Psychiatr Serv 59:1018–1026PubMedCrossRefGoogle Scholar
  116. Malone KM, Corbitt EM, Li S, Mann JJ (1996) Prolactin response to fenfluramine and suicide attempt lethality in major depression. Br J Psychiatry 168:324–329PubMedCrossRefGoogle Scholar
  117. Mann JJ (1995) Violence and aggression. In: Bloom FE, Kupfer D (eds) Psychopharmacology: the fourth generation of progress. Raven Press, New York, pp 1919–1928Google Scholar
  118. Mann J (1996) Postmortem studies of suicide victims. In: Watson S (ed) Biology of schizophrenia and affective disease. American Psychiatric Press Inc, LondonGoogle Scholar
  119. Mann JJ (1998) The neurobiology of suicide. Nat Med 4:25–30PubMedCrossRefGoogle Scholar
  120. Mann JJ, Malone KM (1997) Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients. Biol Psychiatry 41:162–171PubMedCrossRefGoogle Scholar
  121. Mann JJ, Stanley M, McBride PA, McEwen BS (1986) Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43:954–959PubMedCrossRefGoogle Scholar
  122. Mann JJ, Oquendo M, Underwood MD, Arango V (1999) The neurobiology of suicide risk: a review for the clinician. J Clin Psychiatry 60(suppl 2):7–11 (discussion 18–20, 113–116)Google Scholar
  123. 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 57:729–738PubMedCrossRefGoogle Scholar
  124. Martin CB, Ramond F, Farrington DT, Aguiar AS Jr, Chevarin C, Berthiau AS, Caussanel S, Lanfumey L, Herrick-Davis K, Hamon M, Madjar JJ, Mongeau R (2013) RNA splicing and editing modulation of 5-HT2C receptor function: relevance to anxiety and aggression in VGV mice. Mol Psychiatry 18:656–665PubMedCrossRefGoogle Scholar
  125. Matsumoto R, Ichise M, Ito H et al (2010) Reduced serotonin transporter binding in the insular cortex in patients with obsessive–compulsive disorder: a [11C]DASB PET study. Neuroimage 49:121–126PubMedCrossRefGoogle Scholar
  126. Matsunagaa M, Murakami H, Yamakawac K, Isowad T, Kasugaib K, Yonedab M, Kaneko H, Fukuyama S, Shinoda J, Yamada J, Ohira H (2010) Genetic variations in the serotonin transporter gene-linked polymorphic region influence attraction for a favourite person and the associated interactions between the central nervous and immune systems. Neurosci Lett 468:211–215CrossRefGoogle Scholar
  127. McBride PA, Brown RP, DeMeo M, Keilp J, Mieczkowski T, Mann JJ (1994) The relationship of platelet 5-HT2 receptor indices to major depressive disorder, personality traits, and suicidal behavior. Biol Psychiatry 35:295–308PubMedCrossRefGoogle Scholar
  128. McCann UD, Szabo Z, Seckin E et al (2005) Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB. Neuropsychopharmacology 30:1741–1750PubMedCrossRefGoogle Scholar
  129. McKinney WT (2001) Overview of the past contributions of animal models and their changing place in psychiatry. Semin Clin Neuropsychiatry 6:68–78PubMedCrossRefGoogle Scholar
  130. Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192PubMedCrossRefGoogle Scholar
  131. Meltzer C, Price J, Mathis C et al (1999) PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am J Psychiatry 156:1871–1878PubMedGoogle Scholar
  132. Meyer J, Kapur S, Houle S et al (1999) Prefrontal cortex 5-HT2 receptors in depression: a [18F] setoperone PET imaging study. Am J Psychiatry 156:1029–1034PubMedGoogle Scholar
  133. Meyer JH, Wilson AA, Ginovart N et al (2001) Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Am J Psychiatry 158:1843–1849PubMedCrossRefGoogle Scholar
  134. Meyer JH, McMain S, Kennedy SH et al (2003) Dysfunctional attitudes and 5-HT(2) receptors during depression and self-harm. Am J Psychiatry 160:90–99PubMedCrossRefGoogle Scholar
  135. Meyer JH, Houle S, Sagrati S et al (2004) Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry 61:1271–1279PubMedCrossRefGoogle Scholar
  136. Meyer JH, Wilson AA, Rusjan P et al (2008) Serotonin2A receptor binding potential in people with aggressive and violent behaviour. J Psychiatry Neurosci 33:499–508PubMedGoogle Scholar
