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Clinical and genetic factors associated with suicide in mood disorder patients

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Abstract

Suicidality is a continuum ranging from ideation to attempted and completed suicide, with a complex etiology involving both genetic heritability and environmental factors. The majority of suicide events occur in the context of psychiatric conditions, preeminently major depression and bipolar disorder. The present study investigates clinical factors associated with suicide in a sample of 553 mood disorder patients, recruited within the ‘Psy Pluriel’ center, Centre Européen de Psychologie Médicale, and the Department of Psychiatry of Erasme Hospital (Brussels). Furthermore, genetic association analyses examining polymorphisms within COMT, BDNF, MAPK1 and CREB1 genes were performed in a subsample of 259 bipolar patients. The presence or absence of a previous suicide attempt and of current suicide risk were assessed. A positive association with suicide attempt was reported for younger patients, females, lower educated, smokers, those with higher scores on depressive symptoms and higher functional disability and those with anxiety comorbidity and familial history of suicidality in first- and second-degree relatives. Anxiety disorder comorbidity was the stronger predictor of current suicide risk. No associations were found with polymorphisms within COMT and BDNF genes, whereas significant associations were found with variations in rs13515 (MAPK1) and rs6740584 (CREB1) polymorphisms. From a clinical perspective, our study proposes several clinical characteristics, such as increased depressive symptomatology, anxiety comorbidity, functional disability and family history of suicidality, as correlates associated with suicide. Genetic risk variants in MAPK1 and CREB1 genes might be involved in a dysregulation of inflammatory and neuroplasticity pathways and are worthy of future investigation.

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References

  1. Lester D, Abdel-Khalek AM (1999) Manic-depression, suicidality, and obsessive-compulsive tendencies. Psychol Rep 85:1100

    Article  CAS  PubMed  Google Scholar 

  2. Moffitt TE, Caspi A, Taylor A, Kokaua J, Milne BJ, Polanczyk G, Poulton R (2010) How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment. Psychol Med 40:899–909

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Tsuang MT, Taylor L, Faraone SV (2004) An overview of the genetics of psychotic mood disorders. J Psychiatr Res 38:3–15

    Article  PubMed  Google Scholar 

  4. Harris EC, Barraclough B (1997) Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry 170:205–228

    Article  CAS  PubMed  Google Scholar 

  5. Conwell Y, Duberstein PR, Cox C, Herrmann JH, Forbes NT, Caine ED (1996) Relationships of age and Axis I diagnoses in victims of completed suicide: a psychological autopsy study. Am J Psychiatry 153:1001–1008

    Article  CAS  PubMed  Google Scholar 

  6. Chen YW, Dilsaver SC (1996) Lifetime rates of suicide attempts among subjects with bipolar and unipolar disorders relative to subjects with other Axis I disorders. Biol Psychiatry 39:896–899

    Article  CAS  PubMed  Google Scholar 

  7. Angst J, Hengartner MP, Gamma A, von Zerssen D, Angst F (2013) Mortality of 403 patients with mood disorders 48 to 52 years after their psychiatric hospitalisation. Eur Arch Psychiatry Clin Neurosci 263:425–434

    Article  PubMed  Google Scholar 

  8. 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 161:1433–1441

    Article  PubMed  Google Scholar 

  9. Nivoli AM, Pacchiarotti I, Rosa AR, Popovic D, Murru A, Valenti M, Bonnin CM, Grande I, Sanchez-Moreno J, Vieta E, Colom F (2011) Gender differences in a cohort study of 604 bipolar patients: the role of predominant polarity. J Affect Disord 133:443–449

    Article  PubMed  Google Scholar 

  10. Victor SE, Klonsky ED (2014) Correlates of suicide attempts among self-injurers: a meta-analysis. Clin Psychol Rev 34:282–297

    Article  PubMed  Google Scholar 

  11. Angst J, Hengartner MP, Rogers J, Schnyder U, Steinhausen HC, Ajdacic-Gross V, Rossler W (2014) Suicidality in the prospective Zurich study: prevalence, risk factors and gender. Eur Arch Psychiatry Clin Neurosci 264:557–565

