18
Series
death by suicide or had people without a psychiatric
disorder who died a sudden death that was not due to
suicide. In parallel, in people with depression who died
by suicide, the volume of the dentate gyrus is smaller,
and there is less angiogenesis, in people not treated than
in those who were treated before death.
9
In the
noradrenergic system, there seems to be a deficiency of
noradrenergic neurons in the locus coeruleus of people
who have died by suicide compared with individuals
without psychiatric disorders who have died a sudden
death.
10
In mood disorders, three patterns of
morphometric cellular changes are noted—cell loss
including loss of glia (in the subgenual prefrontal cortex),
cell atrophy or lower neuronal density (dorsolateral
prefrontal cortex and orbitofrontal cortex), and increased
numbers of serotonin cells (dorsal raphe nucleus).
11
Circuits
Neuroimaging studies link brain circuitry and localised
changes in neurochemistry to mood regulation, reactive
aggression, and decision making components of the
diathesis. Functional MRI allows imaging of activity in
certain brain regions, and use of molecular neuroimaging
techniques can quantify specific neurotransmitter
systems in people who have attempted suicide but not
died and compare them with those in control individuals
with psychiatric disorders
to investigate directly the
diathesis for suicidal behaviour.
Most molecular imaging studies have focused on the
serotonin system. Two brain regions, one in the anterior
cingulate and medial prefrontal cortex, and one in the
lateral prefrontal cortex, were shown to have activity that
was correlated with lethality (degree of medical injury
sustained as assessed with the Beck Medical Damage
Scale) of suicidal behaviour in people with major
depression. This relation, as measured by relative
F‑fluorodeoxyglucose (FDG) uptake
on PET, was
mediated by degree of suicidal intent (positive correlation
between degree of intent and medical injury due to the
attempt) and severity of impulsive trait (negative
correlation between impulsivity and medical injury). The
regional difference in brain activity between people who
had made high-lethality suicide attempts and those who
had made low-lethality suicide attempts was more
pronounced in individuals given fenfluramine, a drug
that causes a robust release of serotonin. Prefrontal
localised hypofunction and impaired serotonergic
responsivity in people who have attempted suicide was
proportional to the lethality of suicide attempts.
12
Later
imaging studies showed that the uptake of
C‑methyltryptophan (an analogue of the essential
aminoacid tryptophan needed for synthesis of serotonin)
is low in the orbital medial prefrontal cortex of people who
have attempted suicide and in proportion to the degree of
suicide intent.
13
PET studies show a deficit of serotonin
transporter binding in the serotonin neurons of people
with depression who have attempted suicide compared
with those of people with depression who did not attempt
suicide or those of healthy individuals.
14,15
This finding is
similar to that of the deficit in serotonin-transporter
expression and binding reported in post-mortem studies
of people who have died by suicide. Conversely,
investigators have noted higher brainstem 5-HT
1A
binding
in people with depression who have attempted suicide,
which was greatest in people who had higher intent and
did more medical damage. These findings are consistent
with lower transporter binding and higher 5-HT
1A
binding
in the prefrontal cortex and brainstem people who have
died by suicide.
16
Two studies showed no difference in
dopamine-transporter binding between people who
attempted suicide and control individuals with depression,
but more studies of other neurotransmitter systems are
needed in relation to suicidal behaviour.
17,18
A further molecular imaging study investigated brain
activity associated with the emotional pain of major
depression that might lead to suicide.
19,20
Greater
emotional pain in individuals with depression was
associated both with risk of suicide and with changes in
activity in several brain areas, including the dorsolateral
prefrontal cortex and the inferior frontal gyrus.
20
Thus,
despite the limited anatomical distribution of tracer
targets and insufficient sensitivity to quantify the
receptors in all of the brain regions where they are
present, molecular imaging studies have begun to
identify the neural circuitry of suicidal behaviour, and
particularly, to implicate an abnormal serotonin system
in more lethal suicidal behaviour.
Imaging studies have explored further with use of MRI
the neural circuitry of individuals who show non-fatal
suicidal behaviour (tables 1 and 2).
21
Structural findings
(table 1) include mainly right-sided deficits in volumes of
grey matter in cortical areas (orbitofrontal, dorsolateral
prefrontal, insula, and superior temporal gyrus) and
basal ganglia (caudate and globus pallidus). The volumes
of thalamus and right amygdala seem to be greater in
suicide attempters. Findings of white-matter hyper­
intensities (particularly periventricularly), increased
bilateral volumes of inferior frontal white-matter tracts
(particularly
in the uncinate fasciculus and inferior
orbitofrontal fasciculus), and lower anisotropy in the left
orbitofrontal area and the left anterior limb of the internal
capsule, indicate that there are structural connectivity
impairments linked to suicidal behaviour.
Functional neuroimaging findings (table 2) associated
with suicidal behaviour include changed reactivity to
several stimuli, noted mainly in bilateral orbitofrontal,
right ventromedial and anterior cingulate, and left
dorsolateral prefrontal cortex areas. Functional
connectivity is decreased between anterior cingulate and
posterior insula, and connectivity increased in a striatal
motor–sensory network.
Although the identified structural and functional
correlates of suicidal behaviour could serve many
alternative functions, they are components of brain
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