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Neurobiology of suicidal behaviour

Key Points

  • Suicidal behaviour refers to the occurrence of self-directed injurious acts with intent to end one's own life. Suicide is not simply a response to stress, but is a complication of an existing psychiatric disorder.

  • Many models of suicidal behaviour have been put forward. This article presents a stress–diathesis model in which a stressor leads to the acute worsening of a psychiatric disorder, leading to suicidal behaviour. Many factors are components of the diathesis for suicidal behaviour. They include pessimism, aggression, impulsivity, familial/genetic factors and childhood experiences.

  • Most of the neurochemical evidence, particularly evidence obtained from the brains of suicide victims, points to the involvement of the serotonergic system in suicidal behaviour. The noradrenergic and dopaminergic systems have also been implicated, but the evidence is more fragmentary.

  • As a result of the neurochemical observations, the genetic study of suicidal behaviour has centred on the study of genes that govern the function of the serotonergic system. Although different polymorphisms in the genes that encode tryptophan hydroxylase, the serotonin transporter, the different serotonin receptors and monoamine oxidase have been found, their relationship to suicidal behaviour remains unclear.

  • Neuroanatomically, people who display suicidal behaviour tend to show abnormalities in the ventromedial prefrontal cortex. These abnormalities largely correlate with the neurochemical deficits that have been reported in this population.

  • The diathesis of suicidal behaviour offers new therapeutic possibilities. However, these are still early days in the study of suicide, and it will be important to identify additional markers (genetic, anatomical and neuropsychological) for identifying people at risk of showing suicidal behaviour.

Abstract

About one million suicides and ten million suicide attempts occur worldwide each year. Suicide is not simply a response to stress, but generally a complication of a psychiatric disorder. A proposed stress–diathesis model is described in clinical and neurobiological terms. Neurobiological correlates of the diathesis for suicidal acts point to the involvement of the serotonergic and noradrenergic systems, and the ventromedial prefrontal cortex. Some treatments seem to reduce suicide risk independently of an effect on the primary psychiatric disorder, perhaps by reducing the diathesis.

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Figure 1: Effects of genetics, head injury and childhood abuse on mood disorders and impulsivity in relation to suicidal behaviour.
Figure 2: A stress–diathesis model of suicidal behaviour.
Figure 3: Serotonin and suicidal behaviour.
Figure 4: Serotonin and suicidal behaviour.
Figure 5: Stress sensitivity and hopelessness.
Figure 6: Differences in anterior cingulate and lateral prefrontal cortex brain activity after serotonin release related to suicide attempt behaviour.

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Acknowledgements

Thanks to V. Arango, M. Underwood, D. Brent and M. Oquendo for ideas and suggestions. Supported by grants from the National Institute of Mental Health.

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5-HT1A

5-HT2A

HTR1A

HTR1B

HTR2A

MAOA

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TPH2

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Glossary

BORDERLINE PERSONALITY DISORDER

According to the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), this is a pervasive pattern of instability of interpersonal relationships, self-image, affects and marked impulsivity, which begins by early adulthood and is present in various contexts.

ANTISOCIAL PERSONALITY DISORDER

According to the DSM-IV, this is a pervasive pattern of disregard for and violation of the rights of others, occurring from the age of 15 years.

DIATHESIS

In the medical literature, it is a constitution of the body that makes it react in specific ways to extrinsic stimuli, thereby tending to make the person more susceptible than normal to certain diseases.

STATINS

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A, which are commonly used to reduce the amount of low-density lipoprotein cholesterol.

PSYCHOLOGICAL AUTOPSY

Interviews with friends and next-of-kin of a subject who committed suicide, trying to establish the reasons for suicidal behaviour.

AUTORADIOGRAPHIC STUDIES

Technique in which a specimen that has been labelled with a radioactive molecule (usually the ligand of a receptor) is placed on a photographic emulsion. Its subsequent development reveals the localization of radioactivity, and therefore the localization of the molecule of interest, as a pattern of silver grains.

BRODMANN AREAS

Korbinian Brodmann (1868–1918) was an anatomist who divided the cerebral cortex into numbered subdivisions on the basis of cell arrangements, types and staining properties. Modern derivatives of his maps are commonly used as the reference system for discussion of brain-imaging findings.

CONCORDANCE

The occurrence of a trait in two related individuals, such as twins or siblings.

HERITABILITY

The proportion of variability in a particular characteristic that can be attributed to genetic influences. This is a statistical description that applies to a specific population and might change if the environment is altered.

POLYMORPHISM

The simultaneous existence in the same population of two or more genotypes in frequencies that cannot be explained by recurrent mutations.

LINKAGE DISEQUILIBRIUM

A condition in which the frequency of a particular haplotype for two loci is significantly greater than that expected from the product of the observed allelic frequencies at each locus.

ENDOPHENOTYPES

The physiological traits that are related to a disease; for example, blood pressure, angiotensin levels or salt sensitivity are endophenotypes of hypertension.

ANISOTROPY

When the physical properties of a given medium have different values, when measured along axes orientated in different directions, it is said to be anisotropic.

REVERSAL LEARNING

A situation in which a subject is trained to respond differentially to two stimuli, and is subsequently trained under reversed reward values.

PERSEVERATION

The persistent use of a specific strategy to solve a problem, despite the fact that the strategy is wrong or the rule of the task has changed.

DIALECTICAL BEHAVIOUR THERAPY

A cognitive–behavioural approach that was originally developed to treat people with borderline personality disorder, especially those with chronic patterns of suicidal behaviour. As people with this disorder lack interpersonal skills and have an impaired self-image, the dialectical strategy aims to help the patients accept the way they are while simultaneously helping them to change.

HAPLOTYPE

A combination of alleles at different sites on a single chromosome.

MODIFIER GENE

A gene that influences the phenotypic expression of another gene.

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Mann, J. Neurobiology of suicidal behaviour. Nat Rev Neurosci 4, 819–828 (2003). https://doi.org/10.1038/nrn1220

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