Download PDF
Nervenheilkunde 2017; 36(04): 233-238
DOI: 10.1055/s-0038-1627008
Suizid
Schattauer GmbH

Aspekte der Genetik, Epigenetik und Gen-Umwelt-Interaktion bei suizidalem Verhalten

Aspects of genetics, epigenetics and gene environment interaction in suicidal behavior
I. Giegling
1   Klinik und Poliklinik für Psychiatrie, Psychotherapie und Psychosomatik der Martin-Luther-Universität Halle-Wittenberg
,
D. Rujescu
1   Klinik und Poliklinik für Psychiatrie, Psychotherapie und Psychosomatik der Martin-Luther-Universität Halle-Wittenberg
› Author Affiliations
Further Information

Publication History

eingegangen am: 04 October 2016

angenommen am: 30 November 2016

Publication Date:
20 January 2018 (online)

    Permissions and Reprints

Zusammenfassung

Suizidalem Verhalten liegt ein komplexes Zusammenspiel von vielen Faktoren zugrunde. Es wirken unterschiedliche Risiken zusammen, wie psychiatrische Erkrankungen, Persönlichkeitsparameter (z. B. Aggression, Impulsivität, Neurotizismus), schwere Kindheitstraumata, chronische Erkrankungen, soziale Faktoren (z. B. Arbeitslosigkeit, fehlendes soziales Netz, traumatische Lebensereignisse), kognitive Flexibilität sowie neurobiologische und genetische Faktoren. Dabei fungieren die letzteren im Sinne prädisponierender Risikofaktoren in Wechselwirkung mit Umweltfaktoren. Im Folgenden sollen die konsistentesten genetischen Befunde zusammengefasst werden. Insbesondere wird auf die familiäre Häufung suizidalen Verhaltens sowie auf die geschätzte Heritabilität von ca. 40–55% eingegangen. Darüber hinaus werden Kandidatengenstudien insbesondere aus dem Feld des serotonergen Systems vorgestellt, neuere genomweite Assoziationsstudien diskutiert sowie Gen-Umwelt-Analysen und epigenetische Ansätze beleuchtet.

Summary

Suicidal behavior is based on a complex interaction of many different factors. There are different risks, such as psychiatric disorders, personality traits (e.g. aggression, impulsiveness, neuroticism), severe childhood traumas, chronic illnesses, social factors (e.g. unemployment, lack of a social network, traumatic life events), cognitive flexibility, as well as neurobiological and genetic factors. The latter of which act in the sense of predisposing risk factors in interaction with environmental factors. In the following, the most consistent genetic findings are summarized below. In particular, the familial accumulation of suicidal behavior as well as the estimated heritability of about 40–55% are discussed. Furthermore, candidate gene studies are presented especially from the field of the serotonergic system, recent genome-wide association studies are discussed as well as gene environment analyzes and epigenetic approaches are pointed out.

Schlüsselwörter

Suizidalität - Genetik - Gen - Serotonin - GenUmwelt-Analyse - Epigenetik

Keywords

Suicidality - genetics - gene - serotonin - gene environment analysis - epigenetic
 

