The neural mechanisms of vulnerability to suicide in old age remain largely unknown, in part due to a paucity of empirical research. Although post-mortem and imaging studies have yielded a number of candidate neural markers, they are not connected to psychological and cognitive pathways to suicide. Our lab attempts to bridge this gap by investigating decision processes that lead to suicidal behavior. Suicide, especially in old age, is often viewed as a strategic, rational decision. In contrast, we argue that the suicidal criis often escalates unexpectedly, and catastrophic choices result from a failure to appropriately integrate moment-to- moment experiences with pre-existing knowledge and values. Empirically, such faulty integration is seen in people with a history of attempted suicide, who tend to make poor choices based on moment-to-moment feedback in reward/punishment-based learning experiments. The applicant's K23-supported preliminary study combining fMRI and computational modeling found that the suicidal persons'failure to integrate accumulating feedback is paralleled by disrupted paralimbic expected reward signals. The proposed study goes a step further by examining dynamic decision processes in suicidal people at multiple levels: reward signals measured through BOLD activation, corticostriatothalamic network integrity measured by functional connectivity, behavior during reward learning, dimensions of cognitive performance implicated in decision- making, and psychological traits relevant to real-world decisions.
Our first aim i s to investigate corticolimbic reward system alterations underlying biased decision-making in suicidal behavior. We focus on the neglect of vital information in decisions, test its association with attempted suicide and examine its neural underpinnings.
Our second aim explores the well-established link between poor executive control and suicidal behavior. We will test a putative pathway from disrupted neocortical top-down control over decision-making to failure of behavioral adaptation to suicidal ideation. We propose a cross-sectional case-control study with three groups of depressed participants (30 suicide attempters, 30 suicide ideators, 30 non-suicidal depressed elderly) and 30 non-psychiatric controls, recruited from an ongoing study of late-life suicidal behavior (PI: Szanto). Participants will complete a novel probabilistic reversal learning fMRI task, which experimentally manipulates multiple theoretically predicted signals (expected reward, reward probability, reward prediction error, volatility). Analyses of neural data will use a reinforcement learning model. The sampling strategy and detailed assessments are designed to minimize and control for confounding factors. The investigative team includes experts in functional (Siegle) and specifically geriatric (Aizeinstein) imaging, statistical analysis of neural data (Kass), decision neuroscience (Clark), and cognitive control (MacDonald). This work leverages powerful theoretical frameworks of formal learning theory and decision neuroscience. It will lay the groundwork for a dimensional classification of suicidal behavior and for discovery of intervention targets.

Public Health Relevance

Worldwide, suicide rates are higher in older adults than in any other age group;in this country, the burden of late-life suicide is likely to increase as the US population ages. Yet, we know very little about brain mechanisms that cause certain older people to be vulnerable to suicide. This important area remains under-researched.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH100095-01A1
Application #
8755148
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Niederehe, George T
Project Start
2014-08-01
Project End
2019-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$375,510
Indirect Cost
$125,510
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gujral, Swathi; Ogbagaber, Semhar; Dombrovski, Alexandre Y et al. (2016) Course of cognitive impairment following attempted suicide in older adults. Int J Geriatr Psychiatry 31:592-600
Kasckow, John; Youk, Ada; Anderson, Stewart J et al. (2016) Trajectories of suicidal ideation in depressed older adults undergoing antidepressant treatment. J Psychiatr Res 73:96-101
Vanyukov, P M; Szanto, K; Hallquist, M N et al. (2016) Paralimbic and lateral prefrontal encoding of reward value during intertemporal choice in attempted suicide. Psychol Med 46:381-91
Kay, Daniel B; Dombrovski, Alexandre Y; Buysse, Daniel J et al. (2016) Insomnia is associated with suicide attempt in middle-aged and older adults with depression. Int Psychogeriatr 28:613-9
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
de Bruin, Wändi Bruine; Dombrovski, Alexandre Y; Parker, Andrew M et al. (2016) Late-life Depression, Suicidal Ideation, and Attempted Suicide: The Role of Individual Differences in Maximizing, Regret, and Negative Decision Outcomes. J Behav Decis Mak 29:363-371
Vanyukov, Polina M; Szanto, Katalin; Hallquist, Michael et al. (2016) Perceived burdensomeness is associated with low-lethality suicide attempts, dysfunctional interpersonal style, and younger rather than older age. Int J Geriatr Psychiatry :
Dombrovski, A Y; Szanto, K; Clark, L et al. (2015) Corticostriatothalamic reward prediction error signals and executive control in late-life depression. Psychol Med 45:1413-24
Szanto, Katalin; Bruine de Bruin, Wändi; Parker, Andrew M et al. (2015) Decision-making competence and attempted suicide. J Clin Psychiatry 76:e1590-7
Chase, Henry W; Kumar, Poornima; Eickhoff, Simon B et al. (2015) Reinforcement learning models and their neural correlates: An activation likelihood estimation meta-analysis. Cogn Affect Behav Neurosci 15:435-59

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