17
Series
Suicide 1
The neurobiology of suicide
Kees van Heeringen, J John Mann
The stress–diathesis model posits that suicide is the result of an interaction between state-dependent (environmental)
stressors and a trait-like diathesis or susceptibility to suicidal behaviour, independent of psychiatric disorders.
Findings from post-mortem studies of the brain and from genomic and in-vivo neuroimaging studies indicate a
biological basis for this diathesis, indicating the importance of neurobiological screening and interventions, in
addition to cognitive and mood interventions, in the prevention of suicide. Early-life adversity and epigenetic
mechanisms might explain some of the link between suicide risk and brain circuitry and neurochemistry
abnormalities. Results from a range of studies using diverse designs and post-mortem and in-vivo techniques show
impairments of the serotonin neurotransmitter system and the hypothalamic–pituitary–adrenal axis stress-response
system in the diathesis for suicidal behaviour. These impairments manifest as impaired cognitive control of mood,
pessimism, reactive aggressive traits, impaired problem solving, over-reactivity to negative social signs, excessive
emotional pain, and suicidal ideation, leading to suicidal behaviour. Biomarkers related to the diathesis might help to
inform risk-assessment procedures and treatment choice in the prevention of suicide.
Neurobiology of suicide: introduction
Prediction of risk of suicide and identification of
treatment and prevention targets beyond major
psychiatric illnesses are objectives to improve suicide
prevention. Available clinical predictors are scarce and no
biomarkers have been established to help clinicians to
predict suicidal behaviour or to target with treatment. A
proposed stress–diathesis model of suicidal behaviour
describes it to be the result of an interaction between
stressors and a susceptibility to suicidal behaviour
(diathesis). The biological correlates of the trait–diathesis
could provide biomarkers for suicide risk that are
distinguishable from biomarkers of co-occurring
psychiatric disorders and that might help to predict risk
after exposure to stressors such as an acute psychiatric
disorder or adverse psychosocial events.
1,2
Although
suicidal behaviour is heterogeneous and varies in degree
of intent and amount of clinical damage done, suicide
deaths and non-fatal but highly lethal suicide attempts
are similar from demographical, clinical, and
neurobiological perspectives, and therefore probably
have a common diathesis (figure 1).
3
Most people with major psychiatric disorders never
manifest suicidal behaviour, indicating the importance
of diathesis in addition to a disorder. About 50% of the
risk of suicide due to diathesis is inherited, and this
percentage is possibly higher in women than in men.
4,5
Epigenetic effects of childhood adversity (eg, life-events
such as physical or sexual abuse) might also increase an
individual’s risk of suicidal behaviour through an effect
on their diathesis and an increase in their risk of mood
disorders.
6
Genetic and epigenetic pathways to suicidal
behaviour might therefore link genes and the clinical
and cognitive manifestations of biological-intermediate
phenotypes.
7
The stress–diathesis model provides an
opportunity to integrate neurobiological phenotypes with
clinical and cognitive perspectives in the study and
prevention of suicide. Therefore, in this Series paper we
describe the neurobiological basis of suicide, and focus
on clinical and cognitive manifestations that might be
related to impairments in mood regulation and decision
making, involving serotonergic, hypothalamic
pituitary
adrenal axis, noradrenergic, and other neurobiological
abnormalities.
From cells to circuits
Cells
Post-mortem studies of people who have died by suicide
show changes in several cell types (neurons and glial
cells such as astrocytes and oligodendrocytes) in cortical
and subcortical areas of the brain.
In the brainstem,
suicide seems associated with more serotonin neurons
and more tryptophan hydroxylase 2 (TPH2; the rate-
limiting enzyme in the synthesis of serotonin) gene
expression and protein per neuron, and possibly higher
serotonin concentrations, compared with individuals
who have died suddenly from causes other than suicide
and who did not have a psychiatric illness.
8
People with
untreated depression who have died by suicide had fewer
mature granule neurons in the hippocampus (specifically
in the dentate gyrus) than had people with depression
given selective serotonin-reuptake inhibitors before their
Published
Online
May 2, 2014
S2215-0366(14)70220-2
This is the first in a
Series
of
three papers about suicide
Unit for Suicide Research,
Department of Psychiatry and
Medical Psychology, Faculty of
Medicine and Health Sciences,
Ghent University, Ghent ,
Belgium
(Prof K van Heeringen PhD)
; and
Molecular Imaging and
Neuropathology Division,
Department of Psychiatry,
Columbia University, NY, USA
(Prof J J Mann MD)
Correspondence to:
Prof Kees van Heeringen, Unit for
Suicide Research, Department of
Psychiatry and Medical
Psychology, Faculty of Medicine
and Health Sciences, Ghent
University, University Hospital,
Ghent 9000, Belgium
cornelis.vanheeringen@ugent.
be
Figure 1:
The stress–diathesis model of suicidal behaviour
Genetics; childhood traumatic
events
Diathesis
Sensitivity to social stress;
impulsivity; pessimism or
hopelessness
Psychiatric disorders;
psychosocial adverse events
Stress
Financial or marital problems;
exacerbation of psychiatric
disorder; emotional pain
Suicidal behaviour
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