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NPAS4 genetic biomarker for depression symptoms identified in an animal study

Scientists at the Medical University of South Carolina (MUSC) have identified a stress-regulated gene that is responsible for the link between long-term stress and anhedonia, or the loss of interest in previously pleasurable activities, in an animal study using mice.

Research has shown that a transcription factor called NPAS4 in the medial prefrontal cortex (mPFC) is regulated by chronic social defeat stress (CSDS) and is required in this brain region for CSDS-induced changes in sucrose preference and natural reward motivation in mice. This gene did not affect other depressive symptoms, such as social avoidance and anxiety.

The findings suggest that there is not one central mechanism by which stress causes the varied symptoms of depression, and effective treatments might need to target distinct brain mechanisms. The study’s findings may help inform how to target more effectively the parts of the brain that are most relevant to the symptoms someone is experiencing.


  1. Hughes BW, Siemsen BM, Tsvetkov E, et al. NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses. eLife. 2023;12. doi:

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