Research Links Amygdala Neurons to Depression’s Negative Bias

A recent study by scientists at the Institut Pasteur and CNRS uncovers how neuron dysfunction in the amygdala contributes to the negative perception bias seen in depression, paving the way for new treatments.

In a groundbreaking study, scientists from the Institut Pasteur and the CNRS, in collaboration with psychiatrists from the Paris Psychiatry and Neurosciences GHU, Inserm and CEA, have uncovered a potential neural mechanism influencing the pervasive “negativity bias” of depression. Their research, published in Translational Psychiatry, suggests that depression alters neural circuits in the amygdala, a key brain region involved in processing emotions.

When in depression, one tends to perceive everyday situations in an excessively negative way. This negativity bias significantly hinders the quality of life for those affected, contributing to persistent depressive symptoms.

Depression impacts 15-20% of people at some point in their lives, with 30% showing resistance to conventional treatments. Understanding the neural underpinnings of depression is crucial for developing new therapies, especially for those who do not respond to current antidepressant medications.

“We now know that the amygdala is not only involved in our emotional response to environmental stimuli, fostering attraction or repulsion, but that it also plays a role in depression,” co-last author Mariana Alonso, the head of the Emotional Circuits group at the Institut Pasteur, said in a news release.

The research team discovered that depressive states reduce the activity of neurons responsible for pleasant perceptions and overactivate those encoding negative stimuli.

Using a mouse model exhibiting behaviors akin to human depression, such as anxiety and stress, the scientists noted a pronounced negative bias in response to olfactory stimuli.

“To analyze how the amygdala functions during depression, we measured the activity of some networks of neurons involved in the more or less negative interpretation of olfactory stimuli,” Alonso added.

The results showed that in depressive states, neurons that typically process positive stimuli are underactive, while those processing negative stimuli are hyperactive. This dysfunction in amygdala circuits drives the negative perception bias in depression.

The implications of these findings are significant.

“We were able to at least partly reverse the negative emotional bias induced in mice, and the related depressive behavior, by overactivating the neurons involved in the positive encoding of environmental stimuli,” added Alonso. “This is an interesting avenue to explore for the development of novel therapies.”

The team is now focusing its research on humans.

“We are now exploring in humans whether successfully treating a depressive episode depends on reactivating these neural networks,” Chantal Henry, a professor of psychiatry at Université de Paris and psychiatrist at the Centre hospitalier Sainte-Anne, said in the news release.

This research heralds a promising step toward understanding the neural basis of depression and potentially opens new therapeutic pathways for the millions struggling with this debilitating condition.