# Positive and Negative Valence Systems Underlying Suicide in Youth

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $461,438

## Abstract

PROJECT SUMMARY/ABSTRACT
Suicide is a major public health concern in adolescents and the second leading cause of death in this age group,
highlighting the need to investigate suicide in adolescents. The two most prominent risk factors for completed
suicide in youth are a past suicide attempt and a diagnosis of a depressive episode, each independently
representing a 10- to 30-fold increased risk for completed suicide. However, while over 80% of suicidal youth
present with depressive symptoms at the time of the attempt, only 30% of depressed youth will ever attempt
suicide. These data suggest that depressed adolescents with prior suicide attempts represent a distinct
neurobiological subgroup. However, at present, we have no biomarkers to identify those depressed youth who
will engage in suicidal behavior. This proposal addresses this concern. Our proposed model is: (1) anhedonia is
associated with heightened suicidal risk in depressed youth; (2) both positive valence (PVS) deficits (reward
expectancy, attainment, positive prediction error) and negative valence (NVS) hyperactivity (negative prediction
error, pain avoidance) contribute to anhedonia and underlie suicidal behavior in depressed youth; (3) the
habenula (Hb), a small limbic hub, plays a key role in PVS/NVS processes by inhibiting reward signaling in
response to pain and loss; and (4) recent advances in high-resolution MRI address prior technical constraints in
studying small structures such as the Hb. These advances now allow us to study the neuronal circuitry underlying
PVS and NVS in a neuroanatomically rigorous framework. In support, we documented that of adolescent
depression’s core symptoms, only anhedonia, not irritability, was associated with suicidality among depressed
youth. Similarly, we found that both anhedonia and entrapment were independently associated with suicidality
in acutely suicidal hospitalized individuals. We also developed the reward flanker (RFT) and reward prediction
error (RPET) fMRI tasks and identified brain function during reward anticipation, attainment, and positive and
negative prediction errors. Notably, both RPET and a thermal pain task elicited measurable Hb activation.
Additionally, utilizing an optimized segmentation and seeding approach, we mapped Hb intrinsic functional
connectivity in adults and in adolescents with psychiatric symptoms. Building upon our work, we propose a tightly
integrative study to test the overall hypothesis that both PVS deficiency and NVS hyperactivity underlie suicidal
behavior in depressed youth. We will study 30 suicidal and 30 non-suicidal depressed adolescents, ages 12-17,
group matched for age, sex, and handedness. All will have comprehensive clinical evaluations (diagnoses,
behavioral measures, computerized reward task). Neuroimaging studies will include structural MRI, resting-state
and task fMRI (RFT, RPET, thermal pain). Machine learning algorithms will be used to examine which PVS/NVS
processes predict suicidal beh...

## Key facts

- **NIH application ID:** 9892475
- **Project number:** 1R21MH121920-01
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Vilma Gabbay
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $461,438
- **Award type:** 1
- **Project period:** 2020-04-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892475

## Citation

> US National Institutes of Health, RePORTER application 9892475, Positive and Negative Valence Systems Underlying Suicide in Youth (1R21MH121920-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9892475. Licensed CC0.

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