What if you could see suicidality? Visibility, may be the key to Suicide prevention.

“More people die by suicide than by homicide or war every year.”(1).

Suicide is a complex phenomenon. It’s an exclusively human response to extreme psychological pain (2). It’s impact is widespread impact, with around 700000 lives lost, but many more impacted. One of the greatest challenges in suicide prevention is that early signs are not always visible.

Blind spots make suicidality hard to predict. We’re mostly working backwards from what can be observed behaviourally (e.g. expressed suicidal thoughts or actions). Most assessment tools are limited and unsuitable for accurately predicting suicidal behaviour in meaningful measurable ways (3, cited in 1). Psychological, psychosocial, and cultural factors are important in suicide risk screening; however, they offer weak prediction and limited clinical use (4).

The problem of Invisibility:

Suicidal individuals don’t always reveal their intentions and just because someone presents with risk factors it doesn’t guarantee suicidality.  Not everyone exposed to the same factors reacts in the same way. Furthermore, because of stigmatisation, and fears of copycatting, deaths by suicide are often not talked about openly, which has only added to its “invisibility” in society.  Current treatment interventions have varied effectiveness. 

According to Suicide Prevention Australia one of the key gaps to prevention is greater understanding of suicide risk and training to support high risk groups and diverse cohorts. (5). There is an overwhelming consensus (95%) that organisations need more access to reliable suicide prevention data. (5)

The life saving potential of visibility: the case for neurobiology

There is no single theoretical model that explains suicidology, however biological models show promise in identifying patterns or precursors or biomarkers that indicate pathology and may be most observable, measurable and therefore predictive. The neurobiological phenotypes model (with clinical and cognitive perspectives) gives a useful framework for suicidality.  (8) Diagnosis of biological origins and markers of disease may be more generalisable. In the same way screening for cancer and diabetes can be lifesaving, if MRI screening was available for at risk groups it could offer lifesaving visibility.

Evidence suggests suicide is a disease of the brain, or at least is visible in the brain.  And it makes sense, to study the brain for answers to mental health questions. Abnormal neurophysiological, biochemical, endocrinological, neuroanatomical, cognitive, and neuropsychological presentations consistently accompany psychiatric illness. (6)

Neurobiology is the study of the nervous system, brain function and related structures. Up until recently neurobiology was understudied, but several biological markers, pathways and disruptions in brain regions show visible and measurable factors relating to suicide. Advances in technologies like neuroimaging and scanning have been pivotal in helping uncover nuances in neural networks and molecular and biochemical communication. (7)

Observable differences in the brain, visible in structural neuroimaging, were consistent with suicidal behaviours.  Studies showed grey matter volume was reduced overall in the brain, and other key structural patterns were observable in what researchers referred to as key “suicidal regions” (8, 9).  Some of these regions like the frontal and prefrontal cortex are regions particularly involved in stress response, suppression of impulsiveness and cognition. (7 cited (55)).

Research into biochemical pathways in the brain and brain regions that may affect suicidality is promising. (10). Post-mortem brain studies of people who died by suicide, also showed noticeable consistent biochemical changes. (10) Researchers in Australia are using available neurobiology research data to explore drug treatments further. (11) Early studies found Ketamine to be effective in preventing suicidality by up to 70% in the short term (7). 

Stress and suicide neurobiology links:

Part of the complexity of suicide prevention is modelling how biological processes are expressed as behaviour and thoughts.  The Stress diathesis model (how brain processes are involved in reactivity to stress) has linked suicidal thoughts and behaviour with dysregulation of the stress response system. (12)

Biological underpinnings play a key role in the way people react to stress.  There were visible neurobiological abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis and serotonergic neurotransmission (15) in people’s brains who died by suicide.  HPA axis hyperactivity is believed to substantially increase the odds of death by suicide (8).  

Gene and neurobiology links:

Gene studies also help us understand why there are different outcomes from exposure to an environmental pathogen.  (13)

Complex gene mapping (14) in the brains of people with and without mental disorders highlight many regulatory elements that coordinate the brains biological pathways and cellular functions.  This data helps to understand how brain structure and function contribute to mental disorders and other regulatory elements in the brain and the way genetic risk contributes to mental disorders.  This research can be expanded into suicide prevention by identifying predictive and protective factors. (14)

Suicidality is not connected to just one gene, its polygenic, and a strong epigenetic component is probable.   Genetic factors interact with biological and psychological -environmental factors that modify an individuals capacity to adapt, particularly due to neurobiological alterations.  (12)

Genome studies (GWAS) link 43% of suicidal behaviour to genetics.  (7) Over 2500 genes are associated with suicide (7).  Research on the genetic architecture of suicidal attempts identified biological and biochemical pathways of high clinical significance in suicidal samples, such as cortisol synthesis and secretion, glutamatergic synapse and circadian rhythm (with higher similarities for identical twins) (7). 

