In a new study, researchers found that a tiny population of neurons known to be important to appetite may also have a big role in depression that results from unpredictable, chronic stress.
The researchers found that chronic, unpredictable stress which erupts in the personal and professional lives, can change the function of AgRP neurons and may contribute to depression.
The small number of AgRP neurons likely are logical treatment targets for depression.
The research was conducted by Medical College of Georgia scientists.
Major depression is one of the most common mental health disorders in the United States, according to the National Institute of Mental Health, with an estimated 17.3 million adults experiencing at least one episode.
Prevalence rates are highest among 18-25-year-olds, females having about twice the risk of men, and depression can run in families.
Only about one-third of patients achieve full remission with existing treatments and anhedonia, the inability to experience pleasure, which increases suicide risk, typically is the last symptom to resolve.
However, the mechanisms behind depression’s effects remain poorly understood.
In the study, the team found that unpredictable chronic stress over time could lead to depression and decreases the activity of AgRP. This results in behavioral reactions.
Additionally, when they used a small molecule to directly inhibit the neurons, it increased their susceptibility to chronic, unpredictable stress, inducing depression-like behavior in the mice.
When they activated the neurons, it reversed classic depressive behaviors like despair and the inability to experience a pleasure.
The findings show that AgRP neurons are a key component to the neural circuitry underlying depression-like behavior, they write, and chronic stress causes AgRP dysfunction.
The team hopes the study can help find better ways to treat depression, including more targeted treatments that may reduce side effects, which often are strong enough to prompt patients to stop taking them.
Undesirable effects can include weight gain and insomnia.
One author of the study is Dr. Xin-Yun Lu, the chair of the Department of Neuroscience and Regenerative Medicine.
The study is published in Molecular Psychiatry.
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