# Neurobiological markers of risk and resilience for psychopathology in youth at familial risk for mood disorders

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $48,054

## Abstract

Among youth, major depressive disorder (MDD) and bipolar disorder (BD) represent two of the top ten causes
of disability and confer heightened risk of suicide. Since BD often initially presents as a MDD episode, youth with
BD are frequently misdiagnosed and thus receive ineffective treatment. Family history of mood disorders is a
robust predictor of early-onset MDD and BD as well as other psychiatric disorders. Prior studies have identified
neurobiological differences between healthy youth at high familial risk for BD or MDD relative to low familial risk,
and one study has identified neural circuit differences between youth at high familial risk for BD versus MDD.
Relatedly, there is preliminary evidence for neural markers that predict later onset of psychopathology among
youth at high familial risk for BD and MDD. These studies suggest that there are markers of vulnerability that
can be detected in the brain, prior to symptom onset, which may further increase risk for poor mental health
outcomes among these susceptible youth. However, extant research has been limited by small sample sizes
and a lack of multiple longitudinal symptom measurements over time, which have hindered the identification of
robust biomarkers that distinguish risk profiles among youth with a family history of BD versus MDD. The
identification of brain-based signatures of BD and MDD risk in youth would advance understanding of distinct
mechanisms underlying heightened vulnerability, which may ultimately inform approaches for earlier and more
accurate identification of these disorders. The present study aims to uncover unique neurobiological profiles of
high familial risk for BD and MDD among healthy youth, and to investigate whether these biomarkers predict the
subsequent onset and longitudinal course of psychopathology across adolescence. This study will include
healthy youth at low (LR, n=3,915) or high familial risk for MDD (HR-MDD, n=1,564) or BD (HR-BD, n=407) with
longitudinal data up to 3 years, derived from the landmark Adolescent Brain Cognitive Development (ABCD)
Study. Aim 1 will examine dissociable patterns of resting-state functional connectivity (FC) in emotion- and
reward-related networks at baseline between healthy HR-BD, HR-MDD, and LR youth, using a whole-brain seed-
to-voxel approach with the amygdala, ventral striatum, and dorsal striatum as seed regions of interest. Aim 2
will ascertain longitudinal trajectories of dimensional psychiatric symptoms across adolescence over 3 years in
high familial risk youth using group-based trajectory modeling. Aim 3 will investigate whether alterations in
baseline FC within emotion- and reward-related networks predicts the presence of a clinical diagnosis in later
adolescence and/or a more severe longitudinal course of dimensional symptoms across adolescence. This
research will reveal critical insight into the mechanisms that contribute to risk versus resilience in vulnerable
youth, potentially serving as key biological...

## Key facts

- **NIH application ID:** 10832967
- **Project number:** 5F31MH131246-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Bailey Holt-Gosselin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,054
- **Award type:** 5
- **Project period:** 2023-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832967

## Citation

> US National Institutes of Health, RePORTER application 10832967, Neurobiological markers of risk and resilience for psychopathology in youth at familial risk for mood disorders (5F31MH131246-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10832967. Licensed CC0.

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