Certain therapies can alter how genes and biochemistry express themselves and affect health.  Scientists are tyring to pinpoint how these changes in the brain can be used to affect suicidal behaviour. 

Neurobiology may be used to accelerate suicide prevention by targeting two intervention approaches (16): selected interventions (to address needs of people who may be at higher risk of suicide) and indicated interventions (to address needs of people when they experience suicidality).  Most screening is low risk and non invasive.  Limitations at population level include access and expense. 

Conclusion:

Suicidal behaviour is a complicated multifactorial polygenic and independent mental disorder. Neurobiology may be foundational in targeted prevention initiatives, because of its potential for enhanced visibility. Biological risk factors may provide more visible, measurable and stronger predictors of suicidality. More focused research on the causal relationship between identifiable measurable biomarkers and the brain and suicidality may help us better predict and prevent suicide. Increased awareness, the generalisability of simple biomarkers, and shared suicide databases may provide better screening tools and greater reach. This increased visibility, may be the key to suicide predictability making it the best target for prevention. 

Reference list:

1.     Xenia Gonda, Peter Dome, Gianluca Serafini, Maurizio Pompili (2023). How to save a life: From neurobiological underpinnings to psychopharmacotherapies in the prevention of suicide, Pharmacology & Therapeutics (Vol 244)108390,ISSN 0163-7258, https://doi.org/10.1016/j.pharmthera.2023.108390.

2.     Schneidman

3.     ((Blasco-Fontecilla & de Leon, 2021; Chan et al., 2016; Fazel & Runeson, 2020; Saab et al., 2021 cited in Ghonda

4.     Dwivedi Y, editor. The Neurobiological Basis of Suicide. Boca Raton (FL): CRC Press/Taylor & Francis; 2012. Available from: https://www.ncbi.nlm.nih.gov/books/NBK107209/

5.     Suicide Prevention Australia National Policy. 2022. https://www.suicidepreventionaust.org/wp-content/uploads/2022/02/SPA_National-Policy-Platform_2022_FINAL.pdf

6.     (Gottesman & Gould, 2003). (Carballo)

7.     Abou Chahla MN, Khalil MI, Comai S, Brundin L, Erhardt S, Guillemin GJ. Biological Factors Underpinning Suicidal Behaviour: An Update. Brain Sci. 2023 Mar 16;13(3):505. doi: 10.3390/brainsci13030505. PMID: 36979315; PMCID: PMC10046421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046421/

8.     van Heeringen, K., & Mann, J. J. (2014). The neurobiology of suicide. Lancet Psychiatry, 1(1), 63-72.

9.     Domínguez-Baleón, C., L. F. Gutiérrez-Mondragón, A. I. Campos-González and M. E. Rentería (2018). Neuroimaging Studies of Suicidal Behavior and Non-suicidal Self-Injury in Psychiatric Patients: A Systematic Review. Frontiers in Psychiatry 9: 500. 

10.  Oldman and oquenda

11.  Can AT, Hermens DF, Dutton M, Gallay C, Jensen E, Jones M, Scherman J, Beaudequin DA, Yang C, Schwenn PE, Lagopoulos J (2021) Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study. Translational Psychiatry, 11: 101.

12.  Lengvenyte, A., I. Conejero, P. Courtet and E. Olié (2021). Biological bases of suicidal behaviours: A narrative review. European Journal of Neuroscience, 53(1): 330-351. 

13.  Caspi & Moffat. (2006) Gene environment interactiosn in Psychiatry

14.  National Institutes of Health (NIH). PsychENCODE: Decoding Mental Health With Advanced Brain Gene Maps (June, 2024), TOPICS:BrainGeneticsNational Institutes of HealthNeurosciencePopular https://scitechdaily.com/decoding-mental-health-with-advanced-brain-gene-maps/

15.  O'Connor, D. B., Green, J. A., Ferguson, E., O'Carroll, R. E., & O'Connor, R. C. (2017). Cortisol reactivity and suicidal behavior: Investigating the role of hypothalamic-pituitary-adrenal axis responses to stress in suicide attempters and ideators. Psychoneuroendocrinology, 75, 183-191. 

16.  USI model by the Institute of Medicine (1994)

17.  WHO 2019

18.  McHugh, C. M., Iorfino, F., Crouse, J. J., Tickell, A., Nichles, A., Zmicerevska, N., . . . Hickie, I. B. (2021). Neurocognitive functioning predicts suicidal behaviour in young people with affective disorders. Journal of Affective Disorders, 281, 289-296.