    Article  PubMed  Google Scholar 

  12. Coryell W, Fiedorowicz J, Leon AC, Endicott J, Keller MB (2013) Age of onset and the prospectively observed course of illness in bipolar disorder. J Affect Disord 146:34–38

    Article  PubMed Central  PubMed  Google Scholar 

  13. Goldstein TR, Ha W, Axelson DA, Goldstein BI, Liao F, Gill MK, Ryan ND, Yen S, Hunt J, Hower H, Keller M, Strober M, Birmaher B (2012) Predictors of prospectively examined suicide attempts among youth with bipolar disorder. Arch Gen Psychiatry 69:1113–1122

    Article  PubMed Central  PubMed  Google Scholar 

  14. Altamura AC, Dell’Osso B, Berlin HA, Buoli M, Bassetti R, Mundo E (2010) Duration of untreated illness and suicide in bipolar disorder: a naturalistic study. Eur Arch Psychiatry Clin Neurosci 260:385–391

    Article  PubMed  Google Scholar 

  15. Seemuller F, Meier S, Obermeier M, Musil R, Bauer M, Adli M, Kronmuller K, Holsboer F, Brieger P, Laux G, Bender W, Heuser I, Zeiler J, Gaebel W, Riedel M, Falkai P, Moller HJ (2014) Three-year long-term outcome of 458 naturalistically treated inpatients with major depressive episode: severe relapse rates and risk factors. Eur Arch Psychiatry Clin Neurosci 264:567–575

    Article  PubMed  Google Scholar 

  16. Hawton K, Sutton L, Haw C, Sinclair J, Harriss L (2005) Suicide and attempted suicide in bipolar disorder: a systematic review of risk factors. J Clin Psychiatry 66:693–704

    Article  PubMed  Google Scholar 

  17. Acosta FJ, Vega D, Torralba L, Navarro S, Ramallo-Farina Y, Fiuza D, Hernandez JL, Siris SG (2012) Hopelessness and suicidal risk in bipolar disorder. A study in clinically nonsyndromal patients. Compr Psychiatry 53:1103–1109

    Article  PubMed  Google Scholar 

  18. Coryell W, Young EA (2005) Clinical predictors of suicide in primary major depressive disorder. J Clin Psychiatry 66:412–417

    Article  PubMed  Google Scholar 

  19. Mann JJ, Waternaux C, Haas GL, Malone KM (1999) Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry 156:181–189

    CAS  PubMed  Google Scholar 

  20. Hawton K, Casanas ICC, Haw C, Saunders K (2013) Risk factors for suicide in individuals with depression: a systematic review. J Affect Disord 147:17–28

    Article  PubMed  Google Scholar 

  21. Valtonen HM, Suominen K, Mantere O, Leppamaki S, Arvilommi P, Isometsa E (2007) Suicidal behaviour during different phases of bipolar disorder. J Affect Disord 97:101–107

    Article  PubMed  Google Scholar 

  22. 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 28:839–855

    Article  CAS  PubMed  Google Scholar 

  23. Baldassano CF (2006) Illness course, comorbidity, gender, and suicidality in patients with bipolar disorder. J Clin Psychiatry 67(Suppl 11):8–11

    PubMed  Google Scholar 

  24. Neves FS, Malloy-Diniz LF, Barbosa IG, Brasil PM, Correa H (2009) Bipolar disorder first episode and suicidal behavior: are there differences according to type of suicide attempt? Rev Bras Psiquiatr 31:114–118

    PubMed  Google Scholar 

  25. Finseth PI, Morken G, Andreassen OA, Malt UF, Vaaler AE (2012) Risk factors related to lifetime suicide attempts in acutely admitted bipolar disorder inpatients. Bipolar Disord 14:727–734

    Article  PubMed  Google Scholar 

  26. Beghi M, Rosenbaum JF, Cerri C, Cornaggia CM (2013) Risk factors for fatal and nonfatal repetition of suicide attempts: a literature review. Neuropsychiatr Dis Treat 9:1725–1736

    PubMed Central  PubMed  Google Scholar 

  27. Nordstrom P, Asberg M, Aberg-Wistedt A, Nordin C (1995) Attempted suicide predicts suicide risk in mood disorders. Acta Psychiatr Scand 92:345–350