  137. Middeldorp CM, de Geus E, Willemsen G, Hottenga J, Slagboom P, Boomsmal D (2010) The serotonin transporter gene length polymorphism (5-HTTLPR) and life events: no evidence for an interaction effect on neuroticism and anxious depressive symptoms. Twin Res Hum Genet 13:544–549PubMedCrossRefGoogle Scholar
  138. Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ (2004) Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography. Biol Psychiatry 55:217–224PubMedCrossRefGoogle Scholar
  139. Mitterschiffthaler MT, Williams SC, Walsh ND et al (2008) Neural basis of the emotional Stroop interference effect in major depression. Psychol Med 38:247–256PubMedCrossRefGoogle Scholar
  140. Munafo MR, Clark TG, Flint J (2005) Promise and pitfalls in the meta-analysis of genetic association studies: a response to Sen and Shinka. Mol Psychiatry 10:895–897CrossRefGoogle Scholar
  141. Munafo MR, Freimer NB, Ng W, Ophoff R, Veijola J, Miettunen J, Jarvelin M-R, Taanila A, Flint J (2009) 5-HTTLPR genotype and anxiety-related personality traits: a meta-analysis and new data. Am J Med Genet B Neuropsychiatr Genet 150B:271–281PubMedCrossRefGoogle Scholar
  142. Muris P (2006) Maladaptive schemas in non-clinical adolescents: relations to perceived parental rearing behaviours, big five personality factors, and psychopathological symptoms. Clin Psychol Psychother 13:405–413CrossRefGoogle Scholar
  143. Murphy DL, Lesch KP (2008) Targeting the murine serotonin transporter: insights into human neurobiology. Nat Rev Neurosci 9:85–96PubMedCrossRefGoogle Scholar
  144. Nadort M, Arntz A, Smit J, Giesen-Bloo J, Eikelenbooma M, Spinhoven P, van Asselt T, Wensing M, vanDyck R (2009) Implementation of out patient schema therapy for borderline personality disorder with versus without crisis support by the therapist outside office hours: a randomized trial. Behav Res Ther 47:961–973PubMedCrossRefGoogle Scholar
  145. Nelson EE, Herman KN, Barrett CE, Noble PL, Wojteczko K, Chisholm K, Delaney D, Ernst M, Fox NA, Suomi SJ, Winslow JT, Pine DS (2009) Adverse rearing experiences enhance responding to both aversive and rewarding stimuli in juvenile rhesus monkeys. Biol Psychiatry 66:702–704PubMedCrossRefGoogle Scholar
  146. Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13:1161–1169PubMedCrossRefGoogle Scholar
  147. Newport DJ, Stowe ZN, Nemeroff CB (2002) Parental depression: animal models of an adverse life event. Am J Psychiatry 159:1265–1283PubMedCrossRefGoogle Scholar
  148. Ni X, Chan K, Bulgin N, Sicard T, Bismil R, McMain S, Kennedy JL (2006) Association between serotonin transporter gene and borderline personality disorder. J Psychiatr Res 40:448–453PubMedCrossRefGoogle Scholar
  149. Norman W, Miller I, Dow M (1988) Characteristics of depressed patients with elevated levels of dysfunctional cognitions. Cog Ther Res 12:39–51CrossRefGoogle Scholar
  150. O’Regan D, Kwok RP, Yu PH, Bailey BA, Greenshaw AJ, Boulton AA (1987) A behavioural and neurochemical analysis of chronic and selective monoamine oxidase inhibition. Psychopharmacology 92:42–47PubMedCrossRefGoogle Scholar
  151. Oquendo MA, Mann JJ (2000) The biology of impulsivity and suicidality. Psychiatr Clin North Am 23:11–25PubMedCrossRefGoogle Scholar
  152. 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. A J Psychiatry 61:1433–1441CrossRefGoogle Scholar
  153. Panariello F, Javaid N, Luca V (2011) 5-HT2C receptors and suicidal behavior. In: Di Giovanni G, Esposito E, Di Matteo V (eds) 5-HT2C receptors in the pathophysiology of CNS disease, vol 22. Humana Press, New York, pp 261–274Google Scholar
  154. Pandey GN (1997) Altered serotonin function in suicide. Evidence from platelet and neuroendocrine studies. Ann N Y Acad Sci 836:182–200PubMedCrossRefGoogle Scholar
