Have you ever felt an absence of joy— a feeling so pervasive that can’t be erased, not by your favorite snack, your beloved hobbies, or anything that you once enjoyed. That feeling, when it lingers, could be more than sadness—it might be depression. Affecting over 21 million people (1), depression is a serious mental health condition that goes far beyond feeling down for a few days. It can interfere with motivation, pleasure, and even basic daily tasks. Scientists are uncovering how depression changes the way our brain sees rewards, and it could transform how we treat this serious condition.

How the Brain Processes Rewards—and How Depression Gets in the Way

Imagine something that you enjoy such as a favorite pastime or a tasty snack. Your brain uses information in the environment and past experiences to recognize those things as rewards, prompting you to seek them out again. Unfortunately, this system is disrupted for many people with depression. Rewards become hard to identify and even basic pleasures lose their spark.

Why does this happen? Scientists are working to understand how depression affects the brain’s reward system and find ways to fix these issues. A new study from researchers at the University of California-San Francisco and Columbia University offers promising insights.

Using Mice to Understand Changes in the Brain’s Reward System

To conduct their studies, scientists turned to a valuable candidate: mice. Mouse brains process rewards in ways similar to humans and they pursue rewards like humans, making them a useful model for studying the brain’s reward system. 

The scientists performed a sucrose preference test. When given a choice between plain water and a sweet, sugary drink, most mice (like many of us) choose the sugar aka sucrose preference. But following a stressful situation, while some mice lost their sucrose preference (“susceptible” group), other mice didn’t (“resilient” group). This loss of sucrose preference in mice is seen as a stand-in for the human experience of anhedonia, or the inability to experience joy or pleasure that often accompanies depression.

What’s Going on in the Brain?

We have learned that the brain performs a series of calculations to identify rewards. This study measured the brain activity in two regions: the ventral hippocampus, which helps in stress and emotion regulation (2), and the basolateral amygdala, involved in reward learning (3). When functioning properly these brain regions help mice and humans recognize rewards. While the healthy, “resilient” mice’s brains were functioning as expected, the stress “susceptible” mice couldn’t properly discriminate between high and low-value rewards and as a result, they no longer sought out the high-value rewards.

Can the Brain’s Joy Circuitry Be Repaired?

Here’s where it gets exciting: the scientists didn’t stop at observing the difference. They also tried to fix it. Specifically, they wanted to test whether adjusting activity in certain brain regions would restore the mice’s sucrose preference. They stimulated brain activity between the ventral hippocampus and basolateral amygdala.

The result? The scientists found that increasing activity in these regions reversed the changes they previously observed. Now the “susceptible” mice’s brains could properly discriminate the reward values. Astonishingly, this change in brain activity was accompanied by a change in behavior, with the “susceptible” mice again preferring the sweet drink. In other words, restoring the brain’s reward system.

These exciting results suggest that dysfunction in the ventral hippocampus and basolateral amygdala disrupted the brain’s ability to identify rewards. Without proper reward calculation, mice were not able to correctly select the sugary drink. If we can restore the reward calculation in mice, can the same be done in humans?

What This Means for Treating Depression

Modifying brain activity in humans is not a foreign concept. A process called deep brain stimulation, which involves delivering electrical impulses to specific brain regions, has been used as a treatment for depression. However, the current brain areas targeted may not provide relief for all people. This new study suggests that the ventral hippocampus and basolateral amygdala may be possible targets for deep brain stimulation in the future. 

While the inability to experience joy or pleasure is a feature of depression, it also appears in other disorders such as alcohol use disorder (4) and post-traumatic stress disorder (5). That means this line of research could expand the treatment options available for not only depression, but for other mental health conditions as well. The idea is simple but powerful: if we can help the brain rediscover what brings joy, we can help people feel like themselves again.

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Additional References:

1. Substance Abuse and Mental Health Services Administration. (2022). Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/report/2021-nsduh-annual-national-report
2. Fanselow MS, Dong HW. (2010). Are the dorsal and ventral hippocampus functionally distinct structures? Neuron, 65(1):7-19. https://doi.org/10.1016/j.neuron.2009.11.031
3. Sun Y, Gooch H, Sah P. (2020) Fear conditioning and the basolateral amygdala. F1000Research, 9, 53. https://doi.org/10.12688/f1000research.21201.1
4. Hatzigiakoumis, D. S., Martinotti, G., Giannantonio, M. D., & Janiri, L. (2011). Anhedonia and substance dependence: Clinical correlates and treatment options. Frontiers in Psychiatry, 2(10). https://doi.org/10.3389/fpsyt.2011.00010
5. Vinograd, M., Stout, D. M., & Risbrough, V. B. (2022). Anhedonia in Posttraumatic Stress Disorder: Prevalence, phenotypes, and neural circuitry. Current Topics in Behavioral Neurosciences, 185–199. https://doi.org/10.1007/7854_2021_292