    Article  CAS  PubMed  Google Scholar 

  28. Antypa N, Antonioli M, Serretti A (2013) Clinical, psychological and environmental predictors of prospective suicide events in patients with bipolar disorder. J Psychiatr Res 47:1800–1808

    Article  PubMed  Google Scholar 

  29. McElroy SL, Frye MA, Hellemann G, Altshuler L, Leverich GS, Suppes T, Keck PE, Nolen WA, Kupka R, Post RM (2011) Prevalence and correlates of eating disorders in 875 patients with bipolar disorder. J Affect Disord 128:191–198

    Article  PubMed  Google Scholar 

  30. Simpson SG, Jamison KR (1999) The risk of suicide in patients with bipolar disorders. J Clin Psychiatry 60(Suppl 2):53–56 (discussion 75–56, 113–116)

    PubMed  Google Scholar 

  31. Pompili M, Serafini G, Innamorati M, Biondi M, Siracusano A, Di Giannantonio M, Giupponi G, Amore M, Lester D, Girardi P, Moller-Leimkuhler AM (2012) Substance abuse and suicide risk among adolescents. Eur Arch Psychiatry Clin Neurosci 262(6):469–485

  32. Dumais A, Lesage AD, Alda M, Rouleau G, Dumont M, Chawky N, Roy M, Mann JJ, Benkelfat C, Turecki G (2005) Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men. Am J Psychiatry 162:2116–2124

    Article  CAS  PubMed  Google Scholar 

  33. Maser JD, Akiskal HS, Schettler P, Scheftner W, Mueller T, Endicott J, Solomon D, Clayton P (2002) Can temperament identify affectively ill patients who engage in lethal or near-lethal suicidal behavior? A 14-year prospective study. Suicide Life Threat Behav 32:10–32

    Article  PubMed  Google Scholar 

  34. McGuffin P, Marusic A, Farmer A (2001) What can psychiatric genetics offer suicidology? Crisis 22:61–65

    Article  CAS  PubMed  Google Scholar 

  35. 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 236:160–185

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Joiner TE Jr, Brown JS, Wingate LR (2005) The psychology and neurobiology of suicidal behavior. Annu Rev Psychol 56:287–314

    Article  PubMed  Google Scholar 

  37. Antypa N, Serretti A, Rujescu D (2013) Serotonergic genes and suicide: a systematic review. Eur Neuropsychopharmacol 23:1125–1142

    Article  CAS  PubMed  Google Scholar 

  38. 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 157:609–614

    Article  CAS  PubMed  Google Scholar 

  39. 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, Moscicki EK, Oquendo MA, Pandey GN, Pearson J, Stanley B, Terwilliger J, Wenzel A (2009) Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry 65:556–563

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Rujescu D, Giegling I (2010) The genetics of neurosystems in mental ill-health and suicidality: beyond serotonin. Eur Psychiatry 25:272–274

    Article  CAS  PubMed  Google Scholar 

  41. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM (1996) Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 6:243–250

    Article  CAS  PubMed  Google Scholar 

  42. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mrna, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75:807–821

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Antypa N, Drago A, Serretti A (2013) The role of COMT gene variants in depression: bridging neuropsychological, behavioral and clinical phenotypes. Neurosci Biobehav Rev 37:1597–1610

    Article  CAS  PubMed  Google Scholar 

  44. Kia-Keating BM, Glatt SJ, Tsuang MT (2007) Meta-analyses suggest association between COMT, but not HTR1B, alleles, and suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 144B:1048–1053

    Article  PubMed  Google Scholar 

  45. Calati R, Porcelli S, Giegling I, Hartmann AM, Moller 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 45:309–321

    Article  PubMed  Google Scholar 

  46. De Luca V, Strauss J, Kennedy JL (2008) Power based association analysis (PBAT) of serotonergic and noradrenergic polymorphisms in bipolar patients with suicidal behaviour. Prog Neuropsychopharmacol Biol Psychiatry 32:197–203