  155. Pandey GN (2013) Biological basis of suicide and suicidal behavior. Bipolar Disord. doi:10.1111/bdi.12089
  156. Pandey GN, Dwivedi Y, Rizavi HS et al (2002) Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims. Am J Psychiatry 159:419–429PubMedCrossRefGoogle Scholar
  157. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Faludi G, Sarosi A, Palkovits M (2006) Regional distribution and relative abundance of serotonin(2c) receptors in human brain: effect of suicide. Neurochem Res 31:167–176PubMedCrossRefGoogle Scholar
  158. Panskeep J (1998) Affective neuroscience: the foundations of human and animal emotions. Oxford University Press, New YorkGoogle Scholar
  159. 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 50:783–791PubMedCrossRefGoogle Scholar
  160. Pluess M, Belsky J, Way B, Baldwin M, Taylor S (2010) 5-HTTLPR moderates effects of current life events on neuroticism: differential susceptibility to environmental influences. Prog Neuropsychopharmacol Biol Psychiatry 34:1070–1074PubMedCrossRefGoogle Scholar
  161. Pompili M, Girardi P, Ruberto A, Tatarelli R (2005) Suicide in borderline personality disorder: a meta-analysis. Nord J Psychiatry 59:319PubMedCrossRefGoogle Scholar
  162. Pooley EC, Houston K, Hawton K, Harrison PJ (2003) Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in five other serotonergic genes. Psychol Med 33:775–783PubMedCrossRefGoogle Scholar
  163. Praschak-Rieder N, Wilson AA, Hussey D et al (2005) Effects of tryptophan depletion on the serotonin transporter in healthy humans. Biol Psychiatry 58:825–830PubMedCrossRefGoogle Scholar
  164. Preti A (2007) Suicide among animals: a review of evidence. Psychol Rep 101:831–848PubMedGoogle Scholar
  165. Preti A (2011) Animal model and neurobiology of suicide. Prog Neuropsychopharmacol Biol Psychiatry 35:818–830PubMedCrossRefGoogle Scholar
  166. Preti A, Miotto P (2005) Genetics, perinatal insult, and schizophrenia: the mechanism underlying an increased prevalence of perinatal complications among individuals with a diagnosis of schizophrenia? Curr Psychiatry Rev 1:139–150CrossRefGoogle Scholar
  167. Purselle DC, Nemeroff CB (2003) Serotonin transporter: a potential substrate in the biology of suicide. Neuropsychopharmacology 28:613–619PubMedCrossRefGoogle Scholar
  168. Qin P (2011) The impact of psychiatric illness on suicide: differences by diagnosis of disorders and by sex and age of subjects. J Psychiatr Res 45:1445–1452PubMedCrossRefGoogle Scholar
  169. Ramsden E, Wilson D (2010) The nature of suicide: science and the self-destructive animal. Endeavour 34:21–24PubMedCrossRefGoogle Scholar
  170. Reimold M, Smolka MN, Zimmer A et al (2007) Reduced availability of serotonin transporters in obsessive–compulsive disorder correlates with symptom severity—a [11C]DASB PET study. J Neural Transm 114:1603–1609PubMedCrossRefGoogle Scholar
  171. Rihmer Z (2007) Suicide risk in mood disorders. Curr Opin Psychiatry 20:17–22PubMedCrossRefGoogle Scholar
  172. Rijkeboer MM, de Boo GM (2010) Early maladaptive schemas in children: development and validation of the schema inventory for children. J Behav Ther Exp Psychiatry 41:102–109PubMedCrossRefGoogle Scholar
  173. Risch N, Herrell R, Liang KY, Lehner T, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Ries K, Merikangas KR (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301:2462–2471PubMedCrossRefGoogle Scholar
  174. Robins E, Murphy G, Wilkinson R, Gassner S, Kayes J (1959) Some clinical considerations in the prevention of suicide based on a study of 134 successful suicides. Am J Public Health 49:888–899CrossRefGoogle Scholar
  175. Roggenbach J, Müller-Oerlinghausen B, Franke L (2002) Suicidality, impulsivity and aggression–is there a link to 5HIAA concentration in the cerebrospinal fluid? Psychiatry Res 113:193–206PubMedCrossRefGoogle Scholar
