nach oben

Erschienen in:

01.01.2014 | Review Article

Neurobiology of suicide: do biomarkers exist?

verfasst von: Alessandra Costanza, Isabella D’Orta, Nader Perroud, Sandra Burkhardt, Alain Malafosse, Patrice Mangin, Romano La Harpe

Erschienen in: International Journal of Legal Medicine | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Clinical risk factors have a low predictive value on suicide. This may explain the increasing interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. This review aims to present the current neurobiological findings that have been shown to be implicated in suicide completers and to discuss how postmortem studies may be useful in characterizing these individuals. Data on the role of the main neurobiological systems in suicidality, such as the neurotransmitter families, hypothalamic–pituitary–adrenal axis, neurotrophic factors, and polyamines, are exposed at the different biochemical, genetic, and epigenetic levels. Some neuroanatomic and neuropathological aspects as well as their in vivo morphological and functional neuroimaging correlates are also described. Except for the serotoninergic system, particularly with respect to the polymorphism of the gene coding for the serotonin transporter (5-HTTLPR) and brain-derived neurotrophic factor, data did not converge to produce a univocal consensus. The possible limitations of currently published studies are discussed, as well as the scope for long-term prospective studies.

Nur mit Berechtigung zugänglich

Allele

one of the different forms of a gene that can exist at a single gene locus.

Association mapping

a method used for direct identification of the specific genes (see candidate gene) that control the differences in phenotype among members of a population.

Candidate gene

a gene that, because of its chromosomal position or another property, becomes a candidate for a particular function such as disease risk.

DNA methylation

the addition of methyl groups to DNA residues after replication; it is a mechanism of gene transcription regulation. It represents an important heritable epigenetic mark (see epigenetic).

Endophenotype

quantifiable biologic or psychological variable associated with genetic risk for a disorder; also named intermediate phenotype.

Epigenetic

nongenetic chemical changes in histones or DNA which alter gene function without altering the DNA sequence.

Exome sequencing

sequencing of a set of expressed regions of genes (exons). It is performed only for rare SNPs.

Gene locus

the specific place on a chromosome where a gene is located.

Genome-wide association

association mapping that uses marker genes loci to scan the entire genome for genes contributing to quantitative variation. It does not require an a priori hypothesis on candidate genes.

Haplotype

the combination of alleles at multiple gene loci on the same segment of homologous chromosomes.

Microarray study

analysis of an array of DNA fragments representing all the genes in a genome. This technique simultaneously examines the expression levels of thousands of gene transcripts.

microRNA (miRNAs)

a class of functional RNA that regulates the amount of protein produced by a gene; it represents a mechanism of gene expression regulation (post-transcriptional gene repression).

Phenotype

(1) The form taken by some character (or group of characters) in a specific individual. (2) The detectable outward manifestations of a specific genotype.

Polymorphism

the coexistence of two or more common phenotypes of a character.

Single-nucleotide polymorphisms (SNPs or SNIP)

a nucleotide pair difference at a given location in the genomes of two or more individuals. They represent the most prevalent types of polymorphisms. Common SNPs: when the less common allele occurs at a frequency of about 5 % or greater; rare SNPs: when the less common allele occurs at a frequency below 5 %.

Krug EG, Mercy JA, Dahlberg LL, Zwi AB (2002) The world report on violence and health. Lancet 360:1083–1088PubMedCrossRef

Turecki G, Ernst C, Jollant F, Labonté B, Mechawar N (2012) The neurodevelopmental origins of suicidal behavior. Trends Neurosci 35:14–23PubMedCrossRef

Hawton K, van Heeringen K (2009) Suicide. Lancet 373:1372–1381PubMedCrossRef

Brezo J, Paris J, Vitaro F, Hébert M, Tremblay RE, Turecki G (2008) Predicting suicide attempts in young adults with histories of childhood abuse. Br J Psychiatry 193:134–139PubMedCrossRef

Qin P, Agerbo E, Bo Mortensen PB (2003) Suicide risk in relation to socioeconomic, demographic, psychiatric, and familial factors: a national register-based study of all suicides in Denmark, 1981–1997. Am J Psychiatry 160:765–772PubMedCrossRef

Mann JJ (2003) Neurobiology of suicidal behavior. Nat Rev Neurosci 4:819–828PubMedCrossRef

Ernst C, Mechawar N, Turecki G (2009) Suicide neurobiology. Prog Neurobiol 89:315–333PubMedCrossRef

Klempan TA, Sequeira A, Canetti L, Lalovic A, Ernst C, ffrench-Mullen J, Turecki G (2009) Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression. Mol Psychiatry 14:175–189PubMedCrossRef

Fiori LM, Turecki G (2010) Gene expression profiling of suicide completers. Eur Psychiatry 25:287–290PubMedCrossRef

10.

Sequeira A, Morgan L, Walsh DM, Cartagena PM, Choudary P, Li J, Schatzberg AF, Watson SJ, Akil H, Myers RM, Jones EG, Bunney WE, Vaeter MP (2012) Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide. PLoS One 7:e35367PubMedCentralPubMedCrossRef

11.

Bondy B, Buettner A, Zill P (2006) Genetics of suicide. Mol Psychiatry 11:336–351PubMedCrossRef

12.

Leboyer M, Slama F, Siever BF (2005) Suicidal disorders: a nosological entity per se? Am J Med Genet C Semin Med Genet 133C:3–7PubMedCrossRef

13.