    Article  PubMed  CAS  Google Scholar 

  47. Zalsman G, Huang YY, Oquendo MA, Brent DA, Giner L, Haghighi F, Burke AK, Ellis SP, Currier D, Mann JJ (2008) No association of COMT Val158Met polymorphism with suicidal behavior or CSF monoamine metabolites in mood disorders. Arch Suicide Res 12:327–335

    Article  PubMed Central  PubMed  Google Scholar 

  48. Schosser A, Calati R, Serretti A, Massat I, Kocabas NA, Papageorgiou K, Linotte S, Mendlewicz J, Souery D, Zohar J, Juven-Wetzler A, Montgomery S, Kasper S (2012) The impact of COMT gene polymorphisms on suicidality in treatment resistant major depressive disorder—a European multicenter study. Eur Neuropsychopharmacol 22:259–266

    Article  CAS  PubMed  Google Scholar 

  49. Golimbet VE, Alfimova MV, Gritsenko IK, Ebstein RP (2007) Relationship between dopamine system genes and extraversion and novelty seeking. Neurosci Behav Physiol 37:601–606

    Article  CAS  PubMed  Google Scholar 

  50. Hoth KF, Paul RH, Williams LM, Dobson-Stone C, Todd E, Schofield PR, Gunstad J, Cohen RA, Gordon E (2006) Associations between the COMT Val/Met polymorphism, early life stress, and personality among healthy adults. Neuropsychiatr Dis Treat 2:219–225

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Kulikova MA, Maluchenko NV, Timofeeva MA, Shlepzova VA, Schegolkova JV, Sysoeva OV, Ivanitsky AM, Tonevitsky AG (2008) Effect of functional catechol-O-methyltransferase Val158Met polymorphism on physical aggression. Bull Exp Biol Med 145:62–64

    Article  CAS  PubMed  Google Scholar 

  52. Rujescu D, Giegling I, Gietl A, Hartmann AM, Moller HJ (2003) A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits. Biol Psychiatry 54:34–39

    Article  CAS  PubMed  Google Scholar 

  53. Hong JP, Lee JS, Chung S, Jung J, Yoo HK, Chang SM, Kim CY (2008) New functional single nucleotide polymorphism (Ala72Ser) in the COMT gene is associated with aggressive behavior in male schizophrenia. Am J Med Genet B Neuropsychiatr Genet 147B:658–660

    Article  CAS  PubMed  Google Scholar 

  54. Soyka M (2011) Neurobiology of aggression and violence in schizophrenia. Schizophr Bull 37:913–920

    Article  PubMed Central  PubMed  Google Scholar 

  55. Dwivedi Y (2010) Brain-derived neurotrophic factor and suicide pathogenesis. Ann Med 42:87–96

    Article  PubMed Central  PubMed  Google Scholar 

  56. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:804–815

    Article  CAS  PubMed  Google Scholar 

  57. Sen S, Duman R, Sanacora G (2008) Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 64:527–532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Piccinni A, Marazziti D, Catena M, Domenici L, Del Debbio A, Bianchi C, Mannari C, Martini C, Da Pozzo E, Schiavi E, Mariotti A, Roncaglia I, Palla A, Consoli G, Giovannini L, Massimetti G, Dell’Osso L (2008) Plasma and serum brain-derived neurotrophic factor (BDNF) in depressed patients during 1 year of antidepressant treatments. J Affect Disord 105:279–283

    Article  CAS  PubMed  Google Scholar 

  59. 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 24:4401–4411

    Article  CAS  PubMed  Google Scholar 

  60. Liu L, Foroud T, Xuei X, Berrettini W, Byerley W, Coryell W, El-Mallakh R, Gershon ES, Kelsoe JR, Lawson WB, MacKinnon DF, McInnis M, McMahon FJ, Murphy DL, Rice J, Scheftner W, Zandi PP, Lohoff FW, Niculescu AB, Meyer ET, Edenberg HJ, Nurnberger JI Jr (2008) Evidence of association between brain-derived neurotrophic factor gene and bipolar disorder. Psychiatr Genet 18:267–274