  • Literatur

  • 1 Antypa N, Serretti A, Rujescu D. Serotonergic genes and suicide: a systematic review. Eur Neuropsychopharmacol 2013; 23: 1125-42.
    CrossrefPubMedGoogle Scholar
  • 2 Antypa N. et al. MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls. Eur Arch Psychiatry Clin Neurosci 2013; 263: 393-403.
    CrossrefPubMedGoogle Scholar
  • 3 Barzman D, Geise C, Lin PI. Review of the genetic basis of emotion dysregulation in children and adolescents. World J Psychiatry 2015; 05: 112-7.
    Google Scholar
  • 4 Bellivier F, Chaste P, Malafosse A. Association between the TPH gene A218C polymorphism and suicidal behavior: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2004; 124B: 87-91.
    CrossrefPubMedGoogle Scholar
  • 5 Breen ME, Seifuddin F, Zandi PP, Potash JB, Willour VL. Investigating the role of early childhood abuse and HPA axis genes in suicide attempters with bipolar disorder. Psychiatr Genet 2015; 25 (03) 106-11.
    CrossrefPubMedGoogle Scholar
  • 6 Bronisch T. et al. A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results. Arch Suicide 2015; Res 09: 19-26.
    Google Scholar
  • 7 Brunner HG. et al. X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Hum Genet 1993; 52: 1032-39.
    PubMedGoogle Scholar
  • 8 Butler AW. et al. A genomewide linkage study on suicidality in major depressive disorder con?rms evidence for linkage to 2p12. Am J Med Genet Part B 2010; 153B: 1465-73.
    CrossrefPubMedGoogle Scholar
  • 9 Cao L, Li T, Xu K, Liu X. Association analysis of attempted suicide and 5-HT2A receptor gene. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2001; 18: 195-7.
    PubMedGoogle Scholar
  • 10 Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R. Role of genotype in the cycle of violence in maltreated children. Science 2002; 297: 851-854.
    CrossrefPubMedGoogle Scholar
  • 11 Caspi A. et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386-9.
    CrossrefPubMedGoogle Scholar
  • 12 Choong MY, Tee SF, Tang PY. Meta-analysis of polymorphisms in TPH2 gene and suicidal behavior. Psychiatry Res 2014; 220: 1163-6.
    CrossrefPubMedGoogle Scholar
  • 13 Clayden RC, Zaruk A, Meyre D, Thabane L, Samaan Z. 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 2012; 02: e166.
    CrossrefPubMedGoogle Scholar
  • 14 De la Cruz-Cano E. Association between FKBP5 and CRHR1 genes with suicidal behavior: A systematic review. Behav Brain Res 2016; 317: 46-61.
    PubMedGoogle Scholar
  • 15 De Medeiros Alves V, Bezerra DG, de Andrade TG, de Melo Neto VL, Nardi AE. Genetic Polymorphisms Might Predict Suicide Attempts in Mental Disorder Patients: A Systematic Review And Meta-Analysis. CNS Neurol Disord Drug Targets 2015; 14 (07) 820-7.
    CrossrefPubMedGoogle Scholar
  • 16 Dick DM. et al. Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts. Am J Med Genet B Neuropsychiatr Genet 2010; 153B (06) 1179-88.
    Google Scholar
  • 17 Du L, Bakish D, Lapierre YD, Ravindran AV, Hrdina PD. Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet 2000; 96: 56-60.
    CrossrefPubMedGoogle Scholar
  • 18 Erlangsen A, Fedyszyn I. Danish nationwide registers for public health and health-related research. Scand J Public Health 2015; 43: 333-9.
    CrossrefPubMedGoogle Scholar
  • 19 Esquirol JE. Des maladies mentales [deutsch: Die Geisteskrankheiten in Beziehung zur Medizin und Staatsarzneikunde. Berlin: Voß (2 Bände)]; Paris: Tircher 1838
    Google Scholar
  • 20 Galfalvy H. et al. A genome-wide association study of suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 2015; 168 (07) 557-63.
    CrossrefPubMedGoogle Scholar
  • 21 Giegling I, Hartmann AM, Moller HJ, Rujescu D. Angerand aggression-related traits are associated with polymorphisms in the 5-HT-2A gene. J Affect Disord 2006; 96: 75-81.
    CrossrefPubMedGoogle Scholar
  • 22 Giegling I, Moreno-De-Luca D, Calati R, Hartmann AM, Möller HJ, De Ronchi D, Rujescu D, Serretti A. Tyrosine hydroxylase and DOPA decarboxylase gene variants in personality traits. Neuropsychobiology 2009; 59: 23-7.
    CrossrefPubMedGoogle Scholar
  • 23 González-Castro TB, Juárez-Rojop I, López-Narváez ML, Tovilla-Zárate CA. Association of TPH-1 and TPH-2 gene polymorphisms with suicidal behavior: a systematic review and meta-analysis. BMC Psychiatry 2014; 14: 196.
    CrossrefPubMedGoogle Scholar
  • 24 Hesselbrock V. et al. The search for genetic risk factors associated with suicidal behavior. Alcohol Clin Exp Res 2004; 28: 70S-76S.
