20
Series
overvalue signs of social rejection, as indicated by hyper-
reactivity to angry faces.
43,47
This susceptibility resembles
sensitivity to signals of defeat, which has been formulated
in cognitive models of suicide.
54
The involved brain
circuitry determines the processes that individuals use to
control cognitively which emotions they generate and
then to decide how to deal with these emotions.
Susceptible individuals might experience intense mental
pain that they find difficult to control. Deficiencies in
decision-making processes might restrict the extent of
choices so that suicide might be considered the only way
to stop the intense, unrelenting, emotional pain.
53
From causes to pathophysiology
Causes
Stressors such as life events and psychiatric disorders are
important risk factors for suicide, but the diathesis
concept explains why only few individuals exposed to
these stressors will take their own life. Early-life adversity
and epigenetic mechanisms seem to be related to causal
mechanisms for this diathesis.
55
Findings from cross-
sectional and longitudinal studies have shown that early-
life adversity is one of the strongest risk factors for
suicide, even after adjustment for other major risk factors
such as psychopathology.
56
The experience of repeated
acts of abuse, particularly physical and sexual abuse,
increases risk of suicidal behaviour throughout life.
Epigenetic mechanisms could explain the association
between childhood experiences and reactivity to stressors
in later life, mediated in part by the hypothalamic–
pituitary–adreno–cortical axis.
57
About 50% of the risk for suicide or suicide attempts is
heritable. The specific genes are not confirmed. One
genome-wide study of individuals who had attempted
suicide did not show a significant link between attempts
and any single nucleotide polymorphism.
58
Another
study identified a region within
ABI3BP
, but this finding
was not replicated in a second cohort.
59
Data from a meta-
analysis (8700 individuals with mood disorders)
identified four candidate regions, one of which included
the protein kinase C-ε (
PRKCE
) gene.
59
Investigators of a
later study did not report any single nucleotide
polymorphisms that reached the traditional p<5× 10
threshold for significance, but when they used gene
expression data from people who died by suicide to
screen their findings, they identified a cluster of genes
involved in neuroimmune functions.
60
A genome-wide
association study of individuals with bipolar disorder
reported an association signal on 2p25 at a threshold of
genome-wide significance.
61
Antidepressant-treatment-emergent suicidal ideation
might reflect a susceptibility to suicidal ideation in
individuals, but no reports of genome-wide association
studies have noted any variant associated with it that
reached genome-wide significance.
62
Investigators using
a genome-wide expression profile have identified genes
associated with glutamate and GABA cortical neuro­
trans­mitters, growth factors, polyamines, synaptic
Study population
Measurement
Main findings for people who attempted suicide compared
with controls
Disorder
People
who had
attempted
suicide (n)
Psychiatric
controls
(n)
Individuals
without
mental illness
(n)
Jollant et al,
43
2008
Major depression 13
14
16
Response to
emotional faces
Greater reactivity to angry faces in right orbitofrontal cortex; decreased
reactivity in right dorsolateral prefrontal cortex
Jollant et al,
44
2010
Major depression 13
12
0
Iowa GamblingTask Decreased activation during risky choices in left lateral orbitofrontal
cortex and occipital cortices
Pan et al,
45
2011
Major depression
(adolescents)
15
15
14
Go or no-go task
Differential activation of right anterior cingulate cortex during
response inhibition
Marchand et al,
46
2012 Major depression
6
16
0
Putamen functional
connectivity
Association with striatal motor–sensory network
Pan et al,
47
2013
Major depression
(adolescents)
15
14
13
Iowa GamblingTask No difference during learning in the context of risk
Pan et al,
48
2013
Major depression
(adolescents)
14
15
15
Response to
emotional faces
Greater reactivity to angry faces in right dorsal anterior cingulate cortex
and left dorsolateral prefrontal cortex, decreased functional
connectivity between right anterior cingulate cortex and bilateral
posterior insulae
Dombrovski et al,
49
2013 Major depression
(aged >65 years)
15
18
20
Reward prediction Weakened expected reward signal in ventromedial prefrontal cortex
(pregenual anterior cingulate cortex)
Fan et al,
50
2013
Major depression
27
10
57
Amplitude of low-
frequency fluctuation
Amplitude of low-frequency fluctuation increased in right superior
temporal gyrus and decreased in right ventromedial prefrontal cortex
Marchand et al,
51
2013 Major depression
7
13
21
Motor-activation
paradigm
Association with functional connectivity in striatal motor circuit
Table 2:
Functional MRI studies done in people who have attempted suicide
For the
Series
paper by
O’Connor and Nock see
/
S2215-0366(14)70222-6
1...,14,15,16,17,18,19,20,21,22,23 25,26,27,28,29,30,31,32,33,34,...56