    Article  PubMed Central  PubMed  Google Scholar 

  61. Lohoff FW, Sander T, Ferraro TN, Dahl JP, Gallinat J, Berrettini WH (2005) Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder. Am J Med Genet B Neuropsychiatr Genet 139B:51–53

    Article  CAS  PubMed  Google Scholar 

  62. Green EK, Raybould R, Macgregor S, Hyde S, Young AH, O’Donovan MC, Owen MJ, Kirov G, Jones L, Jones I, Craddock N (2006) Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder: case-control study of over 3000 individuals from the UK. Br J Psychiatry 188:21–25

    Article  PubMed  Google Scholar 

  63. Muller DJ, de Luca V, Sicard T, King N, Strauss J, Kennedy JL (2006) Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: family-based association study. Br J Psychiatry 189:317–323

    Article  PubMed  Google Scholar 

  64. Kim B, Kim CY, Hong JP, Kim SY, Lee C, Joo YH (2008) Brain-derived neurotrophic factor Val/Met polymorphism and bipolar disorder. Association of the met allele with suicidal behavior of bipolar patients. Neuropsychobiology 58:97–103

    Article  CAS  PubMed  Google Scholar 

  65. Zai CC, Manchia M, De Luca V, Tiwari AK, Chowdhury NI, Zai GC, Tong RP, Yilmaz Z, Shaikh SA, Strauss J, Kennedy JL (2012) The brain-derived neurotrophic factor gene in suicidal behaviour: a meta-analysis. Int J Neuropsychopharmacol 15:1037–1042

    Article  CAS  PubMed  Google Scholar 

  66. Sarchiapone M, Carli V, Roy A, Iacoviello L, Cuomo C, Latella MC, di Giannantonio M, Janiri L, de Gaetano M, Janal MN (2008) Association of polymorphism (Val66Met) of brain-derived neurotrophic factor with suicide attempts in depressed patients. Neuropsychobiology 57:139–145

    Article  CAS  PubMed  Google Scholar 

  67. Schenkel LC, Segal J, Becker JA, Manfro GG, Bianchin MM, Leistner-Segal S (2010) The BDNF Val66Met polymorphism is an independent risk factor for high lethality in suicide attempts of depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 34:940–944

    Article  CAS  PubMed  Google Scholar 

  68. Niitsu T, Fabbri C, Bentini F, Serretti A (2013) Pharmacogenetics in major depression: a comprehensive meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 45:183–194

    Article  CAS  PubMed  Google Scholar 

  69. Pae CU, Chiesa A, Porcelli S, Han C, Patkar AA, Lee SJ, Park MH, Serretti A, De Ronchi D (2012) Influence of BDNF variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia. Neuropsychobiology 65:1–11

    Article  CAS  PubMed  Google Scholar 

  70. Chen Z, Gibson TB, Robinson F, Silvestro L, Pearson G, Xu B, Wright A, Vanderbilt C, Cobb MH (2001) Map kinases. Chem Rev 101:2449–2476

    Article  CAS  PubMed  Google Scholar 

  71. Sweatt JD (2001) The neuronal map kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76:1–10

    Article  CAS  PubMed  Google Scholar 

  72. Bogoyevitch MA, Court NW (2004) Counting on mitogen-activated protein kinases—ERKs 3, 4, 5, 6, 7 and 8. Cell Signal 16:1345–1354

    Article  CAS  PubMed  Google Scholar 

  73. Dwivedi Y, Rizavi HS, Zhang H, Roberts RC, Conley RR, Pandey GN (2009) Aberrant extracellular signal-regulated kinase (ERK)1/2 signalling in suicide brain: role of ERK kinase 1 (MEK1). Int J Neuropsychopharmacol 12:1337–1354

    Article  CAS  PubMed  Google Scholar 

  74. Yuan P, Zhou R, Wang Y, Li X, Li J, Chen G, Guitart X, Manji HK (2010) Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophrenia. J Affect Disord 124:164–169

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Qi X, Lin W, Li J, Pan Y, Wang W (2006) The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress. Behav Brain Res 175:233–240

    Article  CAS  PubMed  Google Scholar 

  76. Qi X, Lin W, Li J, Li H, Wang W, Wang D, Sun M (2008) Fluoxetine increases the activity of the ERK-CREB signal system and alleviates the depressive-like behavior in rats exposed to chronic forced swim stress. Neurobiol Dis 31:278–285

