Skip to main content
Journal cover image

Neural mechanism underlying depressive-like state associated with social status loss.

Publication ,  Journal Article
Fan, Z; Chang, J; Liang, Y; Zhu, H; Zhang, C; Zheng, D; Wang, J; Xu, Y; Li, Q-J; Hu, H
Published in: Cell
February 2, 2023

Downward social mobility is a well-known mental risk factor for depression, but its neural mechanism remains elusive. Here, by forcing mice to lose against their subordinates in a non-violent social contest, we lower their social ranks stably and induce depressive-like behaviors. These rank-decline-associated depressive-like behaviors can be reversed by regaining social status. In vivo fiber photometry and single-unit electrophysiological recording show that forced loss, but not natural loss, generates negative reward prediction error (RPE). Through the lateral hypothalamus, the RPE strongly activates the brain's anti-reward center, the lateral habenula (LHb). LHb activation inhibits the medial prefrontal cortex (mPFC) that controls social competitiveness and reinforces retreats in contests. These results reveal the core neural mechanisms mutually promoting social status loss and depressive behaviors. The intertwined neuronal signaling controlling mPFC and LHb activities provides a mechanistic foundation for the crosstalk between social mobility and psychological disorder, unveiling a promising target for intervention.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 2, 2023

Volume

186

Issue

3

Start / End Page

560 / 576.e17

Location

United States

Related Subject Headings

  • Social Status
  • Social Behavior
  • Reward
  • Mice
  • Habenula
  • Developmental Biology
  • Depression
  • Animals
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fan, Z., Chang, J., Liang, Y., Zhu, H., Zhang, C., Zheng, D., … Hu, H. (2023). Neural mechanism underlying depressive-like state associated with social status loss. Cell, 186(3), 560-576.e17. https://doi.org/10.1016/j.cell.2022.12.033
Fan, Zhengxiao, Jiarui Chang, Yilan Liang, Hong Zhu, Chaoyi Zhang, Diyang Zheng, Junying Wang, Ying Xu, Qi-Jing Li, and Hailan Hu. “Neural mechanism underlying depressive-like state associated with social status loss.Cell 186, no. 3 (February 2, 2023): 560-576.e17. https://doi.org/10.1016/j.cell.2022.12.033.
Fan Z, Chang J, Liang Y, Zhu H, Zhang C, Zheng D, et al. Neural mechanism underlying depressive-like state associated with social status loss. Cell. 2023 Feb 2;186(3):560-576.e17.
Fan, Zhengxiao, et al. “Neural mechanism underlying depressive-like state associated with social status loss.Cell, vol. 186, no. 3, Feb. 2023, pp. 560-576.e17. Pubmed, doi:10.1016/j.cell.2022.12.033.
Fan Z, Chang J, Liang Y, Zhu H, Zhang C, Zheng D, Wang J, Xu Y, Li Q-J, Hu H. Neural mechanism underlying depressive-like state associated with social status loss. Cell. 2023 Feb 2;186(3):560-576.e17.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

February 2, 2023

Volume

186

Issue

3

Start / End Page

560 / 576.e17

Location

United States

Related Subject Headings

  • Social Status
  • Social Behavior
  • Reward
  • Mice
  • Habenula
  • Developmental Biology
  • Depression
  • Animals
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences