New Mechanism Proposed in Antidepressant Effect of Exercise

WASHINGTON — It is widely known that exercise has mental health benefits and can help treat symptoms of depression. There are multiple hypothesized mechanisms behind how it works, and researchers at the University College London have added a new theory to the mix. 

In a new report published in the Translational Psychiatry Journal, researchers lay out their proposed framework for how inflammation, dopamine and motivation may be the link between exercise and depression symptoms. We will give an overview of the new information and what it may mean for the future of exercise as a treatment for depression.

From Movement to Motivation

The paper lays out several ways depression, inflammation, dopamine, motivation and exercise are linked and suggests a leading way in which exercise may have antidepressant effects. 

Depression

Depression often correlates with sadness, but the symptoms go deeper. This paper focuses on the symptoms of anhedonia, fatigue, and cognitive impairment, grouped as “interest-activity.” Living with these symptoms can affect people’s ability to work, socialize and enjoy life.

Motivational Symptoms and Dopamine

A common outcome of the interest-activity symptoms is a lack of motivation. It starts with anhedonia — defined as the inability to feel pleasure. Anhedonia may be caused by a disruption of dopamine. 

Dopamine is a neurotransmitter in the reward center of the brain. People with anhedonia may have impaired reward processing, so they lose motivation because they cannot feel a “reward” after accomplishing a task. Dopamine is well-established to play a role in motivation.

Depression, Dopamine and Inflammation

Much research suggests that the depression symptoms related to motivation may be linked to inflammation. People with depression and anhedonia often have chronic inflammation. Conversely, chronic inflammation is associated with an increased risk of developing depression.

Reducing inflammation for people with chronic inflammation may reduce depression symptoms, including anhedonia. Other research shows that inflammation decreases dopamine activity. In some animal studies, inducing inflammation reduces dopamine and triggers depressive behaviors.

Exercise

The next part of the report examines how these variables (inflammation, dopamine, and depression) intersect with exercise.

Exercise and Depression

It is well established that more physical activity can decrease the odds of developing depression or help to lessen symptoms for people who have depression. 

Potential Mechanisms of Exercise as an Antidepressant

Aside from this new framework, here are a few other potential ways that exercise may have an antidepressant effect:

• Exercise increases BDNF, a protein in the brain that can boost mood and cognition.
• Exercise may decrease oxidative stress.
• Exercise may decrease cortisol (stress hormone) levels.
• Exercise may boost self-esteem and self-efficacy.

Exercise Decreases Inflammation

Research shows that exercise has an anti-inflammatory effect, but only after consistent exercise over a long period. The report points out a difference between the brain’s acute response to exercise (a momentary mood boost) and the long-term effects of repeated exercise throughout a training program. 

Exercise Increases Dopamine

Much research suggests that aerobic exercise, in particular, boosts dopamine transmission. More dopamine may increase motivation, especially for people with anhedonia. The best results are obtained from a long duration of training (weeks, months, and years).

Hypothesis: Reducing Inflammation Creates Space for Dopamine Transmission

The crux of the argument comes here. Depression is associated with low dopamine, low motivation and high inflammation. Exercise can reduce inflammation, boost dopamine transmission and initiate motivation. 

The idea is to put the two together: use exercise to cut down on the inflammation that is worsening depression to clear the way to potentially enhance dopamine.

The report cites an animal study. In the case of inflammation, exercise protects against lost dopamine caused by inflammation, transmits more dopamine and initiates other brain activity. The theory is that it may work this way in humans as well.

Why It Matters

The report highlights a few reasons why this new finding is significant.

• Depression is difficult to treat: Statistics show that fewer than 50% of people who take SSRIs respond to treatment. Anhedonia is highly associated with failed SSRI trials. Antidepressant drugs are often ineffective at treating motivation and may even worsen symptoms. An alternative treatment, like exercise, is essential to find.
• Helping different populations: Not everyone who has depression also has chronic inflammation. However, for those who do, this could be a key finding in prescribing exercise to help reduce inflammation and potentially boost dopamine.
• Exercise has other benefits: It is a cost-effective, scalable, accessible way to treat depression and improves overall physical health (heart, lungs, bones, and muscles). 

Future Studies Ahead

The potential link between inflammation, dopamine, motivation, exercise and depression can spark new research and developments in treating depression. The team behind the paper is running a new trial based on their hypothesis on 250 participants aged 18 to 60. Hopefully, they will get some answers. 

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