    Article  CAS  PubMed  Google Scholar 

  77. Qi H, Mailliet F, Spedding M, Rocher C, Zhang X, Delagrange P, McEwen B, Jay TM, Svenningsson P (2009) Antidepressants reverse the attenuation of the neurotrophic MEK/MAPK cascade in frontal cortex by elevated platform stress; reversal of effects on LTP is associated with GluA1 phosphorylation. Neuropharmacology 56:37–46

    Article  CAS  PubMed  Google Scholar 

  78. Wang Z, Wang J, Li J, Wang X, Yao Y, Zhang X, Li C, Cheng Y, Ding G, Liu L, Ding Z (2011) MEK/ERKs signaling is essential for lithium-induced neurite outgrowth in N2a cells. Int J Dev Neurosci 29:415–422

    Article  CAS  PubMed  Google Scholar 

  79. Kim SH, Seo MS, Jeon WJ, Yu HS, Park HG, Jung GA, Lee HY, Kang UG, Kim YS (2008) Haloperidol regulates the phosphorylation level of the MEK-ERK-p90RSK signal pathway via protein phosphatase 2A in the rat frontal cortex. Int J Neuropsychopharmacol 11:509–517

    Article  CAS  PubMed  Google Scholar 

  80. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22:3251–3261

    CAS  PubMed  Google Scholar 

  81. **ng J, Ginty DD, Greenberg ME (1996) Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273:959–963

    Article  CAS  PubMed  Google Scholar 

  82. Drago A, Crisafulli C, Sidoti A, Serretti A (2011) The molecular interaction between the glutamatergic, noradrenergic, dopaminergic and serotoninergic systems informs a detailed genetic perspective on depressive phenotypes. Prog Neurobiol 94:418–460

    Article  CAS  PubMed  Google Scholar 

  83. Serretti A, Chiesa A, Calati R, Massat I, Linotte S, Kasper S, Lecrubier Y, Antonijevic I, Forray C, Snyder L, Bollen J, Zohar J, De Ronchi D, Souery D, Mendlewicz J (2011) A preliminary investigation of the influence of CREB1 gene on treatment resistance in major depression. J Affect Disord 128:56–63

    Article  CAS  PubMed  Google Scholar 

  84. Boer U, Cierny I, Krause D, Heinrich A, Lin H, Mayr G, Hiemke C, Knepel W (2008) Chronic lithium salt treatment reduces CRE/CREB-directed gene transcription and reverses its upregulation by chronic psychosocial stress in transgenic reporter gene mice. Neuropsychopharmacology 33:2407–2415

    Article  PubMed  CAS  Google Scholar 

  85. Dwivedi Y, Rao JS, Rizavi HS, Kotowski J, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:273–282

    Article  CAS  PubMed  Google Scholar 

  86. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Roberts RC, Conley RR (2007) Cyclic amp response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus. Int J Neuropsychopharmacol 10:621–629

    Article  CAS  PubMed  Google Scholar 

  87. Souery D, Zaninotto L, Calati R, Linotte S, Mendlewicz J, Sentissi O, Serretti A (2012) Depression across mood disorders: review and analysis in a clinical sample. Compr Psychiatry 53:24–38

    Article  PubMed  Google Scholar 

  88. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The mini-international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20):22–33 (quiz 34–57)

    PubMed  Google Scholar 

  89. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382–389

    Article  CAS  PubMed  Google Scholar 

  91. Young RC, Biggs JT, Ziegler VE, Meyer DA (1978) A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 133:429–435

    Article  CAS  PubMed  Google Scholar 

  92. Park S, Choi JW, Kyoung Yi K, Hong JP (2013) Suicide mortality and risk factors in the 12 months after discharge from psychiatric inpatient care in Korea: 1989–2006. Psychiatry Res 208:145–150

    Article  PubMed  Google Scholar 

  93. Wilkowska-Chmielewska J, Szelenberger W, Wojnar M (2013) Age-dependent symptomatology of depression in hospitalized patients and its implications for DSM-5. J Affect Disord 150:142–145

