The US is facing rising suicide rates. Yet, we have only a limited understanding of why some people, but not others, progress from contemplating to attempting suicide. In the past funding period, we have shown that depressed older adults whose decision-making is impaired are more likely to progress from suicidal ideation to action. Specifically, using decision experiments, computational modeling, and fMRI, we have found replicable deficits in learning and choice processes paralleled by altered ventromedial and dorsolateral prefrontal abstract learning signals. In this renewal application, we propose to extend these findings by examining how people at risk for suicide make decisions under cognitive and emotional demands that are more representative of the suicidal crisis. In our computational framework these demands include (i) a high information load and (ii) constraints on information processing imposed by time pressure and impending threats. We have developed and validated new experimental and computational methods for studying information-processing bottlenecks during decision-making. Specifically, our reinforcement learning computational model applied to behavioral and neuroimaging data, enables us to examine how people use their limited neurocomputational resources to make good decisions under high information load. Our preliminary studies show that decision-making in this context (i) relies on resource-rational strategies for managing information load, (ii) is subserved by dorsal attention and cingulo-opercular networks, (iii) is likely disrupted in attempted suicide, (iv) a deficit paralleled by abnormal dorsal attention network responses to information load. We thus propose to test the general hypothesis that people at risk for suicide are prone to information-processing bottlenecks arising from alterations in these cortical networks. We will perform decision experiments and cognitive computational models (Aim 1) in a discovery sample and a non-overlapping replication sample (n = 200 each) to ensure that findings are robust to the clinical and cognitive heterogeneity of suicidal behavior. Both samples will include individuals maximally representative of suicide victims, namely older depressed suicide attempters, about half of whom survived near-lethal attempts. Functional neuroimaging experiments manipulating information load will interrogate the neurocomputational dynamics of the dorsal attention network and cingulo-opercular network during decision- making in one sample (n = 200, Aim 2). A careful characterization of psychopathology, personality, cognition, psychotropic exposure and brain damage from suicide attempts will allow us to control for key confounds. The interdisciplinary team has expertise in mechanisms of suicidal behavior (Dombrovski), decision neuroscience (Dombrovski, McGuire, Hallquist), imaging methods (Hallquist), and suicide risk management (Szanto, Dombrovski). This work aligns with a key objective of the NIMH?s prioritized research agenda on suicide: ?to identify cognitive dysfunction/neural circuitry profiles ? associated with suicide risk? and taps into the reinforcement learning and limited capacity constructs of the RDoC framework.

Public Health Relevance

US suicide rates are rising, and clinicians need to better understand why some people and not others go on from thinking about suicide to acting on their thoughts. We will test the idea that people at risk for suicide fail to make good decisions in a crisis and will investigate why this may happen with decision experiments, brain imaging and mathematical models of decision-making.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH100095-07
Application #
10120727
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Evans, Jovier D
Project Start
2014-08-01
Project End
2025-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
7
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zhang, Ke; Szanto, Katalin; Clark, Luke et al. (2018) Behavioral empathy failures and suicidal behavior. Behav Res Ther :
Dombrovski, Alexandre Y; Aslinger, Elizabeth; Wright, Aidan G C et al. (2018) Losing the battle: Perceived status loss and contemplated or attempted suicide in older adults. Int J Geriatr Psychiatry 33:907-914
Hallquist, Michael N; Hall, Nathan T; Schreiber, Alison M et al. (2018) Interpersonal dysfunction in borderline personality: a decision neuroscience perspective. Curr Opin Psychol 21:94-104
Szanto, Katalin; Galfalvy, Hanga; Vanyukov, Polina M et al. (2018) Pathways to Late-Life Suicidal Behavior: Cluster Analysis and Predictive Validation of Suicidal Behavior in a Sample of Older Adults With Major Depression. J Clin Psychiatry 79:
Dombrovski, Alexandre Y; Hallquist, Michael N; Brown, Vanessa M et al. (2018) Value-Based Choice, Contingency Learning, and Suicidal Behavior in Mid- and Late-Life Depression. Biol Psychiatry :
Alessi, Maria; Szanto, Katalin; Dombrovski, Alexandre (2018) Motivations for attempting suicide in mid- and late-life. Int Psychogeriatr :1-13
Kenneally, Laura B; Sz?cs, Anna; Szántó, Katalin et al. (2018) Familial and social transmission of suicidal behavior in older adults. J Affect Disord 245:589-596
Dombrovski, Alexandre Y; Hallquist, Michael N (2017) The decision neuroscience perspective on suicidal behavior: evidence and hypotheses. Curr Opin Psychiatry 30:7-14
Vanyukov, Polina M; Szanto, Katalin; Hallquist, Michael et al. (2017) Perceived burdensomeness is associated with low-lethality suicide attempts, dysfunctional interpersonal style, and younger rather than older age. Int J Geriatr Psychiatry 32:788-797
Huang, Wen-Chien; Chan, Mei-Lin; Chen, Ming-Jen et al. (2016) Modulation of macrophage polarization and lung cancer cell stemness by MUC1 and development of a related small-molecule inhibitor pterostilbene. Oncotarget 7:39363-39375

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