National Initiative to Prevent Suicide: A new proposal to improve the understanding and prevention of suicide

What will be the foreseeable outcome of this initiative?

The establishment of the NSD is expected to lead to better identification of those who are genetically at increased risk of suicide as well as biological factors (eg, inflammatory or other processes) and environmental factors (eg, drug abuse), which can turn that genetic risk into reality. Using research results made possible by the implementation of this proposal, objective testing can be developed to monitor risk more effectively than is currently possible using clinical assessment alone.

Furthermore, this work also can provide targets for developing new treatments. For example, there is convergence between the work of Niculescu et al,^5,6 who identified genetic biomarkers for mechanistic target of rapamycin (mTOR) signaling as a risk factor in individuals who died by suicide and the work of Li et al and other researchers,^16-18 whose findings have implicated mTOR-dependent synapse formation as a mechanism underlying the rapid (ie, within hours to a couple of days) antidepressant effects of N-methyl-d-aspartate antagonists, such as ketamine, CP-101,606, and esketamine. In fact, the authors of a study presented earlier this year reported that esketamine—an active enantiomer of ketamine—rapidly reduced suicidal ideation as well as other depressive symptoms in individuals admitted to the hospital for suicidal ideation.¹⁹ (mTOR is a serine/threonine protein kinase that regulates a number of biological processes in addition to synaptogenesis, including cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and autophagy.^20,21)

In aggregate, establishment of this proposed database will facilitate identification of biological (and therefore pharmaceutical) mechanisms beyond those involving biogenic amines, which have been the exclusive biological targets for antidepressants for the past 50 years.²² The likely consequences of the findings generated from research made possible by the proposed NSD will open completely new vistas for helping people at risk for suicide and psychiatric illnesses.

What foreseeable obstacles will need to be addressed?

Of course, obstacles and problems will arise but these will not exceed those encountered by the War on Cancer and they can similarly be overcome with sufficient public support and cooperation. Potential obstacles include:

• need for incremental funding
• obtaining the cooperation of the offices of each county medical examiner or coroner in a process that includes uniform systematic data collection
• determining the situations (eg, time after death and means of death) that will allow for meaningful collection of data such as RNA and inflammatory biomarkers
• establishing how data and particularly biological samples will be transported and stored
• issues related to privacy of health information particularly for relatives of suicide victims
• ensuring the reliability, validity, and comparability of the data received from different medical examiners and coroners.

With regard to the last issue, because stigma is associated with death by suicide, some true suicides could be missed, which would compromise sensitivity but simultaneously increase specificity. Other obstacles or problems may arise; however, I am certain that all such issues are surmountable and that the resulting NSD will be much better than what we have now and will propel our understanding of the biological underpinnings of the loss of life to suicide. (The author proposed a similar but even more ambitious plan 25 years ago,²³ but he believes that this is an idea whose time has come.)

Acknowledgments

The author thanks Wayne C. Drevets, MD, Alexander Niculescu, MD, PhD, John Oldman, MD, and John Savitz, PhD, David Sheehan, MD, and Matthew Macaluso, DO for their review and suggestions concerning this proposal/manuscript, and Kaylee Hervey, MPH, from the Sedgwick County Health Department, Wichita, Kansas, for her input. The author also thanks Ruth Ross, as always, for her excellent editing and general assistance.