Stressed Out? Your Brain Might Be at Risk for Depression

Researchers have found that a group of neurons in the hypothalamus, called proopiomelanocortin (POMC) neurons, become overactive after prolonged stress. This overactivity can lead to problematic behaviors such as depression and a decreased ability to feel pleasure, also known as anhedonia. 

The study published in Molecular Psychiatry showed that when the activity of POMC neurons was decreased, these problematic behaviors were mitigated. 

The researchers studied the effects of chronic, unpredictable stress on POMC neurons in male and female mice. They found that the stressors increased the firing of these neurons, which led to anhedonia and behavioral despair. When the researchers suppressed the neuronal activity, stress-related behavioral alterations in males and females were reduced. 

The study suggests that increased firing of POMC neurons is a driver of subsequent behavioral alterations like depression, and that this increase is "both necessary and sufficient" to increase vulnerability to stress. The hypothalamic arcuate nucleus (ARC), a bow-shaped brain area, is home to the POMC neurons and is known to have a role in how chronic stress impacts behavior. 

AgRP neurons, which also reside in the ARC, have a role in how chronic stress impacts behavior. AgRP activation decreases alongside behavioral alterations like anhedonia, and stimulating those neurons reduces the behaviors. The yin-yang interaction between AgRP neurons and POMC neurons is well-documented, and chronic stress can disturb the balance between these two neuronal populations. 

Potassium channels in POMC neurons may play a role in dampening the neurons’ excitation by allowing potassium to flow out of the cell. Activating these potassium channels could be a viable targeted treatment to limit the wildly firing POMC neurons, but more research is needed.