Suicide is a devastating public health problem, claiming hundreds of thousands of lives worldwide each year.
Understanding the underlying biological and psychological factors that increase suicide risk is key for developing effective prevention and intervention approaches.
A recent article comprehensively reviews research on biological markers of suicidal thoughts and behaviors, providing important insights and guidance for future suicide research and prevention efforts.
Key Takeaways:
- No definitive biomarkers for suicide risk have been identified, but some show promise, including inflammatory cytokines, cortisol, brain-derived neurotrophic factor (BDNF), serotonin, lipids, C-reactive protein, leptin, and folate.
- Combinations of biomarkers may be more predictive than individual markers alone due to the complex, multifaceted nature of suicide risk.
- Longitudinal studies evaluating biomarker changes over time and in relation to emergence of suicidal thoughts or behaviors are greatly needed.
- Biomarker differences based on specific characteristics like psychiatric diagnosis, suicide attempt characteristics, and brain region underscore the heterogeneity of suicide risk.
- Both central and peripheral biomarkers are relevant for understanding suicide, but more central nervous system studies are needed.
Source: Korean College of Neuropsychopharmacology 2022
The Complex, Multifaceted Nature of Suicide Risk
Suicidal behavior encompasses a range of thoughts and behaviors along a continuum, from suicidal ideation to suicide attempts and death by suicide.
The development of suicide risk is complex, involving an interplay of biological, psychological, social and environmental factors.
This helps explain why identifying definitive biomarkers for suicide has remained elusive.
Rather than being attributed to single genes or biomarkers, suicide risk may be better conceptualized through a “stress-diathesis model”.
In this model, suicide may be triggered in vulnerable individuals by stressful life events interacting with underlying biological and psychological predispositions.
Consistent with this, the reviewed studies found associations between suicidal thoughts and behaviors and various disruption in biological systems related to stress, emotion regulation, cognitive functioning and impulsivity.
Many studies measured biomarkers in the blood, which is easily accessible.
However, some also measured biomarkers in cerebrospinal fluid or post-mortem brain samples to gain insights into central nervous system changes associated with suicide.
The review highlights the relevance of both peripheral and central biomarkers for understanding the complex underpinnings of suicide risk.
Key Biological Systems and Biomarkers Implicated in Suicide Risk
Inflammation
- Increased inflammatory cytokines like interleukin-1, interleukin-6 and tumor necrosis factor-alpha in the central nervous system have been associated with suicidal ideation and future suicide death.
- Mixed findings for associations between peripheral inflammatory markers and suicide risk.
- C-reactive protein levels may be increased in those with recent suicide attempts.
HPA Axis Regulation
- Findings are mixed regarding associations between cortisol levels and suicide risk. Some studies have found associations, others have not.
- Dysregulation of the HPA axis stress response system likely contributes to suicide risk in interaction with other vulnerabilities.
Brain Plasticity
- Lower peripheral blood BDNF levels may be associated with suicidal behavior, but findings are mixed.
- Reduced BDNF is consistently found in the post-mortem brains of those dying by suicide.
Serotonin
- Lower peripheral serotonin levels are associated with suicidal ideation. Findings are mixed for attempts and death.
- Post-mortem studies show differences in serotonin levels in specific brain regions of those dying by suicide.
Lipids
- Lower cholesterol levels may be associated with suicidal behavior and death by suicide.
Leptin
- A potential marker that may be reduced in those with suicidal ideation and attempts, but more research is needed.
Folate
- Lower folate levels may help predict future suicidal ideation and attempts.
The Need for Longitudinal Studies
Most studies to date have been cross-sectional comparisons between individuals with and without suicidal thoughts or behaviors.
Such studies provide limited insights about biomarker changes over time.
The review authors highlight the great need for more longitudinal studies to understand how biomarkers may dynamically change with emergence or fluctuation in suicide risk.
Studies with longer-term follow-up are also vital for evaluating whether biomarkers can predict future suicidal behaviors, not just correlate with current risk.
Preliminary evidence suggests some biomarkers like inflammatory cytokines, folate, and BDNF may have predictive ability, but more longitudinal research is needed.
Accounting for Heterogeneity in Suicide Risk
Not all individuals who die by suicide have a prior mental health diagnosis or treatment.
Additionally, risk profiles likely differ between those with and without known mental illness.
Biomarker profiles associated with suicide also appear to vary based on brain region, specific aspects of suicidal thoughts and behaviors, and other individual factors.
For example, studies have uncovered differences in inflammatory markers, BDNF, and serotonin levels across different brain regions between suicide decedents and controls.
Biomarker profiles also appear to differ in association with suicidal ideation versus attempts versus suicide death.
Specific psychiatric diagnoses like depression and schizophrenia may also show differential biological underpinnings related to suicide.
Furthermore, factors like the lethality of attempts, presence of violent tendencies, and having multiple attempts may relate to variations in suicide risk biomarkers.
The heterogeneity evident in the literature highlights the need for suicide research and prevention to utilize more personalized, precise approaches accounting for each individual’s unique risk profile.
Combining Biomarkers to Improve Suicide Prediction
The multifaceted nature of suicide indicates biomarkers are unlikely to explain or predict risk on their own.
Combining panels of relevant biomarkers may allow for better assessment of suicide risk.
Some preliminary studies have successfully utilized multi-marker approaches, but more research is warranted.
In addition to biological markers, incorporating psychological, social and environmental risk factors will be key for achieving an integrated understanding of suicide risk.
Advanced strategies like machine learning and AI could help identify complex patterns across diverse risk factors that may be difficult to discern using traditional statistical techniques.
Future Directions in Biomarkers for Suicidal Ideation
In summary, this comprehensive review synthesizes current knowledge on biological underpinnings of suicide risk and emphasizes important future directions for research.
A key conclusion is that longitudinal studies are critically needed to clarify how biological systems dynamically change over time with fluctuations in suicide risk.
Large collaborative efforts that allow integrating data across different studies, diagnosis groups and nations can help achieve sample sizes needed for evaluating biomarker predictive ability.
Research programs focused specifically on understanding suicide biology across multiple levels using standardized approaches and methodologies will also be highly informative.
While no definitive biomarkers for suicide have yet emerged, pursuing further research in this area remains a worthy investment for reducing the tragic loss of life to suicide.
Biomarker identification could augment current approaches to suicide risk screening, monitoring high-risk groups like those with mental illnesses, and developing new prevention and treatment innovations.
Even absent specific biomarkers, learning about suicide biology has intrinsic value for better understanding this perplexing phenomenon.
Integrating biological findings with psychological and social factors will provide a more holistic perspective.
This knowledge can help reduce stigma around suicide and underscore it as a complex condition involving multiple interacting predisposing and precipitating factors.
Overall, elucidating the biological basis of suicide risk remains an important research priority with major implications for advancing suicide prediction, prevention and treatment.
While challenges persist, maintaining a long-term focus on this goal will ultimately help illuminate the path to saving lives.
References
- Study: Peripheral biomarkers of suicidal behavior: current findings and clinical implications
- Authors: Hee-Ju Kang et al. (2022)