    CrossrefPubMedGoogle Scholar
  • 25 Hung CF. et al. Monoamine oxidase A gene polymorphism and suicide: an association study and meta-analysis. J Affect Disord 2012; 136: 643-9.
    CrossrefPubMedGoogle Scholar
  • 26 Kang HJ. et al. BDNF promoter methylation and suicidal behavior in depressive patients. J Affect Disord 2013; 151 (02) 679-85.
    CrossrefPubMedGoogle Scholar
  • 27 Kim JM. et al. BDNF promoter methylation associated with suicidal ideation in patients with breast cancer. Int J Psychiatry Med 2015; 49 (01) 75-94.
    CrossrefPubMedGoogle Scholar
  • 28 Klengel T. et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 2013; 16 (01) 33-41.
    CrossrefPubMedGoogle Scholar
  • 29 Laje G. et al. Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients. Pharmacogenet Genomics 2009; 19: 666-74.
    CrossrefPubMedGoogle Scholar
  • 30 Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527-31.
    CrossrefPubMedGoogle Scholar
  • 31 Li D, He L. Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia. Hum Genet 2006; 120: 22-30.
    CrossrefPubMedGoogle Scholar
  • 32 Mandelli L, Serretti A. Gene environment interaction studies in depression and suicidal behavior: An update. Neurosci Biobehav Rev 2013; 37: 2375-97.
    CrossrefPubMedGoogle Scholar
  • 33 Mann JJ, Stanley M, McBride PA, McEwen BS. Increased serotonin and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 1986; 43: 954-9.
    CrossrefPubMedGoogle Scholar
  • 34 Menke A. et al. Genome-wide association study of antidepressant treatment-emergent suicidal ideation. Neuropsychopharmacol 2012; 37: 797-807.
    CrossrefPubMedGoogle Scholar
  • 35 Mittendorfer-Rutz E, Rasmussen F, Wasserman D. Familial clustering of suicidal behaviour and psychopathology in young suicide attempters. A register-based nested case control study. Soc Psychiatry Psychiatr Epidemiol 2008; 43: 28-36.
    CrossrefPubMedGoogle Scholar
  • 36 Mullins N. et al. Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study. Am J Med Genet B Neuropsychiatr Genet 2014; 165B: 428-37.
    Google Scholar
  • 37 New AS, Gelernter J, Goodman M, Mitropoulou V, Koenigsberg H, Silverman J, Siever LJ. Suicide, impulsive aggression, and HTR1B genotype. Biol Psychiatry 2001; 50: 62-5.
    CrossrefPubMedGoogle Scholar
  • 38 Nock MK. et al. Cross-national analysis of the associations among mental disorders and suicidal behavior: findings from the WHO World Mental Health Surveys. PLoS Med 2009; 06: 1-17.
    CrossrefPubMedGoogle Scholar
  • 39 Pawlak J. et al. Suicide behavior as a quantitative trait and its genetic background. J Affect Disord 2016; 206: 241-50.
    CrossrefPubMedGoogle Scholar
  • 40 Perlis RH. et al. Genome-wide association study of suicide attempts in mood disorder patients. Am J Psychiatry 2010; 167: 1499-507.
    CrossrefPubMedGoogle Scholar
  • 41 Perroud N. et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry 2011; 01 (12) e59.
    CrossrefPubMedGoogle Scholar
  • 42 Perroud N. et al. Genome-wide association study of increasing suicidal ideation during antidepressant treatment in the GENDEP project. Pharmacogenomics J 2012; 12: 68-77.
    CrossrefPubMedGoogle Scholar
  • 43 Qin P, Agerbo E, Mortensen PB. Suicide risk in relation to family history of completed suicide and psychiatric disorders: a nested case-control study based on longitudinal registers. Lancet 2002; 360: 1126-30.
    CrossrefPubMedGoogle Scholar
  • 44 Roy A, Segal NL, Centerwall BS, Robinette CD. Suicide in twins. Arch Gen Psychiatry 1991; 48: 29-32.
    CrossrefPubMedGoogle Scholar
  • 45 Roy A, Gorodetsky E, Yuan Q, Goldman D, Enoch MA. Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacol 2010; 35: 1674-83.
    CrossrefPubMedGoogle Scholar
  • 46 Roy A, Hodgkinson CA, Deluca V, Goldman D, Enoch MA. Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. J Psychiatr Res 2012; 46: 72-9.
    CrossrefPubMedGoogle Scholar
  • 47 Rujescu D, Giegling I, Sato T, Hartmann AM, Möller HJ. Genetic variations in tryptophan hydroxylase in suicidal behavior: analysis and metaanalysis. Biol Psychiatry 2003; 54: 465-73.
    CrossrefPubMedGoogle Scholar
  • 48 Rujescu D, Giegling I, Sato T, Möller HJ. Lack of association between serotonin 5-HT1B receptor gene polymorphism and suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 2003; 116B: 69-71.
    CrossrefPubMedGoogle Scholar
  • 49 Sadkowski M, Dennis B, Clayden RC, Elsheikh W, Rangarajan S, Dejesus J, Samaan Z. The role of the serotonergic system in suicidal behavior. Neuropsychiatr Dis Treat 2013; 09: 1699-716.
