A neural substrate of comorbid depressive symptoms in alcohol use
Alcohol use disorder (AUD) is commonly associated with depression, which may exacerbate the clinical outcome and increase treatment difficulty. The neural substrates underlying such comorbid symptoms are unclear. Here, we identify the regulatory role of amygdala Menin (multiple endocrine neoplasia type 1) signaling in orchestrating local GABAergic inhibition, which modulates the emotional state following alcohol use. Alcohol intake reduces Menin expression in the amygdala, decreasing GAT1 transcription. Restoring Menin signaling or overexpressing GAT1 in the amygdala could suppress alcohol preference and prevent depressive-like behaviors in these animals. Notably, knocking-in mice expressing a human MEN1 variant (Menin-G503D) that associates with MDD exhibit strong alcohol preference. These findings uncover a previously unknown mechanism for a common clinical element of alcohol addiction and point to a novel candidate therapeutic target against depression.
Authors
- Shangchen Yang
- Tingting Zou (ORCID: https://orcid.org/0000-0002-7240-1378)
- Ziqi Yuan (ORCID: https://orcid.org/0000-0003-3137-5246)
- Ti‐Fei Yuan (ORCID: https://orcid.org/0000-0003-0510-715X)
- Dan Can
- Lige Leng (ORCID: https://orcid.org/0000-0002-4288-4743)
- Kai Zhuang (ORCID: https://orcid.org/0000-0003-1724-6210)
- Zhenlei Chen (ORCID: https://orcid.org/0000-0003-1518-3463)
- Wang Ya (ORCID: https://orcid.org/0000-0002-5217-282X)
- Huifang Li (ORCID: https://orcid.org/0000-0003-2268-5496)
- Jie Zhang (ORCID: https://orcid.org/0000-0003-1040-5848)
- Jane Ding (ORCID: https://orcid.org/0000-0001-5909-5006)
Institutions
- Hebei Medical University (CN)
- Fujian Medical University (CN)
- Xiamen University (CN)
- Nantong University (CN)
- Shanghai Mental Health Center (CN)
- First Affiliated Hospital of Xiamen University (CN)
- Xiamen Maternal and Child Health Hospital (CN)
Publication Details
- Journal
- Molecular Psychiatry
- Published
- 2025-05-27
- DOI
- https://doi.org/10.1038/s41380-025-03061-6
- Citations
- 5
- Primary Topic
- Neurotransmitter Receptor Influence on Behavior
- Type
- article
- Field-Weighted Citation Impact
- 4.55
Funders
- National Natural Science Foundation of China
- Ministry of Education of the People's Republic of China
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities