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Neurobiology of suicide: do biomarkers exist?

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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.

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Acknowledgments

This study was supported by the AXA Research Fund, SNF Grant 320030_132853.

Conflict of interest

Nader Perroud is on the advisory board for Lundbeck. The other authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland

    Alessandra Costanza, Isabella D’Orta & Nader Perroud

  2. Department of Psychiatry, University of Geneva, Hôpital de Belle-Idée, 2 ch. du Petit-Bel-Air, 1225, Chêne-Bourg, Switzerland

    Nader Perroud & Alain Malafosse

  3. Department of Medical Genetic and Laboratories, University Hospitals of Geneva, Geneva, Switzerland

    Alain Malafosse

  4. University Center of Legal Medicine, Lausanne–Geneva (CMU), 9, av. de Champel, CH-1211, Geneva 4, Switzerland

    Sandra Burkhardt, Patrice Mangin & Romano La Harpe

Authors
  1. Alessandra Costanza
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  2. Isabella D’Orta
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  3. Nader Perroud
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  4. Sandra Burkhardt
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  5. Alain Malafosse
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  6. Patrice Mangin
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  7. Romano La Harpe
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Corresponding author

Correspondence to Nader Perroud.

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Glossary

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 %.

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Costanza, A., D’Orta, I., Perroud, N. et al. Neurobiology of suicide: do biomarkers exist?. Int J Legal Med 128, 73–82 (2014). https://doi.org/10.1007/s00414-013-0835-6

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  • DOI: https://doi.org/10.1007/s00414-013-0835-6

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