Perroud N, Neidhart E, Petit B, Vessaz M, Laforge T, Relecom C, La Harpe R, Malafosse A, Guipponi M (2010) Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2 gene expression in the ventral prefrontal cortex of suicide victims. Am J Med Genet Part B 153B:909–918PubMedCrossRef

14.

Bondy B, Erfurth A, de Jonge S, Krüger M, Meyer H (2000) Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide. Mol Psychiatry 5:193–195PubMedCrossRef

15.

Zalsman G, Molcho A, Huang Y, Dwork A, Li S, Mann JJ (2005) Postmortem mu-opioid receptor binding in suicide victims and controls. J Neural Transm 112:949–954PubMedCrossRef

16.

Coryell W, Schlesser M (2001) The dexamethasone suppression test and suicide prediction. Am J Psychiatry 158:748–753PubMedCrossRef

17.

Perroud N, Paoloni-Giacobino A, Prada P, Olié E, Salzmann A, Nicastro R, Guillaume S, Mouthon D, Stouder C, Dieben K, Huguelet P, Courtet P, Malafosse A (2011) 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. doi:10.1038/tp.2011.60

18.

McGowan PO, Sasaki A, D’Alessio A, Dymov S, Labonté B, Szyf M, Turecki G, Meaney MJ (2009) Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 12:342–348PubMedCentralPubMedCrossRef

19.

Labonté B, Yerko V, Gross J, Mechawar N, Meaney MJ, Szyf M, Turecki G (2012) Differential glucocorticoid receptor exon 1_B, 1_C, and 1_H expression and methylation in suicide completers with a history of childhood abuse. Biol Psychiatry. doi:10.1016/j.biopsych.2012.01.034

20.

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 67:258–267PubMedCrossRef

21.

Karege F, Perroud N, Burkhardt S, Fernandez R, Ballmann E, La Harpe R, Malafosse A (2011) Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims. Neuropsychobiology 63:224–231PubMedCrossRef

22.

Zhang L, Su TP, Choi K, Maree W, Li CT, Chung MY, Chen YS, Bai YM, Chou YH, Barker JL, Barrett JE, Li XX, Li H, Benedek DM, Ursano R (2011) P11 (S100A10) as a potential biomarker of psychiatric patients at risk of suicide. J Psychiatr Res 45:435–441PubMedCrossRef

23.

Pandey GN, Dwivedi Y (2010) What can post-mortem studies tell us about the pathoetiology of suicide? Future Neurol 5:701–720PubMedCentralPubMedCrossRef

24.

Fiori LM, Turecki G (2010) Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers. Int J Neuropsychopharmacol 13:725–736PubMedCrossRef

25.

Torres-Platas SG, Hercher C, Davoli MA, Maussion G, Labonté B, Turecki G, Mechawar N (2011) Astrocytic hypertrophy in anterior cingulated white matter of depressed suicides. Neuropsychopharmachology 36:2650–2658CrossRef

26.

Ernst C, Nagy C, Kim S, Yang JP, Deng X, Hellstrom IC, Choi KH, Gershenfeld H, Meaney MJ, Turecki G (2011) Dysfunction of astrocyte connexins 30 and 43 in dorsal lateral prefrontal cortex of suicide completers. Biol Psychiatry 70:312–319PubMedCrossRef

27.

Underwood MD, Arango V (2011) Evidence for neurodegeneration and neuroplasticity as part of the neurobiology of suicide. Biol Psychiatry 70:306–307PubMedCrossRef

28.

Jollant F, Lawrence NL, Olié E, Guillaume S, Courtet P (2011) The suicidal mind and brain: a review of neuropsychological and neuroimaging studies. World J Biol Psychiatry 12:319–339PubMedCrossRef

29.

Courtet P, Gottesman II, Jollant F, Gould TD (2011) The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies? Transl Psychiatry 1(5):e7. doi:10.1038/tp.2011.6

30.

Turecki G (2005) Dissecting the suicide phenotype: the role of impulsive-aggressive behaviors. J Psychiatry Neurosci 30:398–408PubMedCentralPubMed

Titel: Neurobiology of suicide: do biomarkers exist?
verfasst von: Alessandra Costanza
Isabella D’Orta
Nader Perroud
Sandra Burkhardt
Alain Malafosse
Patrice Mangin
Romano La Harpe
Publikationsdatum: 01.01.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: International Journal of Legal Medicine / Ausgabe 1/2014
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-013-0835-6

Neu im Fachgebiet Rechtsmedizin

01.04.2024 | Forensische Traumatologie | CME

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Neurobiology of suicide: do biomarkers exist?

Abstract

Neu im Fachgebiet Rechtsmedizin

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2014

Does cone beam CT actually ameliorate stab wound analysis in bone?

Comparison of southern Chinese Han and Brazilian Caucasian mutation rates at autosomal short tandem repeat loci used in human forensic genetics

Driving under the influence of synthetic cannabinoids (“Spice”): a case series

Population data for 30 insertion–deletion markers in a Korean population

Body fluid identification by integrated analysis of DNA methylation and body fluid-specific microbial DNA

Validity and reliability of dental age estimation of teeth root translucency based on digital luminance determination

Neu im Fachgebiet Rechtsmedizin

Theoretische Grundlagen von Explosionen und Explosionsverletzungen

Auswirkungen vorgeschalteter Laborprozesse auf die Digitalisierung histologischer Schnittpräparate

Knochenmarkhistologie bei Zytopenien

Herausforderungen der Automation bei der quantitativen Auswertung von Leberbiopsien