    Article  PubMed  Google Scholar 

  94. Oostervink F, Boomsma MM, Nolen WA, Board EA (2009) Bipolar disorder in the elderly; different effects of age and of age of onset. J Affect Disord 116:176–183

    Article  PubMed  Google Scholar 

  95. Angold A, Costello EJ, Erkanli A, Worthman CM (1999) Pubertal changes in hormone levels and depression in girls. Psychol Med 29:1043–1053

    Article  CAS  PubMed  Google Scholar 

  96. Angold A, Costello EJ (2006) Puberty and depression. Child Adolesc Psychiatr Clin N Am 15:919–937 (ix)

    Article  PubMed  Google Scholar 

  97. Clarke MC, Coughlan H, Harley M, Connor D, Power E, Lynch F, Fitzpatrick C, Cannon M (2014) The impact of adolescent cannabis use, mood disorder and lack of education on attempted suicide in young adulthood. World Psychiatry 13:322–323

    Article  PubMed Central  PubMed  Google Scholar 

  98. Ostacher MJ, Lebeau RT, Perlis RH, Nierenberg AA, Lund HG, Moshier SJ, Sachs GS, Simon NM (2009) Cigarette smoking is associated with suicidality in bipolar disorder. Bipolar Disord 11:766–771

    Article  PubMed Central  PubMed  Google Scholar 

  99. Seo HJ, Jung YE, Jeong S, Kim JB, Lee MS, Kim JM, Yim HW, Jun TY (2014) Personality traits associated with suicidal behaviors in patients with depression: the CRESCEND study. Compr Psychiatry 55(5):1085–1092

  100. Sareen J, Cox BJ, Afifi TO, de Graaf R, Asmundson GJ, ten Have M, Stein MB (2005) Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry 62:1249–1257

    Article  PubMed  Google Scholar 

  101. McElroy SL, Altshuler LL, Suppes T, Keck PE Jr, Frye MA, Denicoff KD, Nolen WA, Kupka RW, Leverich GS, Rochussen JR, Rush AJ, Post RM (2001) Axis i psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder. Am J Psychiatry 158:420–426

    Article  CAS  PubMed  Google Scholar 

  102. Bauer MS, Altshuler L, Evans DR, Beresford T, Williford WO, Hauger R, Team VACS (2005) Prevalence and distinct correlates of anxiety, substance, and combined comorbidity in a multi-site public sector sample with bipolar disorder. J Affect Disord 85:301–315

    Article  PubMed  Google Scholar 

  103. Cassano GB, Pini S, Saettoni M, Dell’Osso L (1999) Multiple anxiety disorder comorbidity in patients with mood spectrum disorders with psychotic features. Am J Psychiatry 156:474–476

    Article  CAS  PubMed  Google Scholar 

  104. Chen YW, Dilsaver SC (1995) Comorbidity of panic disorder in bipolar illness: evidence from the epidemiologic catchment area survey. Am J Psychiatry 152:280–282

    Article  CAS  PubMed  Google Scholar 

  105. Chen YW, Dilsaver SC (1995) Comorbidity for obsessive-compulsive disorder in bipolar and unipolar disorders. Psychiatry Res 59:57–64

    Article  CAS  PubMed  Google Scholar 

  106. Rao KN, Kulkarni RR, Begum S (2013) Comorbidity of psychiatric and personality disorders in first suicide attempters. Indian J Psychol Med 35:75–79

    Article  PubMed Central  PubMed  Google Scholar 

  107. Brent DA, Perper JA, Moritz G, Liotus L, Schweers J, Balach L, Roth C (1994) Familial risk factors for adolescent suicide: a case-control study. Acta Psychiatr Scand 89:52–58

    Article  CAS  PubMed  Google Scholar 

  108. Gould MS, Fisher P, Parides M, Flory M, Shaffer D (1996) Psychosocial risk factors of child and adolescent completed suicide. Arch Gen Psychiatry 53:1155–1162