  176. Rosell DR, Thompson JL, Slifstein M et al (2010) Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients. Biol Psychiatry 67:1154–1162PubMedCrossRefGoogle Scholar
  177. Rosenzweig-Lipson S, Sabb A, Stack G, Mitchell P, Lucki I, Malberg JE, Grauer S, Brennan J, Cryan JF, Sukoff Rizzo SJ, Dunlop J, Barrett JE, Marquis KL (2007) Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents. Psychopharmacology 192:159–170PubMedCrossRefGoogle Scholar
  178. Roy A, Ågren H, Pickar D, Linnoila M, Doran A, Cutler N, Paul SM (1986) Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression. Am J Psychiatry 143:1539–1545PubMedGoogle Scholar
  179. Rush AJ, Beck AT, Kovacs M, Weissenburger J, Hollon SD (1982) Comparison of the effects of cognitive therapy and pharmacotherapy on hopelessness and self-concept. Am J Psychiatry 139:862–866PubMedGoogle Scholar
  180. Ryding E, Ahnlide JA, Lindström M, Rosén I, Träskman-Bendz L (2006) Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy. Psychiatry Res 148:195–203PubMedCrossRefGoogle Scholar
  181. Salkovskis PM, Atha C, Storer D (1990) Cognitive-behavioural problem solving in the treatment of patients who repeatedly attempt suicide. A controlled trial. Br J Psychiatry 157:871–876PubMedCrossRefGoogle Scholar
  182. Samual DB, Widiger TA (2008) A meta-analytic review of the relationships between the five-factor model and DSM-IV-TR personality disorder: a facet level analysis. Clin Psychol Rev 28:1326–1342CrossRefGoogle Scholar
  183. Santana N, Bortolozzi A, Serrats J, Mengod G, Artigas F (2004) Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb Cortex 14:1100–1109PubMedCrossRefGoogle Scholar
  184. Saulsman LM, Page AC (2004) The five-factor model and personality disorder empirical literature: a meta-analytic review. Clin Psychol Rev 23:1055–1085PubMedCrossRefGoogle Scholar
  185. Schinka JA, Buschand RM, Robichaux-Keene N (2004) A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety. Mol Psychiatry 9:197–202PubMedCrossRefGoogle Scholar
  186. Schmuck K, Ullmer C, Engels P, Lubbert H (1994) Cloning and functional characterization of the human 5-HT2B serotonin receptor. FEBS Lett 342:85–90PubMedCrossRefGoogle Scholar
  187. Seligman ME (1972) Learned helplessness. Ann Rev Med 23:407–412PubMedCrossRefGoogle Scholar
  188. Selvaraj S, Hoshi R, Bhagwagar Z et al (2009) Brain serotonin transporter binding in former users of MDMA(‘ecstasy’). Br J Psychiatry 194:355–359PubMedCrossRefGoogle Scholar
  189. Sen SM, Burmeister D, Ghosh D (2004) Meta-analysis of the association between a serotonin transporter promoter polymorphism (5-HTTLPR) and anxiety-related personality traits. Am J Med Genet 127B:85–89PubMedCrossRefGoogle Scholar
  190. Serrats J, Mengod G, Cortes R (2005) Expression of serotonin 5-HT2C receptors in GABAergic cells of the anterior raphe nuclei. J Chem Neuroanat 29:83–91PubMedCrossRefGoogle Scholar
  191. Serretti A, Drago A, De Ronchi D (2007) HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies. Curr Med Chem 14:2053–2069PubMedCrossRefGoogle Scholar
  192. Serretti A, Calati R, Giegling I, Hartmann AM, Moller HJ, Rujescu D (2009) Serotonin receptor HTR1A and HTR2C variants and personality traits in suicide attempters and controls. J Psychiatr Res 43:519–525PubMedCrossRefGoogle Scholar
  193. Shannon C, Schwandt ML, Champoux M, Shoaf SE, Suomi SJ, Linnoila M, Higley JD (2005) Maternal absence and stability of individual differences in CSF 5-HIAA concentrations in rhesus monkey infants. Am J Psychiatry 162:1658–1664PubMedCrossRefGoogle Scholar
  194. Sharot T, Riccardi AM, Raio CM, Phelps EA (2007) Neural mechanisms mediating optimism bias. Nature 450:102–105PubMedCrossRefGoogle Scholar
  195. Simons AD, Murphy GE, Levine JL, Wetzel RD (1986) Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year. Arch Gen Psychiatry 43:43–48PubMedCrossRefGoogle Scholar
