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Identification of Positive Valence System Related Targets for Novel Suicide Prevention Approaches


Sarah Hollingsworth Lisanby, M.D.
Division of Translational Research


The primary objective of this Funding Opportunity Announcement (FOA) is to advance translational research to better understand risk and resilience for suicide in the context of the Research Domain Criteria (RDoC) framework and the Positive Valence Systems (PVS) domain. The PVS domain includes three major constructs: Reward Responsiveness, Reward Learning, and Reward Valuation and associated sub-constructs. This objective may be achieved by 1) investigating the role of PVS deficits in individuals with suicidal thoughts and behaviors; 2) using differences in constructs within the PVS domain and related neural circuitry to identify unique subtypes; 3) exploring how these PVS domain-related subtypes are associated with factors in other domains (e.g., social processes, negative valence, cognitive processes); and, 4) identifying and evaluating relevant modifiable behavioral and neural intervention targets. Outcomes of this FOA may lead to a better understanding of risk and resilience for suicide and identification of novel behavioral or neurobiological intervention targets for the treatment of suicidality using the RDoC framework. In particular, identification and validation of intervention targets would be based on understanding the nature of PVS deficits in individuals exhibiting suicidal ideation or behavior considered along a continuum or in comparison with individuals not exhibiting suicidal ideation or behavior. Treatment development would be beyond the scope of this FOA, but proof-of-concept studies will be encouraged.


There is an urgent public health need to effectively intervene to mitigate increasing suicide rates across the lifespan. Prospective RDoC studies in suicide to date focus primarily on predictors in the Negative Valence Systems domain such as hopelessness and rumination, highlighting a clear gap relating to reward and other PVS systems. Research examining PVS in suicidal individuals has the potential to improve our understanding of the transition through the ideation to action framework, as difficulty engaging in normally reinforcing activities and experiencing and learning from pleasure may be indicative of or lead to elevated risk. The objectives of the FOA closely reflect the goals of the Prioritized Research Agenda for Suicide Prevention  in addressing the following questions:

  • Why do people become suicidal? Studies under this FOA could identify biomarkers and dysfunctions which are associated with suicide risk;
  • How can we better or more optimally detect/prevent risk? Studies could assess when changes in PVS occur in relation to suicidal behavior; and,
  • What interventions are effective? What prevents individuals from engaging in suicidal behavior?

Studies supported under this FOA could identify targets to guide the choice of intervention or provide a rationale for developing new interventions specifically focused on identified PVS deficits. This focus has the potential to broaden understanding of suicidal behavior in the context of a full range of affective experiences and processes. This knowledge may foster the discovery of more precise or new intervention targets in individuals exhibiting suicidal ideation or behavior, which may improve therapeutic outcomes in suicide prevention.