    Google Scholar
  • 50 Schild AH, Pietschnig J, Tran US, Voracek M. Genetic association studies between SNPs and suicidal behavior: a meta-analytical field synopsis. Prog Neuropsychopharmacol Biol Psychiatry 2013; 46: 36-42.
    CrossrefPubMedGoogle Scholar
  • 51 Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014; 511: 421-7.
    CrossrefPubMedGoogle Scholar
  • 52 Schosser A. et al. Genomewide association scan of suicidal thoughts and behaviour in major depression. PLoS One 2011; 6e20690.
    Google Scholar
  • 53 Schulsinger F. A family study of suicide. In: Schov M, Stromgren G. Origin, Prevention and Treatment of Affective Disorders. New York: Academic Press; 1979: 277-87.
    Google Scholar
  • 54 Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1983; 01: 214-6.
    Google Scholar
  • 55 Statham DJ, Heath AC, Madden PA, Bucholz KK, Bierut L, Dinwiddie SH, Slutske WS, Dunne MP, Martin NG. Suicidal behaviour: an epidemiological and genetic study. Psychol Med 1998; 28: 839-55.
    CrossrefPubMedGoogle Scholar
  • 56 Thornton LM, Welch E, Munn-Chernoff MA, Lichtenstein P, Bulik CM. Anorexia nervosa, major depression, and suicide attempts: Shared genetic factors. Suicide Life Threat Behav 2016; 46 (05) 525-34.
    CrossrefPubMedGoogle Scholar
  • 57 Tovilla-Zárate C. et al. No association between COMT val158met polymorphism and suicidal behavior: meta-analysis and new data. BMC Psychiatry 2011; 11: 151.
    CrossrefPubMedGoogle Scholar
  • 58 Tsai SJ, Hong CJ, Liou YJ. Recent molecular genetic studies and methodological issues in suicide research. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 809-17.
    CrossrefPubMedGoogle Scholar
  • 59 Tyrka AR, Ridout KK, Parade SH, Paquette A, Marsit CJ, Seifer R. Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5). Dev Psychopathol 2015; 27 (02) 1637-45.
    CrossrefPubMedGoogle Scholar
  • 60 Von Borczyskowski A, Lindblad F, Vinnerljung B, Reintjes R, Hjern A. Familial factors and suicide: an adoption study in a Swedish National Cohort. Psychol Med 2011; 41: 749-58.
    CrossrefPubMedGoogle Scholar
  • 61 Voracek M, Loibl LM. Genetics of suicide: a systematic review of twin studies. Wien Klin Wochenschr 2007; 119: 463-75.
    CrossrefPubMedGoogle Scholar
  • 62 Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H, Bader M. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 2003; 299: 76.
    CrossrefPubMedGoogle Scholar
  • 63 Wang JY, Jia CX, Lian Y, Sun SH, Lyu M, Wu A. Association of the HTR2A 102T/C polymorphism with attempted suicide: a meta-analysis. Psychiatr Genet 2015; 25: 168-77.
    CrossrefPubMedGoogle Scholar
  • 64 Wasserman D, Rihmer Z, Rujescu D, Sarchiapone M, Sokolowski M, Titelman D, Zalsman G, Zemishlany Z, Carli V. European Psychiatric Association. The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. Eur Psychiatry 2012; 27: 129-41.
    CrossrefPubMedGoogle Scholar
  • 65 Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, Dymov S, Szyf M, Meaney MJ. Epigenetic programming by maternal behavior. Nat Neurosci 2004; 07 (08) 847-54.
    CrossrefPubMedGoogle Scholar
  • 66 Wender PH, Kety SS, Rosenthal D, Schulsinger F, Ortmann J, Lunde I. Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Arch Gen Psychiatry 1986; 43: 923-9.
    CrossrefPubMedGoogle Scholar
  • 67 Willour VL. et al. A genome-wide association study of attempted suicide. Mol Psychiatry 2012; 17: 433-44.
    CrossrefPubMedGoogle Scholar
  • 68 Zai CC. et al. The brain-derived neurotrophic factor gene in suicidal behaviour: a meta-analysis. Int J Neuropsychopharmacol 2012; 15: 1037-42.
    CrossrefPubMedGoogle Scholar
  • 69 Zai CC. et al. A genome-wide association study of suicide severity scores in bipolar disorder. J Psychiatr Res 2015; 65: 23-9.
    CrossrefPubMedGoogle Scholar
  • 70 Zhang HY, Ishigaki T, Tani K, Chen K, Shih JC, Miyasato K, Ohara K, Ohara K. Serotonin2A receptor gene polymorphism in mood disorders. Biol Psychiatry 1997; 41: 768-73.
    CrossrefPubMedGoogle Scholar
  • 71 Zill P, Buttner A, Eisenmenger W, Moller HJ, Bondy B, Ackenheil M. Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims. Biol Psychiatry 2004; 56: 581-6.
    CrossrefPubMedGoogle Scholar
  • 72 Zubenko GS, Maher BS, Hughes III HB, Zubenko WN, Scott SJ, Marazita ML. 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 2004; 129B: 47-54.
    CrossrefPubMedGoogle Scholar