Fight the Fire: Association of Cytokine Genomic Markers and Suicidal Behavior May Pave the Way for Future Therapies

Abstract

The fight against suicide is highly challenging as it may be one of the most complex and, at the same time, most threatening among all psychiatric phenomena. In spite of its huge impact, and despite advances in neurobiology research, understanding and predicting suicide remains a major challenge for both researchers and clinicians. To be able to identify those patients who are likely to engage in suicidal behaviors and identify suicide risk in a reliable and timely manner, we need more specific, novel biological and genetic markers/indicators to develop better screening and diagnostic methods, and in the next step to utilize these molecules as intervention targets. One such potential novel approach is offered by our increasing understanding of the involvement of neuroinflammation based on multiple observations of increased proinflammatory states underlying various psychiatric disorders, including suicidal behavior. The present paper overviews our existing understanding of the association between suicide and inflammation, including peripheral and central biomarkers, genetic and genomic markers, and our current knowledge of intervention in suicide risk using treatments influencing inflammation; also overviewing the next steps to be taken and obstacles to be overcome before we can utilize cytokines in the treatment of suicidal behavior.

The Patient’s Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression

“…The efficacy of anti-inflammatory treatments in reducing anhedonia seems to support the involvement of inflammation in the pathophysiology of such dimension [59,60]. Also, suicide pathogenesis has been associated with neuroinflammation [61] with a specific interrelationship that goes beyond the underlying psychiatric illness, such as major depression [62]. However, the brain-derived neurotrophic factor (BDNF) has been reported among the underlying mechanisms of the association between suicidality and depression [63].…”

Embers of the Past: Early Childhood Traumas Interact with Variation in P2RX7 Gene Implicated in Neuroinflammation on Markers of Current Suicide Risk

“…Nevertheless, the contribution of inflammatory processes to the pathophysiology of suicide is increasingly researched [2,4,9,24,26]. Inflammatory activation of the immune system in patients with a higher suicide risk has been investigated regarding cytokines in serum, cerebrospinal fluid, and postmortem studies [54][55][56].…”

“…Although suicidal thoughts and behaviours can be reduced by psychological treatments and pharmacotherapy (lithium, ketamine, esketamine, and clozapine) [6,7], there is no pharmacological intervention that has a sufficient established effectiveness in preventing suicide, creating an immense unmet need [2,8]. However, some studies suggest that drugs that have antisuicidal effects seem to exert anti-inflammatory action as well, and certain medications acting on the immune system may possess antisuicidal properties [4,9].…”

“…Disturbances in the immune system, especially inflammation, play a critical role in a range of psychiatric disorders, including schizophrenia, major depressive disorder, or bipolar disorder [20]. Several studies have suggested that inflammatory mediators are involved in the pathophysiology of suicide as well [9,[21][22][23][24][25][26]. Elevated markers of inflammation, such as C-reactive protein, proinflammatory cytokine IL-1β and IL-6, and TNF-α have been reported, both in suicidal patients' central nervous system and peripheral tissues, regardless of their primary diagnosis, age, and gender [4,27].…”