    Article  CAS  PubMed  Google Scholar 

  109. Pawlak J, Dmitrzak-Weglarz M, Skibinska M, Szczepankiewicz A, Leszczynska-Rodziewicz A, Rajewska-Rager A, Zaremba D, Czerski P, Hauser J (2013) Suicide attempts and clinical risk factors in patients with bipolar and unipolar affective disorders. Gen Hosp Psychiatry 35:427–432

    Article  PubMed  Google Scholar 

  110. Tondo L, Lepri B, Baldessarini RJ (2007) Suicidal risks among 2826 sardinian major affective disorder patients. Acta Psychiatr Scand 116:419–428

    Article  CAS  PubMed  Google Scholar 

  111. Pompili M, Innamorati M, Raja M, Falcone I, Ducci G, Angeletti G, Lester D, Girardi P, Tatarelli R, De Pisa E (2008) Suicide risk in depression and bipolar disorder: do impulsiveness-aggressiveness and pharmacotherapy predict suicidal intent? Neuropsychiatr Dis Treat 4:247–255

    Article  PubMed Central  PubMed  Google Scholar 

  112. Kim YK, Lee HP, Won SD, Park EY, Lee HY, Lee BH, Lee SW, Yoon D, Han C, Kim DJ, Choi SH (2007) Low plasma BDNF is associated with suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry 31:78–85

    Article  CAS  PubMed  Google Scholar 

  113. 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 67:258–267

    Article  CAS  PubMed  Google Scholar 

  114. Hong CJ, Huo SJ, Yen FC, Tung CL, Pan GM, Tsai SJ (2003) Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior. Neuropsychobiology 48:186–189

    Article  CAS  PubMed  Google Scholar 

  115. Pregelj P, Nedic G, Paska AV, Zupanc T, Nikolac M, Balazic J, Tomori M, Komel R, Seler DM, Pivac N (2011) The association between brain-derived neurotrophic factor polymorphism (BDNF Val66Met) and suicide. J Affect Disord 128:287–290

    Article  CAS  PubMed  Google Scholar 

  116. Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN (2001) Reduced activation and expression of ERK1/2 map kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 77:916–928

    Article  CAS  PubMed  Google Scholar 

  117. Einat H, Manji HK, Gould TD, Du J, Chen G (2003) Possible involvement of the ERK signaling cascade in bipolar disorder: behavioral leads from the study of mutant mice. Drug News Perspect 16:453–463

    Article  CAS  PubMed  Google Scholar 

  118. Schild AH, Pietschnig J, Tran US, Voracek M (2013) Genetic association studies between SNPs and suicidal behavior: a meta-analytical field synopsis. Prog Neuropsychopharmacol Biol Psychiatry 46:36–42

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biomedical and NeuroMotor Sciences, Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy

    Mario Tomasini & Alessandro Serretti

  2. Department of Clinical Psychology, Institute of Psychology, Leiden University, Leiden, The Netherlands

    Niki Antypa

  3. Laboratoire de Psychologie Medicale, Centre Europe´en de Psychologie Medicale, Universite´ Libre de Bruxelles and Psy Pluriel, Brussels, Belgium

    Daniel Souery & Julien Mendlewicz

  4. Laboratory of Biology of Neurodegenerative DisordersNeuroscience Department, IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy

    Diego Albani & Federica Fusco

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  1. Niki Antypa
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  2. Daniel Souery
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  3. Mario Tomasini
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  4. Diego Albani
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Correspondence to Alessandro Serretti.

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Prof. Serretti is or has been consultant/speaker for: Abbott, Angelini, Astra Zeneca, Clinical Data, Boheringer, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Italfarmaco, Janssen, Lundbeck, Pfizer, Sanofi, Servier. Dr. Souery has received grant/research support from GlaxoSmithKline and Lundbeck and has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen and Lundbeck. Prof. Mendlewicz is a member of the Board of the Lundbeck International Neuroscience Foundation and of Advisory Board of Servier. The other authors report no conflict of interest.

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Antypa, N., Souery, D., Tomasini, M. et al. Clinical and genetic factors associated with suicide in mood disorder patients. Eur Arch Psychiatry Clin Neurosci 266, 181–193 (2016). https://doi.org/10.1007/s00406-015-0658-1

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