Suicide survivors have a lower sensitivity to body signals due to low brain activity in the insular cortex


People who have survived a suicide attempt are less sensitive to bodily signals related to their heart and breath, and have a higher tolerance for pain, suggest new findings published today in eLife.

Accurately predicting the risk of suicide in an individual is one of the greatest challenges encountered by clinicians.

By identifying physical characteristics that differentiate people who have attempted suicide from those who have not, the study paves the way for future research aimed at identifying biological indicators of suicide risk.

Our brain constantly monitors the status of bodily signals that we need to stay alive, such as our heartbeat, our breath and pain caused by tissue damage to our skin.

‘Interoception’ describes the way the nervous system tracks the internal state of the body, helping us to perceive potential or actual threats and to act accordingly.

“Unlike most organisms, some humans are able to counteract these survival instincts through the act of suicide,” explains lead author Danielle DeVille, a PhD student at the Laureate Institute for Brain Research, Tulsa, Oklahoma, US.

“While experts have strived for decades to understand and prevent these deaths, we still don’t know enough about the factors that contribute to suicidal behaviour.”

To address this gap, DeVille and her colleagues conducted the first study that looks at whether blunted interoception is associated with a history of suicide attempts in people with psychiatric disorders, including depression, anxiety and post-traumatic stress disorder.

Their study involved 34 participants with a history of suicide attempts in the last five years as compared to a matched psychiatric reference sample of 68 participants with no history of suicide attempts.

The team examined interoceptive processing in the participants using a panel of tasks. These include a breath-hold challenge, a cold-pressor test – where an individual immerses a hand in icy water and has their heart rate and skin conductance measured – and heartbeat perception.

The researchers found that those who had attempted suicide tolerated the breath-hold and cold-pressor challenges for significantly longer than those who had not.

Additionally, this group was less able to accurately perceive their heartbeat than non-attempters.

“We found that this ‘interoceptive numbing’ was linked to lower brain activity in the insular cortex, a region that closely tracks the internal state of the body,” explains senior author Sahib Khalsa, Director of Clinical Operations at the Laureate Institute for Brain Research.

“This numbing was not influenced by the presence a psychiatric disorder, by a history of having considered suicide, or by having taken psychiatric medications, and this suggests it was most closely linked to the act of attempting suicide.”

Khalsa adds that these findings come with a number of limitations, including the fact that the study did not fully examine whether a history of considering suicide, versus making an actual attempt, has an independent impact on interoception.

“It is also difficult to judge from our study whether the observed differences in interoception represent innate characteristics of the individuals involved, or whether they reflect an emerging response as they progressed from suicidal thinking to suicidal action,” he says.

Despite these limitations, the authors say their work reveals a possible role of interoceptive dysfunction in distinguishing individuals at risk of suicide.

It also lays the groundwork for further studies to determine whether measuring interoception in individuals can improve the ability to predict their suicide risk.

The insular cortex is a key hub in emotional processing with connectivity to the PFC, particularly VPFC, as well as mesial temporal structures [93].

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Object name is 41380_2019_587_Fig2_HTML.jpg
Overview of brain regions included in this review. These brain regions have been most reported in neuroimaging studies investigating structural, functional, and molecular brain alterations associated with suicidal thoughts and behaviors, with a subset of regions grouped more broadly into ventral prefrontal cortex, dorsal prefrontal cortex, insula, mesial temporal, subcortical, and posterior regions. DMPFC dorsomedial prefrontal cortex, dACC dorsal anterior cingulate cortex, RMPFC rostromedial prefrontal cortex, mOFC medial orbitofrontal cortex, vACC ventral anterior cingulate cortex, PCC posterior cingulate cortex, Thal thalamus, VS ventral striatum, Hippo hippocampus, Amyg amygdala, DLPFC dorsolateral prefrontal cortex, RLPFC rostrolateral prefrontal cortex, IFG inferior frontal gyrus, lOFC lateral orbitofrontal cortex, Put putamen, Caud caudate

The insula plays an important role in interoceptive awareness for positive and negative internal states [94], including emotional and other types of pain, and understanding and sharing of other people’s emotional states [9596].

Only in more recent studies has insula structure and function and related behavior been investigated for its role in STBs. For example, on a behavioral level, interoceptive deficits have been reported among SAs compared with individuals who only thought about or planned suicide among general psychiatric outpatient adults [97] and predicted SI severity at 6-month follow-up in community adolescents [98].

Smaller insula volume has been reported in adult SAs with BPD [99], in a combined group with SZ/SZA/psychotic BD [36] and elderly with MDD [69].

Lower insula thickness was observed in adults in relation to SA in SZ [70] and SI in MDD [37]. Smaller insula volume was associated with higher attempt lethality and lower impulsivity in BPD [8799].

In contrast, larger insula volumes were reported in relation to attempt lethality in adults with BD [100]. It is possible that the type of insula differences relate to specific characteristics of the high lethality attempters, since larger insula volumes were also found in association with higher lifetime history of aggression in BPD [87].

Some findings in the PFC noted above in MDD extended to the insula, including associations between baseline 5-HT1a binding potential with SI and lethality of future attempts within a 2-year follow-up period [41] and of increased neuroinflammation (TPSO availability) [89].

SPECT research showed higher insula rCBF in adult SAs with MDD [101] at rest and higher insula fMRI activation was found in adults with MDD or BD with psychotic features during a cognitive control task with insula activity related to higher intensity of SI [51].

Higher insula fMRI activation was also associated with lower subjective value of gain and loss in adult SAs with MDD [91]. Lower activation in the posterior insula during social exclusion was found in adult SAs with MDD or BD, which was suggested to indicate a higher tolerance to pain via repeated exposure to painful and provocative experiences in subjects vulnerable to suicide [102].


Smaller insula volume has been associated with SAs and lower impulsivity in adults across various mental disorders, whilst, both smaller and larger insula volumes have been associated with higher attempt lethality.

fMRI studies found higher insular activation during reward processing and cognitive control in adult SAs with MDD, while lower insula activation was associated with a higher tolerance to social pain in adult SAs with MDD or BD.

Thus, there is preliminary evidence for an involvement of insular structural and functional alterations in SI and SAs. However, since very few studies have focussed on the insula and that both decreases and increases in insula alterations have been reported, more research is needed to elucidate the role of the insula in STBs.

Interestingly, immune challenges activate interoceptive brain pathways (including the insula), triggering alterations in mood and cognition, motivation, and neurovegetative processes [103].

Together with preliminary evidence of increased neuroinflammation in the insula related to SI, this suggests that the insula may be an important region for future studies of neuroinflammation and STBs.



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