  196. Soloff PH, Price JC, Meltzer CC, Fabio A, Frank GK, Kaye WH (2007) 5HT2A receptor binding is increased in borderline personality disorder. Biol Psychiatry 62:580–587PubMedCrossRefGoogle Scholar
  197. Spinelli S, Chefer S, Suomi SJ, Barr CS, Stein E (2009) Early-life stress induces long-term morphological changes in primate brain. Arch Gen Psychiatry 66:658–665PubMedCrossRefGoogle Scholar
  198. Stanley M, Traskman-Bendz L, Dorovini-Zis K (1985) Correlations between aminergic metabolites simultaneously obtained from human CSF and brain. Life Sci 37:1279–1286PubMedCrossRefGoogle Scholar
  199. Stanley B, Molcho A, Stanley M, Winchel R, Gameroff MJ, Parsons B, Mann JJ (2000) Association of aggressive behavior with altered serotonergic function in patients who are not suicidal. Am J Psychiatry 157:609–614PubMedCrossRefGoogle Scholar
  200. Stefulj J, Buttner A, Skavic J, Zill P, Balija M, Eisenmenger W, Bondy B, Jernej B (2004) Serotonin 1B (5HT-1B) receptor polymorphism (G861C) in suicide victims: association studies in German and Slavic population. Am J Med Genet B Neuropsychiatr Genet 127B:48–50PubMedCrossRefGoogle Scholar
  201. Stein MB, Schork NJ, Gelernter J (2008) Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. Neuropsychopharmacology 33:312–319PubMedCrossRefGoogle Scholar
  202. Stockmeier CA (2003) Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 37:357–373PubMedCrossRefGoogle Scholar
  203. Stockmeier CA, Dilley GE, Shapiro LA, Overholser JC, Thompson PA, Meltzer HY (1997) Serotonin receptors in suicide victims with major depression. Neuropsychopharmacology 16:162–173PubMedCrossRefGoogle Scholar
  204. Suhara T, Takano A, Sudo Y et al (2003) High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography. Arch Gen Psychiatry 60:386–391PubMedCrossRefGoogle Scholar
  205. Suomi SJ (1997) Early determinants of behaviour: evidence from primate studies. Br Med Bull 53:170–184PubMedCrossRefGoogle Scholar
  206. Suomi SJ (2011) Risk, resilience, and gene-environment interplay in primates. J Can Acad Child Adolesc Psychiatry 20:289–297PubMedCrossRefGoogle Scholar
  207. Suominen K, Isometsa E, Suokas J, Haukka J, Achte K, Lonnqvist J (2004) Completed suicide after a suicide attempt: a 37-year follow-up study. Am J Psychiatry 161:562–563PubMedCrossRefGoogle Scholar
  208. Taylor SE, Way BM, Welch WT, Hilmert CJ, Lehman BJ, Eisenberger NI (2006) Early family environment, current adversity, the serotonin transporter promoter polymorphism, and depressive symptomatology. Biol Psychiatry 60:671–676PubMedCrossRefGoogle Scholar
  209. Takano A, Arakawa R, Hayashi M, Takahashi H, Ito H, Suhara T (2007) Relationship between neuroticism personality trait and serotonin transporter binding. Biol Psychiatry 62:588–592PubMedCrossRefGoogle Scholar
  210. Terracciano A, Balaci L, Thayer J, Scally M, Kokinos S, Ferrucci L (2009) Variants of the serotonin transporter gene and NEO-PI-R Neuroticism: no association in the BLSA and SardiNIA samples. Am J Med Genet B Neuropsychiatr Genet 150B:1070–1077PubMedCrossRefGoogle Scholar
  211. Thimm JC (2010) Personality and early maladaptive schemas: a five-factor model perspective. J Behav Ther Exp Psychiatry 41:373–380PubMedCrossRefGoogle Scholar
  212. Tiefenbacher S, Novak MA, Lutz CK, Meyer JS (2005) The physiology and neurochemistry of self-injurious behavior: a nonhuman primate model. Front Biosci 10:1–11PubMedCrossRefGoogle Scholar
  213. Todd KG, McManus DJ, Baker GB (1995) Chronic administration of the antidepressants phenelzine, desipramine, clomipramine, or maprotiline decreases binding to 5-hydroxytryptamine2A receptors without affecting benzodiazepine binding sites in rat brain. Cell Mol Neurobiol 15:361–370PubMedCrossRefGoogle Scholar
