Alexandre Y. Dombrovski MD

A. Personal Statement

I direct the Decision Neuroscience and Psychopathology Laboratory at the University of Pittsburgh. I have a career-long interest in learning processes that underlie psychopathology and, in current longstanding collaborations, have studied learning and decision-making, with suicide being a key area of interest. I have coauthored over 30 peer-reviewed papers, 17 of them in the past 5 years.

I will also be responsible for participant recruitment and retention, inclusion/exclusion decisions, clinical and cognitive characterization, and suicide risk management across both sites, as well as all data collection procedures at the Pitt site. I will oversee the preprocessing of all physiological data and personally conduct multi-level analysis of EEG and ECG on Pitt’s high-performance cluster, using pipelines we have developed in the past five years.
My lab investigates the decision-making and learning deficits that underlie suicide and other forms of psychopathology, as well as their neurocomputational substrates. I use behavioral experiments, recordings of neural data, and reinforcement learning models. For more than 18 years, I have conducted research with high-suicide-risk populations. As a practicing psychiatrist, I see patients with difficult-to-treat mood disorders, cognitive disorders, personality disorders, and suicidal behavior, and my clinical observations inform the theoretical perspective articulated in this proposal.

1. Tsypes A, Hallquist MN, Ianni A, Kaurin A, Wright AGC, Dombrovski, AY. Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression. JAMA Psychiatry. 2024 Oct 1;81(10):1010–1019. PMCID: PMC11238070
2. Allen, TA, Hallquist, MN, & Dombrovski, AY. (2024). Callousness, exploitativeness, and tracking of cooperation incentives in the human default network. PNAS, 121(29), e2307221121. PMID: 38980906. PMCID: PMC11260090.
3. Hallquist, MN, Hwang, K, Luna, B, Dombrovski, AY. (2024) Reinforcement-based option competition in the dorsal stream during exploration/exploitation of a continuous space. Science Advances, 10 (8). PMID: 38394198. PMCID: PMC10889364
4. Dombrovski, AY.*, Luna B, Hallquist MN*. Differential reinforcement encoding along the hippocampal long axis helps resolve the explore-exploit dilemma. Nat Commun. 2020 26;11(1):5407. PMID: 33106508. PMCID: PMC7589536.

Ongoing projects that I would like to highlight include:

R01MH124092
Neurocomputational studies of mood-related momentum dynamics linking reward learning, valuation and responsivity
Dombrovski, Alexandre Y. (MPI), Hallquist, Michael N. (MPI), Eldar, Eran (MPI)
Role: Contact PI
10/01/2020 – 9/30/2025
This study tests a computational model of coupling between mood and reinforcement and examines its implications for mood instability.

Neurocomputational Studies of Mood-related Momentum Dynamics Linking Reward Learning, Valuation and Responsivity

R01 MH048463
Psychobiology of Suicidal Behavior in Borderline Personality Disorder
Dombrovski, Alexandre Y. (PI)
04/01/2023 – 03/31/2028
Role: PI
This study examines the emergence of suicidal thoughts and behavior in borderline personality at timescales of years (gradual decompensation), days (affective dysregulation), and minutes (moment-to-moment decision-making) using long-term follow-up, ambulatory assessments, passive sensing, behavioral experiments, reinforcement learning modeling and fMRI.

Psychobiology of Suicidal Behavior in Borderline Personality Disorder

R01 MH100095
Reward Learning in Late-Life Suicidal Behavior
Dombrovski, Alexandre Y. (PI)
03/01/20-02/28/25
Role: PI
This study examines the alterations in the way older depressed people prone to suicide make moment-to-moment decisions in an uncertain, changing environment, using functional imaging augmented with reinforcement learning computational models.

Reward Learning in Late-Life Suicidal Behavior

B. Positions, Scientific Appointments, and Honors

Positions
2024 -               Professor of Psychiatry, University of Pittsburgh, Pittsburgh, PA
2015 - 2024     Associate Professor of Psychiatry, University of Pittsburgh, Pittsburgh, PA
2007 - 2015     Assistant Professor of Psychiatry, University of Pittsburgh, Pittsburgh, PA

Scientific Appointments
2011 -     Member, International Academy of Suicide Research (IASR)
2009 -     Member, Society for Biological Psychiatry (SOBP)
2005 -     Member, American Association of Geriatric Psychiatry (AAGP)

