Research story · 01
The resilience question
Two mice go through the same repeated social stress. One keeps engaging with others. The other starts to avoid them. We look for what's different inside their brains.
Photo: UA College of Medicine – Phoenix Media Productions, 2019
The question
Why does chronic stress lead to depression in some individuals but not others?
Chronic stress is one of the strongest risk factors for depression, yet people exposed to the same stress respond very differently. Some develop depression. Others adapt. And more than half of patients do not reach full remission with current treatments.
Our lab asks what makes the difference: which circuits, cells and synapses in the brain's reward system tip the balance toward susceptibility or resilience.
The story · 2:15
Why the same stress leads to depression in some mice but not others: the cells, genes and circuit our lab has found.
Chapters
- Featured studies
- Kim et al., Mol Psychiatry 2021 · Kim et al., Biol Psychiatry 2024 · Ma et al., Transl Psychiatry 2026
- Collaboration
- Qiu Lab (Shenfeng Qiu, MD, PhD), UA College of Medicine – Phoenix
- Brain model
- Allen Mouse Brain Common Coordinate Framework v3, Allen Institute for Brain Science
- Funding
- National Institute of Mental Health, R01MH128192
Big questions
What we want to know
- 01Which cells in the brain's reward hub change when stress wins?
- 02How does Shisa6 reshape the connections of D1 neurons during chronic stress?
- 03How does SIRT1 tune the genes that control how D1 neurons fire?
- 04How do signals from the prefrontal cortex differ in resilient brains?
- 05Can these targets lead to faster-acting antidepressants?
Including work from Dr. Ferguson's postdoctoral training
Key papers
Transl Psychiatry · 2026
A nucleus accumbens-projecting prefrontal cortex circuit underlies chronic social stress-induced depression-like behaviors
Ma X, Kim H, Zhang L, Chen P, Wei J, Cui Y, …, Ferguson D, Qiu S
Biol Psychiatry · 2024
SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens
Kim HD, Wei J, Call T, Ma X, Quintus NT, Summers AJ, …, Qiu S, Ferguson D
Mol Psychiatry · 2021
Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens
Kim HD, Wei J, Call T, Quintus NT, Summers AJ, Carotenuto S, …, Qiu S, Ferguson D
J Neurosci · 2016
SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens
Kim HD, Hesterman J, Call T, Magazu S, Keeley E, Armenta K, …, Nestler EJ, Ferguson D
Nature · 2014
β-catenin mediates stress resilience through Dicer1/microRNA regulation
Dias C, Feng J, Sun H, Shao NY, Mazei-Robison MS, Damez-Werno D, …, Shen L, Nestler EJ
Nature · 2013
Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons
Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, …, Nestler EJ, Han MH
Funding
- NIH / NIMH R01MH128192, Prefrontal–Accumbens Neurocircuits Mediating Response to Social Stress (2022–2027)
Collaborators
- Qiu Lab, UA College of Medicine – Phoenix