  214. Tondo L, Lepri B, Baldessarini RJ (2008) Suicidal status during antidepressant treatment in 789 Sardinian patients with major affective disorder. Acta Psychiatr Scand 118:106–115PubMedCrossRefGoogle Scholar
  215. Träskman L, Åsberg M, Bertilsson L, Sjöstrand L (1981) Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry 38:631–636PubMedCrossRefGoogle Scholar
  216. Turecki G, Briere R, Dewar K et al (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
  217. Turecki G, Sequeira A, Gingras Y, Seguin 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 118B:36–40PubMedCrossRefGoogle Scholar
  218. Turecki G, Ernst C, Jollant F, Labonté B, Mechawar N (2012) The neurodevelopmental origins of suicidal behavior. Trends Neurosci 35:14–23PubMedCrossRefGoogle Scholar
  219. Uher R, McGuffin P (2009) The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: update. Mol Psychiatry 1:18–22Google Scholar
  220. van den Boom DC, Hocksma JB (1994) The effect of infant irritability on mother-infant interaction: a growth curve analysis. Dev Psychol 30:581–590CrossRefGoogle Scholar
  221. van Heeringen C, Audenaert K, Van Laere K et al (2003) Prefrontal 5-HT2a receptor binding index, hopelessness and personality characteristics in attempted suicide. J Affect Disord 74:149–158PubMedCrossRefGoogle Scholar
  222. 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 259:234–238PubMedCrossRefGoogle Scholar
  223. Walker C, Scribner K, Cascio C, Dallman M (1991) The pituitary adrenocortical system of neonatal rats is responsive to stress throughout development in a time-dependent and stressor specific fashion. Endocrinology 128:1385–1395PubMedCrossRefGoogle Scholar
  224. Way BM, Taylor SE (2010) The serotonin transporter promoter polymorphism is associated with cortisol response to psychosocial stress. Biol Psychiatry 67:487–492PubMedCrossRefGoogle Scholar
  225. Weinstein T, Capitanio JP, Gosling SD (2008) Personality in animals. In: John OP, Robins RW, Pervin LA (eds) Handbook of personality, 3rd edn. Guilford Press, New York, pp 328–348Google Scholar
  226. Weiss D, Coccaro EF (1997) Neuroendocrine challenge studies of suicidal behavior. Psychiatr Clin North Am 20:563–579PubMedCrossRefGoogle Scholar
  227. Willis-Owen AG, Turri MG, Munafò MR, Surtees PG, Wainwright N, Brixey RD, Flint J (2005) The Serotonin transporter length polymorphism, neuroticism, and depression: a comprehensive assessment of association. Biol Psychiatry 58:451–456PubMedCrossRefGoogle Scholar
  228. Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN (1990) 5HT2 receptor changes in major depression. Biol Psychiatry 27:489–496PubMedCrossRefGoogle Scholar
  229. Young JE (2005) Young schema questionnaire: long form, version 3. Schema Therapy Institute, New YorkGoogle Scholar
  230. Young JE, Klosko JS, Weishaar ME (2003) Schema therapy: a practitioner’s guide. Guilford Press, NYGoogle Scholar
  231. Young K, Holcomb L, Bonkale W, Hicks P, Yazdani U, German D (2007) 5HTTLPR polymorphism and enlargement of the pulvinar: unlocking the backdoor to the limbic system. Biol Psychiatry 61:813–818PubMedCrossRefGoogle Scholar
  232. Zhang J, Shen Y, He G, Li X, Meng J, Guo S, Li H, Gu N, Feng G, He L (2008) Lack of association between three serotonin genes and suicidal behavior in Chinese psychiatric patients. Prog Neuropsychopharmacol Biol Psychiatry 32:467–471PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Vasileios Boulougouris
    • 1
    • 2
  • Ioannis Malogiannis
    • 1
    • 2
  • George Lockwood
    • 3
  • Iannis Zervas
    • 1
    • 2
  • Giuseppe Di Giovanni
    • 4
  1. 1.Greek Society of Schema TherapyAthensGreece
  2. 2.1st Department of PsychiatryEginition Hospital, Athens Medical SchoolAthensGreece
  3. 3.Schema Therapy Institute MidwestKalamazooUSA
  4. 4.Department of Physiology and Biochemistry, Faculty of Medicine and SurgeryUniversity of MaltaVallettaMalta

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