Honors
2018     American Society for Clinical Investigation
2013     Young Investigator Research Award, American Foundation of Suicide Prevention
2010     Travel Fellowship, American College of Neuropsychopharmacology
2008     Travel Award, Society for Biological Psychiatry (SOBP)
2007     Member-in-Training Research Award, American Association of Geriatric Psychiatry (AAGP)
2006     Eleventh Annual APA Research Colloquium for Junior Investigators, American Psychiatric Association
2006     Outstanding Adult Teaching Award, Western Psychiatric Institute and Clinic
2006     New Investigator Award, New Clinical Drug Evaluation Unit (NCDEU)
2005     Lilly Chief Resident Executive Leadership Program, American Psychiatric Association (APA)
2005     Fellowship in Geriatric Psychiatry, American Association of Geriatric Psychiatry (AAGP)
1997     Mayor's Stipend, Merit-based Award from the Mayor of Moscow

C. Contributions to Science
a. Decisions under uncertainty involve a difficult tradeoff between exploiting familiar valuable options and exploring unfamiliar and potentially superior ones (e/e dilemma). I am interested in how humans resolve the e/e dilemma when facing a multitude of options. We proposed a reinforcement learning model which relies on information compression to facilitate the transition from exploration to exploitation. Using this model, we have investigated neural mechanisms underlying the explore/exploit balance in the human hippocampus and dorsal stream.

1. Hallquist, MN, Hwang, K, Luna, B, Dombrovski, AY. (2024) Reinforcement-based option competition in the dorsal stream during exploration/exploitation of a continuous space. Science Advances, 10 (8). PMID: 38394198. PMCID: PMC10889364
2. Dombrovski, AY.*, Luna B, Hallquist MN*. Differential reinforcement encoding along the hippocampal long axis helps resolve the explore-exploit dilemma. Nat Commun. 2020 26;11(1):5407. PMID: 33106508. PMCID: PMC7589536
3. Hallquist MN*, Dombrovski AY*. Selective Maintenance of Value Information Helps Resolve the Exploration/Exploitation Dilemma. Cognition 2019 Feb;183:226-243. PMID: 30502584. PMCID: PMC6328060.
4. Brown, V.M., Hallquist, M.N., Frank, M.J., and Dombrovski, AY. (2022). Humans adaptively resolve the explore-exploit dilemma under cognitive constraints: Evidence from a multi-armed bandit task. Cognition 229, 105233. PMID: 35917612. PMCID: PMC9530017.

b. Suicide is often viewed as a strategic, rational decision. We argue that, in reality, the suicidal crisis escalates unexpectedly. Catastrophic choices stem from a failure to appraise recent events and options in the context of prior experience and values. To understand the mechanisms of this failure, we studied suicidal individuals’ decision-making in experiments involving risk, uncertainty, and time. We have identified replicable deficits in learning under uncertainty as well as choice processes, paralleled by disrupted expected value (reward) signals in the ventromedial prefrontal cortex.

1. Tsypes A, Hallquist MN, Ianni A, Kaurin A, Wright AGC, Dombrovski AY. Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression. JAMA Psychiatry. 2024 Oct 1;81(10):1010–1019. PMCID: PMC11238070
2. Tsypes A, Szanto K, Bridge JA, Brown VM, Keilp JG, Dombrovski AY. Delay discounting in suicidal behavior: Myopic preference or inconsistent valuation? J Psychopathol Clin Sci. 2022 Jan;131(1):34–44. PMID: 34843269. PMCID: PMC8893041.
3. Dombrovski AY, Hallquist MN, Brown VM, Wilson J, Szanto K. Value-Based Choice, Contingency Learning, and Suicidal Behavior in Mid- and Late-Life Depression. Biological Psychiatry. 2019 Mar;85(6):506–516. PMID: 30502081. PMCID: PMC6380943.
4. Dombrovski AY, Szanto K, Clark L, Reynolds CF, Siegle GJ. Reward signals, attempted suicide, and impulsivity in late-life depression. JAMA Psychiatry. 2013 Oct;70(10):1. PMID: 23925710. PMCID: PMC3859132.

c. Interpersonal conflict is one of the more common precipitants of suicidal crises, in people with critical vulnerabilities. These vulnerabilities have traditionally been thought of as forms of psychopathology or personality traits. Using dimensional models of psychopathology, we have shown that antagonism prospectively predicts the occurrence of major interpersonal stressors across the life course, consistent with a stress generation process. In ecological momentary assessment studies, we have shown that interpersonal perceptions of others’ warmth can catalyze suicidal ideation, especially in those prone to hostile negative affect. This finding replicates at longer timescales, where interpersonal conflict elicits suicidal ideation, and eventually suicidal behavior, particularly for individuals are high in trait disinhibition.

