In patients with major depression and high inflammation (CRP above 2 mg/L), the dopamine precursor L-DOPA did something placebo did not. It made the brain’s reward circuit work together better. That change went along with less loss of pleasure. It points to L-DOPA as a treatment for depression driven by inflammation.
Depression affects millions of people worldwide. The World Health Organization calls it a leading cause of disability around the world. And it has become much more common in the last few decades. Many things drive this, including genes, surroundings, and lifestyle. Also, the shame around mental illness can keep people from seeking help and getting proper care. Neurotransmitters are brain chemicals that carry signals between nerve cells. They play a key role in how the brain works. Several of them are involved in depression, including serotonin, norepinephrine, and dopamine. Serotonin is often called the “feel-good” chemical. It helps control mood, appetite, and sleep. Norepinephrine drives the body’s “fight or flight” response. It controls attention, alertness, and arousal. Dopamine helps control drive, reward, and pleasure. How they work in depression is complex. We do not fully understand it. But research suggests that imbalances in them may help cause depression. For example, low serotonin is linked to depression symptoms. Drugs that raise serotonin in the brain are often used to treat depression. In recent years, more and more evidence points to a role for brain inflammation in depression. Inflammation is the body’s normal response to injury or germs. But when it lasts, it can help cause many diseases. Depression is one. Studies show that people with depression have more inflammation markers in their blood and spinal fluid. One theory: inflammation in the brain throws these chemicals off balance. Inflammation can also affect the HPA axis (hypothalamic-pituitary-adrenal axis), which controls the body’s stress response. Problems with the HPA axis have been linked to depression. Also, long-term stress can lead to an overactive immune system and chronic inflammation. This in turn can lower neurotrophic factors. These are proteins that help nerve cells grow and survive. Lower levels weaken the brain circuits that control mood.
Can a dopamine drug help depression caused by inflammation?
One thing that feeds depression is inflammation. It is the body’s normal response to injury or germs. But when it lasts a long time, it can help cause depression. Past studies show that brain inflammation can affect how dopamine is made and released. Dopamine helps control mood, reward, and pleasure. Researchers wanted to test this link in the brain. So they studied patients with major depressive disorder (MDD). The patients were grouped by a blood marker of inflammation, C-reactive protein (CRP). Each got a single dose of the dopamine precursor levodopa (L-DOPA) and a placebo in a double-blind, randomized order about one week apart. The main outcome was resting-state functional connectivity (rsFC). It shows how well parts of a reward circuit in the brain talk to each other at rest. Patients with CRP levels higher than 2 mg/L who got L-DOPA showed a positive rsFC response compared with placebo. So L-DOPA may help the reward circuit work better. That may ease low mood in these patients. The study also looked at anhedonia, a symptom of depression where a person cannot feel pleasure. Stronger rsFC after L-DOPA went with lower anhedonia scores, but only in patients with CRP levels higher than 2 mg/L. So L-DOPA may help bring back pleasure in these patients. In short, this study suggests that inflammation can affect the brain’s dopamine system. That can help cause depression. So L-DOPA may be a way to treat depression in people with high inflammation.
Frequently asked questions
Can inflammation cause depression?
Long-term inflammation can help cause depression. People with depression have more inflammation markers in their blood and spinal fluid. Brain inflammation seems to upset the balance of brain chemicals. It also seems to disturb the HPA axis that runs the body’s stress response. And it seems to lower the neurotrophic factors that help nerve cells grow and survive. Each of those changes can weaken the brain circuits that control mood.
How do you treat depression caused by inflammation?
The study on this page points to the dopamine system. Inflammation can affect how the brain makes and releases dopamine. Some patients had major depression and a CRP above 2 mg/L. In them, a single dose of the dopamine precursor L-DOPA strengthened links in the brain’s reward circuit, compared with placebo. The researchers see L-DOPA as a possible treatment for this group, not yet a proven one.
How do doctors measure inflammation in depression?
The study used C-reactive protein, or CRP, a marker measured in the blood. Patients with major depressive disorder were grouped by their CRP levels. Those above 2 mg/L were the high-inflammation group. The benefit of L-DOPA on the reward circuit, and its link to less anhedonia, showed up only in that high-CRP group.
What is anhedonia?
Anhedonia is the inability to feel pleasure. It is a symptom of depression. Dopamine helps control drive, reward and pleasure. That is why the researchers looked at the brain’s reward circuit. In patients with high inflammation, stronger links in the reward circuit after L-DOPA went with lower anhedonia scores.
Which brain chemicals are involved in depression?
Several brain chemicals are involved, including serotonin, norepinephrine and dopamine. Serotonin helps set mood, hunger and sleep. Norepinephrine drives the fight-or-flight response. It keeps you alert and focused. Dopamine runs drive, reward and pleasure. When these chemicals are out of balance, depression may follow. Many antidepressants work by raising serotonin in the brain.
Dr. Gurpreet Singh Padda, MD, MBA, MHP