1. Allen TA, Dombrovski AY, Soloff PH, Hallquist MN. Borderline personality disorder: stress reactivity or stress generation? A prospective dimensional study. Psychol Med. 2022 Apr;52(6):1014-1021. doi: 10.1017/S003329172000255X. Epub 2020 Jul 27. PMID: 32713398; PMCID: PMC8988096.
2. Allen TA, Hallquist MN, Wright AGC, Dombrovski AY. Negative Affectivity and Disinhibition as Moderators of an Interpersonal Pathway to Suicidal Behavior in Borderline Personality Disorder. Clinical Psychological Science. SAGE Publications Inc; 2022 Sep;10(5):856-868. PMID: 36172259. PMCID: PMC9514132.
3. Kaurin A, Dombrovski AY, Hallquist MN, Wright AGC. Suicidal urges and attempted suicide at multiple time scales in borderline personality disorder. J Affect Disord. 2023 May 15;329:581-588. doi: 10.1016/j.jad.2023.02.034. Epub 2023 Feb 11. PMID: 36781143; PMCID: PMC10693674.
4. Kaurin A, Dombrovski AY, Hallquist MN, Wright AGC. Momentary interpersonal processes of suicidal surges in borderline personality disorder. Psychol Med. 2022 Oct;52(13):2702-2712. doi: 10.1017/S0033291720004791. Epub 2020 Dec 10. PMID: 33298227; PMCID: PMC8190164.

d. Understanding what makes people vulnerable to conflict is critical for improving psychiatric diagnosis and treatment and, particularly, for suicide prevention. To explore this question, we developed game theory-based experiments and computational cognitive models to examine how people learn and adjust their behavior based on others’ actions. This work has revealed cortico-striatal social learning signals indicating that people encode predicted others’ cooperations and defections as rewarding, reinforcing their social policy. Critically, these learning signals are positively related to exploitativeness and negatively related to
callousness. Finally, interview and self-report data suggest that loss of social status may be an important component of exploitativeness. We have examined behavioral responses to status threats experimentally, observing differential impact of narcissistic traits and depression.

1. Allen TA, Hallquist MN, Dombrovski AY. Callousness, exploitativeness, and tracking of cooperation incentives in the human default network. Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2307221121. doi: 10.1073/pnas.2307221121. Epub 2024 Jul 9. PMID: 38980906; PMCID: PMC11260090.
2. Vanyukov PM, Hallquist MN, Delgado M, Szanto K, Dombrovski AY. Neurocomputational mechanisms of adaptive learning in social exchanges. Cogn Affect Behav Neurosci. 2019 Aug;19(4):985-997. doi: 10.3758/s13415-019-00697-0. PMID: 30756349; PMCID: PMC6690806.
3. Edershile EA, Szücs A, Dombrovski AY, Wright AGC. Dynamics of narcissistic grandiosity and vulnerability in naturalistic and experimental settings. J Pers Soc Psychol. 2024 Jul;127(1):199–216. PMCID: PMC11326982
4. Szücs A, Edershile EA, Wright AGC, Dombrovski AY. Rivalry and admiration-seeking in a social competition: From traits to behaviors through contextual cues. Personal Disord. 2023 Jul;14(4):429-440. doi: 10.1037/per0000610. Epub 2023 Jan 2. PMID: 36595438; PMCID: PMC10313745.

e. Antidepressant placebos have a profound effect on mood, which often dwarfs the drugs’ pharmacodynamic effects. Building on insights from placebo analgesia research, we have conducted a series of acute and
subacute experimental studies, which begin to uncover the interplay between expectancies, learning processes and mood underlying the antidepressant placebo effect.

1. Peciña M, Chen J, Karp JF, Dombrovski AY. Dynamic Feedback Between Antidepressant Placebo Expectancies and Mood. JAMA Psychiatry. 2023 Apr 1;80(4):389–398. PMCID: PMC9979016
2. Peciña M, Chen J, Lyew T, Karp JF, Dombrovski AY. μ Opioid Antagonist Naltrexone Partially Abolishes the Antidepressant Placebo Effect and Reduces Orbitofrontal Cortex Encoding of Reinforcement. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Oct;6(10):1002–1012. PMCID: PMC8419202
3. Handoko K, Neppach A, Snyder I, Karim HT, Dombrovski, AY. Peciña M. “Expectancy-Mood Neural Dynamics Predict Mechanisms of Short- and Long-Term Antidepressant Placebo Effects". Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, accepted for publication. Early online publication: 2025 Jan 11; PMID and PMCID pending
4. Chen J, Mizuno A, Lyew T, Karim HT, Karp JF, Dombrovski AY, Peciña M. Naltrexone modulates contextual processing in depression. Neuropsychopharmacology. Nature Publishing Group; 2020 Nov;45(12):2070–2078. PMID: 32843703; PMCID: PMC7547720

Full bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/alexandre.dombrovski.1/bibliography/public/